The Effect of Fucoidan, a Potential New, Natural, Anti-Neoplastic Agent on Uterine Sarcomas and Carcinosarcoma Cell Lines: ENITEC Collaborative Study
Marcin Bobiński · Karolina Okła · Wiesława Bednarek · Anna Wawruszak · Magdalena Dmoszyńska‑Graniczka · Pablo Garcia‑Sanz · Iwona Wertel · Jan Kotarski
Abstract
The aim of the study was to assess the activity of fucoidan on the uterine sarcomas (MES-SA and ESS-1) and carcinosarcoma cell lines (SK-UT-1 and SK-UT-1B) and its toxicity on the human skin fibroblasts (HSF). Two uterine sarcomas and two carcinosarcoma cell lines were examined, as a control HSF were used. Cell viability was assessed with MTT test, apoptosis with caspase-3 activity and cell cycle by assessment of DNA synthesis. Fucoidan significantly decreases cell viability in SK-UT-1, SK-UT-1B, and ESS-1 cell lines, such effect was not observed in MES-SA. Fucoidan was not substantially affecting proliferation among normal cells. The tested agent induced apoptosis in all cell cultures used in the experiment. Fucoidan affects cell cycle of all tested cell lines except MES-SA by increasing percentage of cells in G0/sub-G1/G1 phase. Fucoidan do not only affect proliferation but induces apoptosis in selected uterine sarcoma and carcinosarcoma cell lines, so it has potential to be used as cytotoxic agent. Fucoidan seems to be promising anti-cancer agent for endometrial stromal sarcoma and carcinosarcoma.
Keywords Uterine sarcomas · Fucoidan · Targeted treatment
The Expression of the SLIT–ROBO Family in Adult Patients with Acute Myeloid Leukemia
Aleksandra Gołos · Dorota Jesionek‑Kupnicka · Lidia Gil · Marcin Braun · Mieczyslaw Komarnicki · Tadeusz Robak · Agnieszka Wierzbowska
Abstract
Introduction SLIT–ROBO is a ligand–receptor family of neuronal guidance cues that has been involved in pathological and physiological angiogenesis. SLIT–ROBO expression is altered in many tumours. However, no data exist about the role of the whole family in acute myelogenous myeloid leukemia (AML). Purpose Herein, we assessed the expression of all SLIT–ROBO family in bone marrow (BM) biopsy of AML patients and control group on both protein and RNA levels. Methods The paraffin-embedded tissue blocks were subjected to immunohistochemistry for SLIT1, SLIT2, SLIT3, ROBO1, ROBO2, ROBO3, and ROBO4. Microvessel density (MVD) was evaluated by CD34 immunohistochemistry. An in silico analysis using The Cancer Genome Atlas data repository was conducted for assessment of RNA level. Results Acute myeloid leukemia patients were generally high expressers of ROBO1 and ROBO2 compared to the controls (p < 0.0001, p < 0.001, respectively). In contrast, low expression of SLIT1, SLIT2, and SLIT3 ligands has been noted more commonly in AML than in control BM samples (p < 0.0001, p = 0.003, and p = 0.001, respectively). ROBO4 expression correlated with MVD. The in silico analysis showed a poor prognostic value of high ROBO3 and low SLIT2 RNA levels (p = 0.0003 and p = 0.0008, respectively), as well as high ROBO3 and ROBO4 RNA levels in cytogenetic poor risk groups of patients (p = 0.0029 and p = 0.0003, respectively). Conclusions These data indicate that SLIT–ROBO family members play a role in the biology of AML. Low expression of SLIT in BM of AML patients may suggest its expression alterations in AML. Increased expression of ROBO1 and ROBO2 in AML patients suggests their participation in AML pathogenesis.
Keywords SLIT protein · ROBO protein · Angiogenesis · Acute myeloid leukemia · Nerve tissue proteins
Theaflavin-3, 3′-Digallate Attenuates Rheumatoid Inflammation
in Mice Through the Nuclear Factor-κB and MAPK Pathways
Wenshu Liu1 · Jingying Li1
Received: 8 August 2018 / Accepted: 18 February 2019 / Published online: 14 March 2019
© L. Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland 2019
Abstract
Rheumatoid arthritis (RA) is a common autoimmune disease which impacts a large number of patients worldwide, and new
drugs are required for lower the disease burden. Theaflavin-3, 3′-digallate (TFDG) is polyphenol exhibiting inhibition on
inflammatory factors. This study aimed to explore the attenuation of TFDG on RA. The collagen-induced arthritis (CIA)
mouse model was established and administered with TFDG. The arthritis score and incidence was recorded to assess the
amelioration of TFDG on arthritis. Histopathological change of the mouse joint tissues was evaluated by haemotoxylin and
eosin staining. The expression of pro-inflammatory mediators including interleukin (IL)-1β, tumor necrosis factor (TNF)-α,
and IL-6 was quantified by ELISA. The activation of nuclear factor (NF)-κB and mitogen-activated protein kinase (MAPK)
signaling pathways in the synovium were determined by Western blotting. In comparison with the control, administration
of TFDG significantly reduced arthritis score and incidence in the CIA mouse model. TFDG significantly suppressed the
expression of IL-1β, TNF-α, and IL-6, as well as the levels of MMP-1, MMP-2, and MMP-3 in the synovium. TFDG also
showed remarkable inhibition on the activation of NF-κB and the phosphorylation of P38, JNK2, and ERK. This study puts
up evidence that TFDG exerts protection on RA via inhibiting the activation of NF-κB- and MAPK-signaling pathways.
Keywords Rheumatoid arthritis · Theaflavin-3 · 3′-digallate · Collagen-induced arthritis model · Nuclear factor-kappa B ·
MAPK pathway
Natural Killer and Natural Killer T Cells in Juvenile Systemic Lupus
Erythematosus: Relation to Disease Activity and Progression
Asmaa M. Zahran1 · Mona H. Abdel‑Rahim2 · Khalid I. Elsayh3 · Manal M. Hassanien4 · Safaa A. Mahran4 ·
Helal F. Hetta2,5
Received: 3 November 2018 / Accepted: 14 March 2019 / Published online: 4 April 2019
© L. Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland 2019
Abstract
The contribution of innate immune cells, including natural killer (NK) and natural killer T (NKT) cells, in systemic lupus
erythematosus (SLE) is still unclear. Herein, we examined the frequency of peripheral NK cells, CD56dim and CD56bright
NK cells, and NKT cells in patients with juvenile SLE and their potential relations to SLE-related clinical and laboratory
parameters. The study included 35 SLE children and 20 apparently healthy controls. After baseline clinical and lab work,
SLE Disease Activity Index (SLEDAI-2K) and Pediatric Systemic Lupus International Collaborative Clinics/American Col-
lege of Rheumatology (SLICC/ACR) Damage Index (Ped-SDI) scores were assessed. The frequency of peripheral NK cells,
CD56dim and CD56bright NK cells, and NKT cells was examined using flow cytometry. SLE patients showed significantly
lower frequency of NK cells and NKT cells and higher frequency of CD56bright NK cells compared to controls. Disease
activity, urea, and creatinine correlated negatively with NK, but positively with CD56bright NK cells. NK and NKT cells
exhibited inverse correlation with the renal biopsy activity index; however, CD56bright NK cells showed direct correlations
with both activity and chronicity indices. Regarding Ped-SDI, renal, neuropsychiatry disorders, and growth failure corre-
lated inversely with NK but directly with CD56bright NK cells. NKT cell inversely correlated with renal damage and delayed
puberty. In conclusion, low frequency of NK and NKT and expansion of CD56bright NK cells are marked in juvenile SLE,
particularly with activity. These changes have direct effect on renal impairment and growth failure, reflecting their potential
influence on disease progression.
Keywords NK cells · NKT cells · SLE
Heterogeneous Mixture of Amniotic Cells is Likely a Better Source
of Stem Cells than Adipose Tissue
Diana Kitala1,2,3 · Agnieszka Klama‑Baryła1,3 · Marcelina Misiuga1 · Wojciech Łabuś1,2 · Małgorzata Kraut1 ·
Michał Szapski1 · Marta Lesiak4 · Daniel Krakowian4 · Aleksander L. Sieroń4 · Marek J. Łos5,6 ·
Marek Kucharzewski7
Received: 26 November 2018 / Accepted: 14 March 2019 / Published online: 16 April 2019
© The Author(s) 2019
Abstract
Stem cells are increasingly being used in the course of burn treatment. As several different types of stem cells are available for the
purposes, it is important to chose the most efficient and the most practicable stem cell type. The aim of this study was to compare
the potential of heterogeneous amnion cell mixture with the presently used standard therapy, the adipose tissue-derived stem
cells. The placenta was collected during a Cesarean section procedure. Adipose tissue tissue-derived cells were isolated using the
Cytori’s Celution® System. Cells were tested for fulfillment of the minimum criteria for stem cells. The efficiency of cell cultures
was tested by an analysis of population doubling, cell proliferation, cell cycle and cell migration. Amniotic cells presented a higher
ability for differentiation to chondrocytes and osteocytes than adipose-derived regenerative cells but a lower ability for differentia-
tion toward adipocytes. Additionally, in vitro experiments have demonstrated a higher applicability of amniotic cells than adipose
tissue-derived stem cells. Amniotic cells show several advantages: easy access to placenta, low costs and a lack of ethical dilemmas
related to stem cell harvesting. The main disadvantage is, however, their availability, as isogenic treatment would only be possible
for women around children-bearing age, unless personalized banks for amniotic cells would be established.
Keywords Stem cells · Amniotic membrane cells · Adipose tissue cells · Burn treatment
PD-L1 Ameliorates Murine Acute Graft-Versus-Host Disease
by Suppressing Effector But Not Regulatory T Cells Function
Lin Tang1,2,3,4 · Shoubao Ma1,2,4 · Huanle Gong1,2,4 · Jun Wang1,2,4 · Yang Xu1,2,3,4 · Depei Wu1,2,4 · Aining Sun1,2,4
Received: 19 September 2018 / Accepted: 18 March 2019 / Published online: 29 March 2019
© L. Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland 2019
Abstract
There is increasing evidence that interaction between programmed death 1 (PD-1) and its ligands PD-1 (PD-L1) plays a
critical role in the pathology of acute graft-versus-host disease (aGVHD). However, the role of PD-L1 in the development of
aGVHD has been controversial in recent mouse studies. In this study, we carried out studies in a murine aGVHD model to
clarify the role of PD-L1 in aGVHD pathogenesis. We found that systemic overexpression of PD-L1 by hydrodynamic gene
transfer (HGT) method in vivo ameliorates aGVHD-induced lethality in mice. Systemic overexpression of PD-L1 inhibits
the donor T cells activation, effector memory status, as well as Th1 and Th17 cells responses in vivo. In addition, PD-L1 Ig
treatment significantly suppressed T cells’ proliferation, promoted T cells’ apoptosis, and reduced pro-inflammatory cytokines
expression by effector T cells in vitro in the stimulation of anti-CD3/CD28 and allogeneic dendritic cells. However, we found
that PD-L1 overexpression did not affect Treg cells’ differentiation in vivo and in vitro, depletion of Treg cells in PD-L1
HGT recipients did not aggravate aGVHD mortality. Therefore, our results demonstrated that systemic treatment with PD-L1
protein ameliorates aGVHD by suppressing effector but not regulatory T cell function. Our findings suggest that systemic
treatment with PD-L1 may be a potential strategy to prevent or ameliorate aGVHD.
Keywords PD-1 · PD-L1 · aGVHD · Treg cells
Significance and Role of Pattern Recognition Receptors in Malignancy
Jan Żeromski1 · Mariusz Kaczmarek1 · Maciej Boruczkowski1 · Agata Kierepa2 · Arleta Kowala‑Piaskowska2 ·
Iwona Mozer‑Lisewska2
Received: 10 September 2018 / Accepted: 19 March 2019 / Published online: 11 April 2019
© The Author(s) 2019
Abstract
Pattern recognition receptors (PRRs) are members of innate immunity, playing pivotal role in several immunological reac-
tions. They are known to act as a bridge between innate and adaptive immunity. They are expressed on several normal cell
types but have been shown with increasing frequency on/in tumor cells. Significance of this phenomenon is largely unknown,
but it has been shown by several authors that they, predominantly Toll-like receptors (TLRs), act in the interest of tumor, by
promotion of its growth and spreading. Preparation of artificial of TLRs ligands (agonists) paved the way to use them as a
therapeutic agents for cancer, so far in a limited scale. Agonists may be combined with conventional anti-cancer modalities
with apparently promising results. PRRs recognizing nucleic acids such as RIG-1 like receptors (sensing RNA) and STING
(sensing DNA) constitute a novel promising approach for cancer immunotherapy.
Keywords PRRs · TLRs · Cancer cells · Agonists · Nucleic-acid sensing · RLRs · cGAS-STING pathway
Post‑transplant Alternative Complement Pathway Activation
Influences Kidney Allograft Function
Dorota Bartoszek1 · Oktawia Mazanowska1,2 · Katarzyna Kościelska‑Kasprzak1 · Agnieszka Lepiesza3 ·
Marta Myszka1 · Marcelina Żabińska1 · Magdalena Krajewska1 · Marian Klinger1
Received: 30 May 2018 / Accepted: 29 March 2019 / Published online: 26 April 2019
© The Author(s) 2019
Abstract
The complement system is one of the crucial pathophysiological mechanisms that directly influence the function of a trans-
planted kidney. Since the complement pathways’ activation potential can be easily determined via their functional activity
measurement, we focused on fluctuation in the cascade activity in the early post-transplant period. The aim of the study was
to relate the kidney transplantation-induced complement system response to allograft outcome. Forty-two kidney recipients
(aged: 53.5 [37–52], 17 females/25 males) and 24 healthy controls (aged: 40.5 [34–51], 13 females/11 males) were enrolled
in the study. The functional activities of alternative, classical, and lectin pathways were determined before and in the first
week after transplantation using Wielisa®-kit. We observed that the baseline functional activity of the alternative pathway
(AP) was higher in chronic kidney disease patients awaiting transplantation compared to healthy controls and that its level
depended on the type of dialysis. AP-functional activity was decreased following transplantation procedure and its post-
transplant level was related to allograft function. The baseline and transplantation-induced functional activities of the clas-
sical and lectin pathways were not influenced by dialysis type and were not associated with transplant outcome. Moreover,
our study showed that intraoperative graft surface cooling had a protective effect on AP activation. Our study confirms the
influence of dialysis modality on persistent AP complement activation and supports the role of AP in an early phase after
kidney transplantation and allograft outcome.
Keywords Alternative pathway · Functional complement activity · Kidney transplantation · Kidney recipients
Conjugation of Meningococcal Lipooligosaccharides Through Their
Non‑Reducing Terminus Results in Improved Induction a Protective
Immune Response
Małgorzata Mieszała1 · Harold J. Jennings2 · Marek Drab1 · Andrzej Gamian1
Received: 25 September 2018 / Accepted: 5 April 2019 / Published online: 27 April 2019
© The Author(s) 2019
Abstract
The present studies prove that conjugation of meningococcal lipooligosaccharides through their non-reducing terminus
conserves their inner epitopes resulting in conjugates potent to induce a protective immune response. Four different oligo-
saccharides were obtained by specific degradations of the same L7 lipooligosaccharide (L7-LOS), and each was linked to
tetanus toxoid by direct reductive amination. Two were truncated oligosaccharides with incomplete inner epitopes and were
obtained by mild acid hydrolysis of lipooligosaccharide. The terminal galactose of one oligosaccharide was additionally
enzymatically oxidized. These oligosaccharides were conjugated through a newly exposed terminal Kdo in reducing end
or through oxidized galactose localized at non-reducing end of the core, respectively. The third was a full-length oligosac-
charide obtained by O-deacylation of the L7-LOS and subsequent enzymatic removal of phosphate substituents from its
lipid A moiety. The fourth one was also a full-length O-deacylated lipooligosaccharide, but treated with galactose oxidase.
This allowed direct conjugation to tetanus toxoid through terminal 2-N-acyl-2-deoxy-d-glucopyranose or through oxidized
galactose, respectively. Comparison of the immune performance of four conjugates in mice revealed, that while each was
able to induce significant level of L7-LOS-specific IgG antibody, the conjugates made with the full-length saccharides were
able to induce antibodies with increased bactericidal activity against homologous meningococci. Only full-length oligosac-
charides were good inhibitors of the binding of L7-LOS to the bactericidal antiserum. Moreover, induction of the significant
level of the L7-LOS-specific antibody by full-length lipooligosaccharide conjugated from non-reducing end, provided also
the direct evidence that internal core epitopes are fully responsible for the immunorecognition and immunoreactivity.
Keywords Meningococcal lipooligosaccharides · Conjugate vaccines · Immunological properties
The Influence of Antidepressants on the Immune System
Łukasz P. Szałach1 · Katarzyna A. Lisowska1 · Wiesław J. Cubała2
Received: 27 November 2018 / Accepted: 10 April 2019 / Published online: 29 April 2019
© The Author(s) 2019
Abstract
Depression is one of the most frequently diagnosed condition in psychiatry. Despite the availability of many preparations,
over 30% of treated patients do not achieve remission. Recently the emphasis is put on the contribution of the body’s inflam-
matory response as one of the causes of depression. The interactions between nervous and immune systems are the main
issue addressed by psychoneuroimmunology. In patients suffering from depression changes in the plasma concentrations
of cytokines and in the number and level of activation of immune cells has been found. Attention is paid to the high levels
of pro-inflammatory cytokines, the prevalence of Th1 responses to Th2, weakening of NK cell cytotoxicity and changes in
lymphocyte proliferation and apoptosis. A number of studies focus on influence of antidepressants and non-standard methods
of depression treatment, such as ketamine infusion, on patients’ immunology. Many of them seem to regulate the immune
responses. The study results encourage to look for new ways to treat depression with immunomodulatory drugs. In this article
authors present the current knowledge about immune system changes accompanying depression as well as the study results
showing the influence of drugs on the immune system, especially in the context of reducing the symptoms of depression.
Keywords Depression · Antidepressants · Lymphocytes · Cytokines · Proliferation · Apoptosis
Visfatin Plays a Significant Role in Alleviating
Lipopolysaccharide‑Induced Apoptosis and Autophagy Through PI3K/
AKT Signaling Pathway During Acute Lung Injury in Mice
Xin‑Tong Wu1 · Abdur Rahman Ansari2 · Xin‑Xin Pang1 · Hui‑Zhen Li1 · Zhe‑Wei Zhang1 · You Luo1 ·
Muhammad Arshad3 · Hui Song1
Received: 3 September 2018 / Accepted: 24 April 2019 / Published online: 29 May 2019
© L. Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland 2019
Abstract
Visfatin is involved in the body’s inflammation and immune response. Inflammation could promote, while visfatin may
directly or indirectly mitigate the effects of apoptosis and autophagy. Whether visfatin lessens the detrimental effects of
lipopolysaccharide (LPS)-induced mouse acute lung injury (ALI) is poorly understood yet. Therefore, in the current study,
the regulation mechanism of visfatin on apoptosis and autophagy was explored in Kunming mice by replicating LPS-induced
inflammatory ALI model. Based on the mouse model of ALI, HE staining, TUNEL, transmission electron microscopy,
immunohistochemical staining, real-time fluorescence quantitative PCR and western blot were used and the results showed
that the alveolar septum was thinner than that of the LPS group, slight lung interstitial and alveolar exudation appeared, and a
small number of inflammatory cell infiltration was found in the visfatin intervention group, indicating reduced tissue damage
in lungs. After visfatin treatment, the expression of pro-apoptotic genes Bax, Bik, and p53 decreased and the expression of
anti-apoptotic genes Bcl-2 and Bcl-xl increased, and expression of autophagy factors LC3 and Beclin1 decreased, indicating
that visfatin inhibits apoptosis and reduces autophagy. The expression of PI3K and p-AKT was upregulated in the visfatin
intervention group, the expression of AKT was downregulated, and the PI3K/AKT signaling pathway was activated. Hence,
visfatin could activate the PI3K/AKT signaling pathway, reduce the apoptotic rate in alveolar epithelial cells and the level
of autophagy in ALI by regulating the expression of autophagy factors, ultimately causing a protective effect on lung tissue.
Keywords Visfatin · Acute lung injury · Apoptosis · Autophagy · PI3K/AKT signaling pathway
IgG from Non‑atopic Individuals Induces In Vitro IFN‑γ and IL‑10
Production by Human Intra‑thymic γδT Cells: A Comparison
with Atopic IgG and IVIg
Ludimila Souza Santos1 · Fábio da Ressureição Sgnotto2 · Amanda Harumi Sabô Inoue1 ·
Archangelo Fernandes Padreca3 · Ricardo Palamar Menghini3 · Alberto José da Silva Duarte1,4 ·
Jefferson Russo Victor1,3
Received: 14 January 2019 / Accepted: 27 April 2019 / Published online: 13 May 2019
© L. Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland 2019
Abstract
Matured in the thymus, γδT cells can modulate the development of allergy in humans. The main γδT cell subsets have
been described as interleukin (IL)-17A or interferon (IFN)-γ producers, but these cells can also produce other modulatory
cytokines, such as IL-4 and IL-10. Here, we aimed to evaluate whether IgG can modulate the profile of cytokine production
by γδT cells during their maturation in the thymus and after its migration to peripheral tissues. Thymic tissues were obtained
from 12 infants, and peripheral blood mononuclear cells (PBMCs) were obtained from adults (both groups without an atopic
background). IgG was purified from atopic and non-atopic volunteers. Thymocytes and PBMCs were cultured with purified
atopic or non-atopic IgG, and intracellular cytokine production and phenotype were assessed. Mock and IVIg conditions
were used as controls. IgG from non-atopic individuals induced IFN-γ and IL-10 production by thymic γδT cells, and no
effect was observed on peripheral γδT cells. IL-17 production was inhibited by non-atopic IgG on thymic γδT cells and
augmented by atopic IgG on peripheral γδT cells. Modulated thymic γδT cells did not produce IFN-γ and IL-10 simultane-
ously. We additionally evaluated the phenotype of intrathymic γδT cells and observed that IgG from all groups could induce
CD25 expression and could not influence the CD28 expression of these cells. This report describes evidence revealing that
IgG may influence the production of IFN-γ and IL-10 by intrathymic γδT cells depending on the donor atopic state. This
observation is unprecedented and needs to be considered in further studies in the IgG immunotherapy field.
Keywords Allergy · IgG · IFN-γ · IL-10 · γδT cells · Thymus
Proportion of Cytotoxic Peripheral Blood Natural Killer Cells and T‑Cell
Large Granular Lymphocytes in Recurrent Miscarriage and Repeated
Implantation Failure: Case–Control Study and Meta‑analysis
Kamila Kolanska1 · Ludovic Suner2 · Jonathan Cohen1 · Yasmine Ben Kraiem1 · Leo Placais3 · Olivier Fain3 ·
Marie Bornes1 · Lise Selleret1 · François Delhommeau2 · Frédéric Feger2 · Emmanuelle Mathieu d’Argent1 ·
Emile Darai1 · Nathalie Chabbert‑Buffet1 · Jean‑Marie Antoine1 · Gilles Kayem5 · Arsène Mekinian3,4
Received: 22 November 2018 / Accepted: 11 May 2019 / Published online: 30 May 2019
© L. Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland 2019
Abstract
We aimed to compare the proportion of peripheral blood natural killer (NK) cells (CD3–CD56+) and T-cell large granular
lymphocytes (CD8+CD57+) during preconception in a homogenous group of women with unexplained well-defined recur-
rent miscarriage (RM) and repeated implantation failure (RIF) vs healthy controls in relation to pregnancy outcomes. This
case–control study followed by a literature review and meta-analysis was conducted in three university hospitals. Patients
and controls were consecutively recruited from December 2015 to October 2017. In total, 115 women were included in the
study: 54 with RM, 41 with RIF and 20 healthy controls with ≥ 2 term births. Percentages of CD3–CD56+ and CD8+CD57+
cells and sub-populations of CD3–CD56+ cells did not differ between cases and controls. The results for women with sub-
sequent miscarriage did not differ from those with live births. The meta-analysis of the literature showed higher NK-cell
proportions in RM [mean difference 3.47 (95% CI 2.94–4.00); p < 0.001] and RIF [mean difference 1.64 (95% CI 0.82–2.45);
p < 0.001] than controls. However, the heterogeneity between the different studies was high. The proportion of peripheral
blood CD3–CD56+ and CD8+CD57+ cells in the preconception period does not reflect the risk of implantation failure or
miscarriage and should not be recommended indicators for the management of RM and RIF. Further prospective large stud-
ies are needed to develop a reliable peripheral blood marker of immune deregulation.
Keywords Natural killer cells · NK · T-cell large granular lymphocytes · T-LGL · Recurrent miscarriage · Recurrent
implantation failure · RIF · Pregnancy outcome
MicroRNAs: Potential Biomarkers and Targets of Therapy in Allergic
Diseases?
Krzysztof Specjalski1 · Ewa Jassem1
Received: 12 January 2019 / Accepted: 13 May 2019 / Published online: 28 May 2019
© The Author(s) 2019
Abstract
MicroRNAs (miRNAs) are small non-coding RNA molecules that are 18–22 nucleotides long and highly conserved through-
out evolution. Currently, they are considered one of the fundamental regulatory mechanisms of genes expression. It has
been demonstrated that miRNAs are involved in many biologic processes, such as signal transduction, cell proliferation
and differentiation, apoptosis and stress responses. More recently, the role of miRNA has also been revealed in numerous
immunological and inflammatory disorders, including allergic inflammation. Specific miRNA profiles were demonstrated
in asthma, allergic rhinitis and atopic dermatitis. A core set of miRNAs involved in atopic diseases include upregulated
miR-21, miR-223, miR-146a, miR-142-5p, miR-142-3p, miR-146b, miR-155 and downregulated let-7 family, miR-193b and
miR-375. Most of the involved miRNAs increase secretion of Th2 cytokines (miR-1248, miR-146b), decrease secretion of
Th1 cytokines (miR-513-5p, miR-625-5p) or promote differentiation of T cells towards Th2 (miR-21, miR-19a). In asthma
miR-140-3p, miR-708 and miR-142-3p play a role in hyperplasia and hypertrophy of bronchial smooth muscle cells. Some
single miRNAs or, more probably, their sets hold the promise for their use as biomarkers of atopic diseases. They are also
promising target of future therapies.
Keywords miRNA · Allergy · Asthma · Allergic rhinitis · Atopic dermatitis
CTLA‑4 Expression Inversely Correlates with Kidney Function
and Serum Immunoglobulin Concentration in Patients with Primary
Glomerulonephritides
Ewelina Grywalska1 · Iwona Smarz‑Widelska2 · Sebastian Mertowski1 · Krzysztof Gosik1 · Michał Mielnik3 ·
Martyna Podgajna1 · Monika Abramiuk4 · Bartłomiej Drop5 · Jacek Roliński1 · Wojciech Załuska6
Received: 6 April 2019 / Accepted: 21 May 2019 / Published online: 8 June 2019
© The Author(s) 2019
Abstract
Major causes of chronic kidney disease are primary proliferative and nonproliferative glomerulonephritides (PGN and
NPGN). However, the pathogenesis of PGN and NPGN is still not fully understood. Cytotoxic T-lymphocyte-associated
antigen-4 (CTLA-4) is a T-cell membrane receptor that plays a key role in T-cell inhibition. Despite its role in autoimmu-
nological diseases, little is known about the involvement of CTLA-4 in the pathogenesis of PGN and NPGN. The objective
of this study was to determine the role of CTLA-4 in the pathogenesis of PGN and NPGN by evaluating the frequencies
of T and B lymphocytes expressing CTLA-4 and the serum concentration of the sCTLA-4 isoform in patients with PGN
and NPGN in relation to clinical parameters. The study included peripheral blood (PB) samples from 40 PGN and NPGN
patients and 20 healthy age- and sex-matched volunteers (control group). The viable PB lymphocytes were labeled with
fluorochrome-conjugated monoclonal anti-CTLA-4 antibodies and analyzed using flow cytometry. The serum concentration
of sCTLA-4 was measured using ELISA. The frequencies and absolute counts of CD4+/CTLA-4+ T lymphocytes, CD8+/
CTLA-4+ T lymphocytes and CD19+/CTLA-4+ B lymphocytes and the serum sCTLA-4 concentration were lower in PGN
and NPGN patients that in the control group. Reduced sCTLA-4 expression was associated with a lower concentration of
serum immunoglobulins. Our results indicate that deregulation of CTLA-4 expression may result in continuous activation
of T cells and contribute to the pathogenesis of PGN and NPGN.
Keywords Cytotoxic T-lymphocyte-associated antigen-4 · Glomerulonephritides, kidney function
Diverse Activity of IL‑17+ Cells in Chronic Skin and Mucosa
Graft‑Versus‑Host Disease
Aleksandra Klimczak1 · Krzysztof Suchnicki2 · Mariola Sedzimirska2 · Andrzej Lange1,2
Received: 5 November 2018 / Accepted: 30 May 2019 / Published online: 8 June 2019
© The Author(s) 2019
Abstract
Excessive inflammatory environment in a course of chronic graft-versus-host disease (cGvHD) is associated with T-cell
trafficking into inflamed tissues. This study focused on the identification of IL-17-producing cells in the tissue biopsies of
cGvHD patients. Forty-one biopsy specimens of cGvHD lesions of the skin (n = 27), gastrointestinal tract (n = 9) and oral
mucosa (n = 5), examined in 24 patients, were morphologically defined according to the NIH criteria and analyzed for the
presence of cellular infiltrations including: IL-17+, FOXP3+ and CCR6+ cells. IL-17+ cells were identified in 26/27 skin and
in all gut and oral mucosa biopsies, being more frequent in mucosa lesions than in the skin (11/14 vs 14/26, respectively;
NS: not significant). Double staining documented that CD138+/IL-17+ cells were commonly seen in the gut than in the skin
(5/8 vs 3/11, respectively; NS). In the skin, cells expressing trafficking receptor CCR6+ were more frequent than IL-17+
cells compared to the mucosa (23/26 vs 2/13, respectively; p < 0.0001). CCR6 was present on a majority of IL-17+ cells in
all examined skin biopsies but only in 6 out of 11 digestive tract biopsies (p = 0.0112). FOXP3+ cells were identified only
in five patients (with mild lesions) at least in one biopsy. In this study group, results documented that local expansion of
IL-17-producing cells in the digestive tract correlate with moderate and severe clinical symptoms of cGvHD, in contrast to
the skin, where IL-17+ cells are rather scarcely present (p = 0.0301) and the course of cGvHD is slowly progressing with
final organ deterioration.
Keywords Graft-versus-host disease · Chronic GvHD · IL-17-producing cells · Skin and mucosa
Variant and Specific Forms of Autoimmune Cholestatic Liver Diseases
George N. Dalekos1,2 · Nikolaos K. Gatselis1,2
Received: 27 January 2019 / Accepted: 31 May 2019 / Published online: 5 June 2019
© L. Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland 2019
Abstract
Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are the main autoimmune cholestatic liver dis-
eases. IgG4-associated sclerosing cholangitis is another distinct immune-mediated cholestatic disorder of unknown aetiology
that is frequently associated with autoimmune pancreatitis or other IgG4-related diseases. Although the majority of PBC
and PSC patients have a typical presentation, there are common and uncommon important variants or specific subgroups
that observed in everyday routine clinical practice. In this updated review, we summarize the published data giving also our
own experience on the variants and specific groups of autoimmune cholestatic liver diseases. Actually, we give in detail the
underlining difficulties and the rising dilemmas concerning the diagnosis and management of these special conditions in the
clinical spectrum of autoimmune cholestatic liver diseases including the IgG4-associated sclerosing cholangitis highlighting
also the uncertainties and the potential new eras of the research agenda.
Keywords Primary biliary cholangitis · Primary sclerosing cholangitis · Antimitochondrial antibodies · Autoimmune
hepatitis · Autoimmune liver diseases · Variant syndromes
Adjuvant Allergen Fusion Proteins as Novel Tools for the Treatment
of Type I Allergies
Frank Blanco‑Pérez1 · Garibald Papp1 · Alexandra Goretzki1 · Tobias Möller1 · Martina Anzaghe2 · Stefan Schülke1
Received: 27 February 2019 / Accepted: 13 June 2019 / Published online: 20 June 2019
© L. Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland 2019
Abstract
While acute allergic symptoms can be managed by emergency medication, to date, allergen-specific immunotherapy (SIT)
with allergen extracts is the only available curative treatment option. However, the risk of anaphylactic reactions, long treat-
ment duration, varying extract quality, and underrepresentation of certain allergens currently prevent many patients from
successfully undergoing SIT. Novel strategies are needed to enhance efficacy, safety, and convenience of allergy treatment.
Fusion proteins combining allergen and adjuvant into a single molecule can efficiently induce immune responses by targeting
the allergen to the relevant immune cells in vivo. Simultaneous co-delivery of both antigen and adjuvant to the same cell in
a fixed molecular ratio triggers the uptake and presentation of the conjugated allergen in the context of the adjuvant-induced
immune cell activation. This review summarizes the published strategies to improve the treatment of type I allergies using
fusion proteins consisting of allergen (peptides) and either (1) immune-activating bacterial (flagellin, MPLA, S-layer, chol-
era-, and tetanus toxin), (2) viral (PreS, VP-1, TAT), or (3) fungal (FIP-fve) components, (4) immune-activating DNA motifs,
(5) forced delivery of allergens to the MHC-II loading pathway, and (6) killing of immune cells expressing allergen-specific
IgE by fusion of the allergen to diphtheria toxin.
Keywords Fusion protein · Allergen · SIT · PAMP · PRR
Role of Macrophages in Pregnancy and Related Complications
Manoj K. Jena1,2 · Neha Nayak1 · Kang Chen1 · Nihar R. Nayak1
Received: 14 December 2018 / Accepted: 28 June 2019 / Published online: 8 July 2019
© L. Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland 2019
Abstract
Macrophages (MФs) are the leukocytes produced from differentiation of monocytes and are located in almost all tissues of
human body. They are involved in various processes, such as phagocytosis, innate and adaptive immunity, proinflammatory
(M1) and anti-inflammatory (M2) activity, depending on the tissue microenvironment. They play a crucial role in pregnancy,
and their dysfunction or alteration of polarity is involved in pregnancy disorders, like preeclampsia, recurrent spontaneous
abortion, infertility, intrauterine growth restriction, and preterm labor. About 50–60% of decidual leukocytes are natural killer
(NK) cells followed by MФs (the second largest population). MФs are actively involved in trophoblast invasion, tissue and
vascular remodeling during early pregnancy, besides their role as major antigen-presenting cells in the decidua. These cells
have different phenotypes and polarities in different stages of pregnancy. They have also been observed to enhance tumor
growth by their anti-inflammatory activity (M2 type) and prevent immunogenic rejection. Targeted alteration of polarity
(M1–M2 or vice versa) could be a major focus in the future treatment of pregnancy complications. This review is focused on
the role of MФs in pregnancy, their involvement in pregnancy disorders, and decidual MФs as possible therapeutic targets
for the treatment of pregnancy complications.
Keywords Macrophage · Human pregnancy · Decidualization · Polarity · VEGF · Preeclampsia
Induction of Chronic Subclinical Systemic Inflammation
in Sprague–Dawley Rats Stimulated by Intermittent Bolus Injection
of Lipopolysaccharide
Yazan Ranneh1 · Abdah Md. Akim2 · Hasiah Ab. Hamid2 · Huzwah Khazaai2 · Norhafizah Mokhtarrudin3 ·
Abdulmannan Fadel4 · Mohammed H. K. Albujja2,5
Received: 27 June 2018 / Accepted: 29 June 2019 / Published online: 5 July 2019
© L. Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland 2019
Abstract
Chronic subclinical systemic inflammation has a key role in stimulating several chronic conditions associated with cardio-
vascular diseases, cancer, rheumatoid arthritis, diabetes, and neurodegenerative diseases. Hence, developing in vivo models
of chronic subclinical systemic inflammation are essential to the study of the pathophysiology and to measure the immu-
nomodulatory agents involved. Male Sprague–Dawley rats were subjected to intraperitoneal, intermittent injection with
saline, or lipopolysaccharide (LPS) (0.5, 1, 2 mg/kg) thrice a week for 30 days. Hematological, biochemical, and inflamma-
tory mediators were measured at different timepoints and at the end of the study. The hearts, lungs, kidneys, and livers were
harvested for histological evaluation. Significant elevation in peripheral blood leukocyte includes neutrophils, monocytes,
and lymphocytes, as well as the neutrophils-to-lymphocyte ratio. The pro-inflammatory mediator levels [C-reactive protein,
tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β, and IL-8] along with the biochemical profile (alkaline phosphatase,
aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, creatine kinase, creatinine, and urea)
were increased significantly (P < 0.05) and increased the expression of monocyte chemoattractant protein-1 and TNF-β. The
histopathological changes of heart, lung, kidney, and liver tissues revealed degeneration, cellular infiltration of leukocyte in
the inflammatory foci and interstitial space, edema, early signs of fibrosis, apoptosis, and necrosis. In conclusion, these results
indicate that intermittent exposure to LPS produces chronic subclinical systemic inflammation in multiple organs leading
to chronic conditions and supports this model to be a useful preclinical tool for developing immunotherapeutic agents that
could prevent, or reduce, chronic inflammatory diseases associated with, or without, bacterial translocation.
Keywords Animal model · Chronic diseases · Cytokines · Lipopolysaccharide · Multiple organs · Systemic low-grade
inflammation
Mitochondrial Heat Shock Response Induced by Ectromelia Virus
is Accompanied by Reduced Apoptotic Potential in Murine L929
Fibroblasts
Zbigniew Wyżewski1,2 · Karolina P. Gregorczyk‑Zboroch1 · Matylda B. Mielcarska1 ·
Magdalena Bossowska‑Nowicka1 · Justyna Struzik1 · Joanna Szczepanowska3 · Felix N. Toka4 ·
Marek G. Niemiałtowski1 · Lidia Szulc‑Dąbrowska1
Received: 8 November 2018 / Accepted: 9 July 2019 / Published online: 19 July 2019
© The Author(s) 2019
Abstract
Poxviruses utilize multiple strategies to prevent activation of extrinsic and intrinsic apoptotic pathways for successful rep-
lication. Mitochondrial heat shock proteins (mtHsps), especially Hsp60 and its cofactor Hsp10, are engaged in apoptosis
regulation; however, until now, the influence of poxviruses on mtHsps has never been studied. We used highly infectious
Moscow strain of ectromelia virus (ECTV) to investigate the mitochondrial heat shock response and apoptotic potential in
permissive L929 fibroblasts. Our results show that ECTV-infected cells exhibit mostly mitochondrial localization of Hsp60
and Hsp10, and show overexpression of both proteins during later stages of infection. ECTV infection has only moderate
effect on the electron transport chain subunit expression. Moreover, increase of mtHsp amounts is accompanied by lack of
apoptosis, and confirmed by reduced level of pro-apoptotic Bax protein and elevated levels of anti-apoptotic Bcl-2 and Bcl-
xL proteins. Taken together, we show a positive relationship between increased levels of Hsp60 and Hsp10 and decreased
apoptotic potential of L929 fibroblasts, and further hypothesize that Hsp60 and/or its cofactor play important roles in main-
taining protein homeostasis in mitochondria for promotion of cell survival allowing efficient replication of ECTV.
Keywords ECTV · Hsp60 · Hsp10 · Apoptosis · Mitochondria
Interleukin‑1 Genotype in Periodontitis
Aniela Brodzikowska1 · Renata Górska2 · Jan Kowalski2
Received: 23 July 2018 / Accepted: 10 July 2019 / Published online: 19 July 2019
© The Author(s) 2019
Abstract
This paper presents the current knowledge concerning the role of polymorphisms of IL1A and IL1B genes in periodontitis.
Attention has been paid to the role of IL-1 in the pathogenesis of the disease, and to the significance of a genetic test, investi-
gating the presence of composite two polymorphisms of IL-1 gene, as a risk factor for severe periodontitis. The significance
of this test for prevention of periodontitis and its therapy has been discussed. IL-1 polymorphisms have been presented and
described according to the reference single nucleotide polymorphism (SNP) identification number (rsID), established to
eradicate the redundancy of reported polymorphisms in the SNP database processed by the National Center for Biotechnology
Information. The prevalence of these genotypes in different populations and ethnic groups and its effect on periodontal health
have been discussed. The presented data show inconsistent results. It seems that at least two polymorphisms, rs1800587 and
rs1143634, are associated with periodontal inflammation. Therefore, they can be regarded as candidate genes involved in
further periodontitis risk assessment. It seems that geographical and ethnical factors can play a great role, as the prevalence
of specific polymorphisms varies greatly depending on the population studied.
Keywords Periodontitis · Genotype · IL-1 · Polymorphisms
Clinical and Immunological Features of 78 Adult Patients with Primary
Selective IgG Subclass Deficiencies
Amrita Khokar1,3 · Sudhir Gupta1,2
Received: 13 January 2019 / Accepted: 23 July 2019 / Published online: 30 July 2019
© L. Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland 2019
Abstract
The purpose of this study is to describe both clinical and immunological features in large cohort of adult patients with IgG
subclass deficiency, and response to immunoglobulin therapy. This is a retrospective study of data obtained from electronic
medical records and paper charts of 78 patients with IgG subclass deficiency seen and followed at our immunology clinics
from 2010 to 2016. Both isolated selective IgG subclass deficiency as well as combined (two) subclass deficiencies were
observed. IgG3 subclass deficiency, isolated and in combination with other IgG subclass deficiency, is the most frequent of
IgG subclass deficiency. A majority of patients presented with upper and lower respiratory tract infections, especially chronic
sinusitis. Both allergic and autoimmune manifestations are common; however, there is no subclass preference. The propor-
tions and absolute numbers of CD3+ T cells, CD4+ T and CD8+ T cells, CD19+ B cells, and CD3−CD16+CD56+ NK cells
were normal in the majority of patients in all IgG subclass deficiencies. Total serum IgG levels did not correlate with IgG
subclass levels across all IgG subclass deficiencies. Anti-pneumococcal polysaccharide antibody responses were impaired
in 56% of patients. IgG3 subclass deficiency is the most common IgG subclass deficiency, and anti-polysaccharide antibody
responses are distributed among IgG subclasses with modest preference in IgG2 subclass. The majority of patients treated
with immunoglobulin responded by reduction in frequency of infections and requirement of antibiotics.
Keywords IgG subclass deficiency · Autoimmunity · Allergic asthma · Specific antibodies · Immunoglobulin therapy
Correction to: Significance and Role of Pattern Recognition Receptors
in Malignancy
Jan Żeromski1 · Mariusz Kaczmarek1 · Maciej Boruczkowski1 · Agata Kierepa2 · Arleta Kowala‑Piaskowska2 ·
Iwona Mozer‑Lisewska2
Published online: 31 August 2019
© The Author(s) 2019
Correction to:
Archivum Immunologiae et Therapiae Experimentalis
(2019) 67:133–141
https ://doi.org/10.1007/s0000 5-019-00540 -x
The authors would like to correct the following error:
In page 139 in Acknowledgements is:
“This work was partly supported by the National Science
Center (NCN) under OPUS Grant 2016/23/B/NZ6/013497
(Awarded to prof. IM-L).”
Should be:
“This work was partly supported by the National Science
Center (NCN) under OPUS Grant 2016/23/B/NZ6/01497
(Awarded to prof. IM-L).”
90th Birthday of Prof. Czesław Radzikowski
Piotr Kuśnierczyk1
Received: 13 August 2019 / Accepted: 20 August 2019 / Published online: 30 August 2019
© L. Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland 2019
Professor Włodzimierz Ptak (1928–2019)
The Member of AITE Advisory Board 1992–1997, 2006–2016
Janusz Marcinkiewicz1
Peripheral Blood B and T Cell Profiles in Children with Active Juvenile
Idiopathic Arthritis
Asmaa M. Zahran1 · Alameldin M. Abdallah2 · Khaled Saad2 · Naglaa S. Osman2 · Mervat A. M. Youssef2 ·
Yasser Farouk Abdel‑Raheem2 · Khalid I. Elsayh2 · Amir M. Abo Elgheet2 · Sanaa F. Darwish3 · Mohamd A. Alblihed4 ·
Amira Elhoufey5,6
Received: 5 July 2019 / Accepted: 9 September 2019 / Published online: 18 September 2019
© L. Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland 2019
Abstract
Juvenile idiopathic arthritis (JIA) is one of the most common autoimmune diseases in children. Our study aimed to evaluate
the peripheral blood B and T lymphocyte subpopulations in children with JIA. This case–control study included 20 children
with JIA as well as 20 healthy children with matching age and sex as a control group. All patients included in the study were
in activity as determined by visual analog scale. In addition to complete clinical evaluation, basic investigations, peripheral
blood B and T lymphocyte subpopulations were done to all participants by flow cytometry. JIA patients displayed a signifi-
cant decrease in IgM memory B lymphocytes, switched memory B lymphocytes, and total memory B lymphocytes when
compared to the healthy controls. The percentages of naïve B lymphocytes were significantly increased in JIA patients than
in controls. Total T lymphocytes, CD8+CD28null cells, and CD4+CD28null cells were significantly increased in JIA patients
as compared to controls. In conclusion; JIA patients have an alteration in both B and T lymphocytes with the predisposition
of memory cells which may have a role in sustaining the JIA disease activity.
Keywords Juvenile idiopathic arthritis · B lymphocytes · T lymphocytes · Children
Gut Microbiota in Neurological Disorders
Marta Grochowska1 · Tomasz Laskus2 · Marek Radkowski1
Received: 12 February 2019 / Accepted: 12 September 2019 / Published online: 1 October 2019
© The Author(s) 2019
Abstract
The incidence of neurological disorders such as multiple sclerosis (MS), Alzheimer’s disease (AD) and Parkinson’s disease
(PD) is increasing throughout the world, but their pathogenesis remains unclear and successful treatment remains elusive.
Bidirectional communications between the central nervous system and gut microbiota may play some role in the pathogenesis
of the above disorders. Up to a thousand bacterial species reside in human intestine; they colonize the gut shortly after birth
and remain for life. Numerous studies point to the role of microbiota composition in the development, course and treatment
of MS, AD and PD.
Keywords Gut · Microbiota · Neurological disorders
Retinoids as an Immunity‑modulator in Dermatology Disorders
Wangqing Chen1,2 · Shuang Zhao2 · Wu Zhu2 · Lisha Wu2,3 · Xiang Chen1,2
Received: 31 January 2019 / Accepted: 13 September 2019 / Published online: 24 September 2019
© L. Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland 2019
Abstract
The skin is the largest epithelial surface protecting the body from invading microbes. Vitamin A plays vital roles in the
host defence of the skin, including promoting epithelial cell integrity, proliferation, and differentiation and even mediat-
ing immune responses. Furthermore, vitamin A derivatives, retinoid drugs, are widely used to treat skin diseases, such as
acne and psoriasis. However, the immunoregulatory mechanisms of retinoids in dermatology have not been systematically
described. In this paper, we discuss the immunological functions of retinoids during disease treatment, especially in skin
disorders caused by exogenous infections.
Keywords Vitamin A · Retinoids · Immunity · Dermatology diseases · Infectious
Modulatory Effect of the Euro‑Lupus Low‑Dose Intravenous
Cyclophosphamide Regimen on Circulating Immune Cells in Systemic
Lupus Erythematosus
Gabriela Gabcova1 · Pavel Horak2 · Zuzana Mikulkova1 · Martina Skacelova2 · Sarka Zehnalova3 ·
Andrea Smrzova2 · Anna Petrackova1 · Frantisek Mrazek1 · Eva Kriegova1
Received: 30 April 2019 / Accepted: 28 September 2019 / Published online: 16 October 2019
© L. Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland 2019
Abstract
A Euro-Lupus regimen of low-dose intravenous cyclophosphamide (CFA) is commonly used to treat severe organ mani-
festations of systemic lupus erythematosus (SLE), particularly lupus nephritis (LN). There are no data on the distributions
and dynamics of immune cell populations in patients with various treatment outcomes. The circulating immune cells of
11 female SLE patients were assessed before and after Euro-Lupus regimen (cumulative dose of 3000 mg CFA) by flow
cytometry together with those of 16 healthy women. A subanalysis was performed in LN patients who achieved complete
remission (CR; n = 3), partial remission (PR; n = 4), and no response (NR; n = 2). In SLE, the Euro-Lupus regimen decreased
the percentage and absolute count of B cells; increased the percentage of CD8+ T cells, T regulatory cells, neutrophils,
and monocyte subsets; and activated T and NK cells compared to healthy controls (P < 0.050). Patients with LN achieving
CR had significantly lower proportions of CD27+ B memory cells compared to poor responders (PR/NR, P = 0.035). The
post-treatment percentages and absolute numbers of B cells, T cells, NK cells, monocytes, and neutrophils showed high
inter-individual variability with no association with treatment outcome. Our pilot study revealed the dynamics of changes
in immune cell populations in SLE patients during a Euro-Lupus regimen, mainly the lowering of B cells. In LN patients
who achieved CR, a lower proportion of CD27+ B memory cells was evident compared to poor responders (PR/NR). Further
studies on usefulness of monitoring immune cells for treatment response prediction on larger cohorts are needed.
Keywords SLE · Cyclophosphamide · Immunophenotyping · Flow cytometry · Treatment outcome · Lupus nephritis
Type III Interferons (Lambda Interferons) in Rheumatic Autoimmune
Diseases
Tania Mora‑Arias1 · Luis M. Amezcua‑Guerra1
Received: 30 April 2019 / Accepted: 10 December 2019 / Published online: 9 January 2020
© L. Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland 2020
Abstract
The last 2 decades have witnessed the discovery and characterization of a new family of cytokines with immunological
characteristics similar to those described for type I interferons, type III or lambda interferons. Unraveling the molecular
mechanisms underlying each type of interferon has allowed us to understand how some autoimmune diseases can be con-
sidered as interferonopathies. Under normal conditions, type III interferons play a key role in the defense against viruses by
modulating the functioning of several types of innate and adaptive immune cells. These effects include upregulation of major
histocompatibility complex molecules by myeloid dendritic cells, increased functioning of pattern recognition receptors by
plasmacytoid dendritic cells, decreased activity of regulatory T cells, enhanced production of antibodies by plasmatic cells
and increased expression of chemokines and adhesion molecules by leukocytes and endothelial cells. Notably, all these
mechanisms have been described to boost autoimmunity, and type III interferons pathway activation has been related to the
pathogenesis of autoimmune conditions such as systemic lupus erythematosus, systemic sclerosis and Sjögren’s syndrome.
This review provides an overview of the current evidence on the contribution of type III interferons in the pathogenesis of
rheumatic autoimmune diseases in humans.
Keywords Interferons · Autoimmunity · Inflammation · Jak/STAT pathway · Systemic lupus erythematosus
HER2‑Positive Breast Cancer Immunotherapy: A Focus on Vaccine
Development
Atefeh Arab1 · Rezvan Yazdian‑Robati2 · Javad Behravan3,4,5
Received: 27 June 2019 / Accepted: 16 December 2019 / Published online: 9 January 2020
© L. Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland 2020
Abstract
Clinical progress in the field of HER2-positive breast cancer therapy has been dramatically improved by understanding of
the immune regulatory mechanisms of tumor microenvironment. Passive immunotherapy utilizing recombinant monoclonal
antibodies (mAbs), particularly trastuzumab and pertuzumab has proved to be an effective strategy in HER2-positive breast
cancer treatment. However, resistance to mAb therapy and relapse of disease are still considered important challenges in
clinical practice. There are increasing reports on the induction of cellular and humoral immune responses in HER2-positive
breast cancer patients. More recently, increasing efforts are focused on using HER2-derived peptide vaccines for active
immunotherapy. Here, we discuss the development of various HER2-derived vaccines tested in animal models and human
clinical trials. Different formulations and strategies to improve immunogenicity of the antigens in animal studies are also
discussed. Furthermore, other immunotherapeutic approaches to HER2 breast cancer including, CTLA-4 inhibitors, immune
checkpoint inhibitors, anti PD-1/PD-L1 antibodies are presented.
Keywords Breast cancer · HER2 · Immunotherapy · Vaccine