Laboratory of Clinical Immunology

  • Transplantation immunology with the study of immune dysregulation as an element of post-transplantation risk.
  • Determination of the immune potential (examination of the TCR beta subset at the NGS level in the context of the overall efficiency of the immune system), examination of lymphocyte subpopulations and antibody response in the course of infection with Herpes and SARS-CoV2 viruses.
  • Identification, functional tests and clinical use of mesenchymal and endothelial stem cells of bone marrow origin.
  • Immunogenetics with particular emphasis on HLA specificity and polymorphism of genes encoding cytokines, chemokines and their receptors.
  • Genetics of blood cancers with particular interest in the profile of genetic disorders
  • Regenerative medicine – research concerning good response to the regeneration of peripheral circulation and joints to the phenotypic profile of bone marrow cells used during surgery in humans.

Kontakt

Head

Head: prof. dr hab. n.med Andrzej Lange, FRCP (https://orcid.org/0000-0003-3544-1853)

Professor Andrzej Lange is the initiator of the Lower Silesian Cell Transplant Center and a pioneering cell propagation center. The Laboratory is responsible for creation of the bone marrow transplant center (1,300 procedures) and the National Bone Marrow Donor Bank (Polish and EBMT, EFI, NMDP, WMDA accreditations). The laboratory uses variety of immunogenetics techniques and have made significant impact on the discovery of polymorphic features of genes encoding cytokines and chemokines important in transplantation and Covid-19. In these areas, in the event of inflammatory overload, a sequence of events leading to immune dysregulation has been documented.

An innovative research on TCRbeta initiated 20 years ago was performed, and now, thanks to next-generation sequencing, the diversity of TCRbeta families in the state of disease has been described. This has great importance, specifically in the era of Covid-19. Regenerative procedures have been performed for 17 years (reversal of circulation in ischemic limbs and avascular bone necrosis, joint regeneration). In addition, phenotypic features of stem cells that are related to biological differentiation pathways have been discovered. Clinically effective modifications of transplant material for pioneering bone marrow transplantation procedures in infants with immunodeficiency were developed and performed.

International activities of the laboratory include 12 global conferences, publishing many books reflecting the Laboratory’s work, and co-editing journals. 160 publications have been published and achieved over 2,100 citations.

Research team
Most important scientific achievements
Research methods
  • Molecular biology: PCR, Rela-Time PCR, SSO, SBT, gene expression testing, genotyping using Real-Time PCR, RLFP etc., expression microarrays and CGH, Next Generation Sequencing (NGS).
  • Flow cytometry – examination of subpopulations of blood and bone marrow cells.
  • MSC cultures.
Main research equipment
  • Real-Time PCR cyclers: Lightcycler II, Roche, Opticon Monitor, MJ research
  • Nucleic acid isolation equipment: Maxwell 15, Promega
  • Sanger sequencing apparatus: Genetic analyzer 3500 (Life Technologies)
  • Bioanalyzer (Agilent)
  • Nimblegene Micrometer Apparatus (Roche)
  • Nanodrop (Thermofisher)
  • MagnaLyser (Roche)
  • Laminar Chamber (Camfil)
  • ThermoForma Incubator (Thermofisher)
  • Eppendorf preparative centrifuges and microcentrifuges
  • Bio-Rad thermal cyclers
Main research projects (recent 10 years)
  • Innovative development and implementation of a regenerative large joints procedure in human clinics (STAWREG). RPDS.01.02.01-02-0177/17 scheme 1.2.A Support for enterprises wanting to start or expand R&D activities, project under the Regional Operational Program of the Lower Silesian Voivodeship 2014-2020. Implementation period: 23/01/2018-26/10/2020, head: Professor Andrzej Lange, Ph.D. n. med. Task 5. Development of a method and application for the functional assessment of cell populations of bone marrow origin for bone-forming, cartilage-forming and fat-forming potential.
  • Development of a method of administering (1) hematopoietic cells together with mesenchymal stromal cells as a protective element and (2) killing leukemia cells to bones, NCBiR research project no. INNOMED/I/1/NCBR/2014. Implementation period: 01/01/2014-30/06/2017 Task 1. DLI cell line: Determination – profiling of lymphocytes isolated (Cobe Spectra 2930) from peripheral blood after and without G-CSF stimulation for the purpose of infusion of donor lymphocytes. Task 2. MSC cell line: Enrichment of material with cells isolated from bone marrow aspirate samples by negative selection, using RosetteSep MSC Enrichement Coctail (Stem Cells Technology, Canada) containing glycophorin A, CD3, CD14, CD19, CD6. Task 3. DLI cell line: Characterization of cells at various stages of isolation and enrichment (tasks 1 and 2) to determine the transcript profile of activated T lymphocytes, characterization of stem cells – RT-PCR platform.
  • Study on the differentiation of the immune response (Th1 vs. Th17) and the activity of regulatory cells (nTreg) in patients after hematopoietic cell transplantation, NCN research project no. N-N402-43-0039. Implementation period: 07/2010-30/06/2013, head: Professor Andrzej Lange, Ph.D. n. med. FRCP.
  • Implementation and national harmonization of immunogenetic tests supporting the final decision on the selection of a recipient-alternative donor pair for allogeneic hematopoietic cell transplantation, NCBiR research project no. R13 0082 06. Implementation period: 09/2009-31/08/2012, head: Professor Andrzej Lange, Ph.D. n. med. FRCP.
Selected publications
  • Jaskuła E., Lange A.: Ability of the immune system to fight viruses highlighted by cytometry and T-cell receptor clonotype assessment: lessons taken before the coronavirus disease 2019 pandemic outbreak. Pol Arch Intern Med, 2020, 130(7-8): 662-667 (https://doi.org/10.20452/pamw.15388).
  • Lange A., Wodzińska-Maszko I., Pakos H., Sobczyńska-Konefał A., Lange J., Mordak-Domagała M., Bocheńska J., Jaskuła E.: Intra-bone donor lymphocyte infusion at relapse: clinical outcome is associated with presence of CD8+ cells in the marrow. Bone Marrow Transplant, 2020, 55(5): 974-978 (https://doi.org/10.1038/s41409-019-0632-z).
  • Nowak J., Nestorowicz K., Graczyk-Pol E., Mika-Witkowska R., Rogatko-Koros M., Jaskula E., Koscinska K., Madej S., Tomaszewska A., Nasilowska-Adamska B., Szczepinski A., Halaburda K., Dybko J., Kuliczkowski K., Czerw T., Giebel S., Holowiecki J., Baranska M., Pieczonka A., Wachowiak J., Czyz A., Gil L., Lojko-Dankowska A., Komarnicki M., Bieniaszewska M., Kucharska A., Hellmann A., Gronkowska A., Jedrzejczak W.W., Markiewicz M., Koclega A., Kyrcz-Krzemien S., Mielcarek M., Kalwak K., Styczynski J., Wysocki M., Drabko K., Wojcik B., Kowalczyk J., Gozdzik J., Pawliczak D., Gwozdowicz S., Dziopa J., Szlendak U., Witkowska A., Zubala M., Gawron , Warzocha K., Lange A.: HLA-inferred extended haplotype disparity level is more relevant than the level of HLA mismatch alone for the patients survival and GvHD in T cell-replate hematopoietic stem cell transplantation from unrelated donor. Hum Immunol, 2018, 79(6): 403-412 (https://doi.org/10.1016/j.humimm.2018.03.011).
  • Lange A., Jaskula E., Lange J., Dworacki G., Nowak D., Simiczyjew A., Mordak-Domagala M., Sedzimirska M.: The sorafenib anti-relapse effect after alloHSCT is associated with heightened alloreactivity and accumulation of CD8+PD-1+ (CD279+) lymphocytes in marrow. PLoS One, 2018, 13(1): e0190525 (https://doi.org/10.1371/journal.pone.0190525) (Erratum in: PLoS One, 2018, 13(12): e0209108).
  • Spólnicka M., Piekarska R.Z., Jaskuła E., Basak G.W., Jacewicz R., Pięta A., Makowska Ż., Jedrzejczyk M., Wierzbowska A., Pluta A., Robak T., Berent J., Branicki W., Jędrzejczak W., Lange A., Płoski R.: Donor age and C1orf132/MIR29B2C determine age-related methylation signature of blood after allogeneic hematopoietic stem celltransplantation. Clin Epigenetics, 2016, 8(1):93 (https://doi.org/10.1186/s13148-016-0257-7) (Erratum in: Clin Epigenetics, 2016 Nov 18, 8: 121).
  • Jaskula E., Dlubek D., Tarnowska A., Lange J., Mordak-Domagala M., Suchnicki K., Sedzimirska M., Borowik A., Mizia S., Lange A.: Anti-CMV-IgG positivity of donors is beneficial for alloHSCT recipients with respect to the better short-term immunological recovery and high level of CD4+CD25high lymphocytes. Viruses, 2015, 7(3): 1391-408 (https://doi.org/10.3390/v7031391).
  • Bogunia-Kubik K., Mizia S., Polak M., Gronkowska A., Nowak J., Kyrcz-Krzemień S., Markiewicz M., Dzierżak-Mietła M., Koclęga A., Sędzimirska M., Suchnicki K., Duda D., Lange J., Mordak-Domagała M., Kościńska K., Jędrzejczak W.W., Kaczmarek B., Hellmann A., Kucharska A., Kowalczyk J., Drabko K., Warzocha K., Hałaburda K., Tomaszewska A., Mika-Witkowska R., Witkowska A., Goździk J., Mordel A., Wysoczańska B., Jaskula E., Lange A.: POLISH DONOR–RECIPIENT STUDY GROUP. Beneficial effect of the CXCL12-3’A, variant for patients undergoing hematopoietic stem cell transplantation from unrelated donors. Cytokine, 2015, 76(2): 182-186 (https://doi.org/10.1016/j.cyto.2015.05.001).
  • Bogunia-Kubik K., Mizia S., Gronkowska A., Nowak J., Kyrcz-Krzemień S., Markiewicz M., Dzierżak-Mietła M., Koclęga A., Sędzimirska M., Suchnicki K., Duda D., Lange J., Mordak-Domagała M., Kościńska K., Węzik S., Jędrzejczak W.W., Kaczmarek B., Hellmann A., Kucharska A., Kowalczyk J., Drabko K., Warzocha K., Mika-Witkowska R., Goździk J., Lange A.: CCR5 gene polymorphism affects the risk of GvHD after haematopoietic stem cell transplantation from an unrelated donor. Br J Haematol, 2015, 171(2): 285-288 (https://doi.org/10.1111/bjh.13387).
  • Jaskula E., Lange A., Kyrcz-Krzemien S., Markiewicz M., Dzierzak-Mietla M., Jedrzejczak W.W., Czajka P., Mordak-Domagala M., Lange J., Gronkowska A., Nowak J., Warzocha K., Hellmann A., Kowalczyk J., Drabko K., Gozdzik J., Mizia S.: Polish Donor-Recipient Matching Group. NOD2/CARD15 single nucleotide polymorphism 13 (3020insC) is associated with risk of sepsis and single nucleotide polymorphism 8 (2104C>T) with herpes viruses reactivation in patients after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant, 2014, 20(3): 409-14 (https://doi.org/10.1016/j.bbmt.2013.12.558).
  • Lange A., Dlubek D., Zdziarski R., Chodorowska A., Mordak-Domagala M., Klimczak , Lange J., Jaskula E.: Donor lymphocyte infusions to leukemic bone lesions are therapeutically effective in a Ph+ ALL patient with post-HSCT relapse. J Immunotoxicol, 2014, 11(4): 347-52 (https://doi.org/10.3109/1547691X.2014.893042).
  • Jaskula E., Lange A., Dlubek D., Kyrcz-Krzemień S., Markiewicz M., Dzierzak-Mietla M., Jedrzejczak W.W., Gronkowska A., Nowak J., Warzocha K., Hellmann A., Kowalczyk J., Drabko K., Goździk J., Mizia S.: Polish Donor‐Recipient Matching Group. IL-10 promoter polymorphisms influence susceptibility to aGvHD and are associated with proportions of CD4+FoxP3+ lymphocytes in blood after hematopoietic stem cell transplantation. Tissue Antigens, 2013, 82(6): 387-96 (https://doi.org/10.1111/tan.12255).
  • Jaskula E., Dlubek D., Sedzimirska M., Duda D., Tarnowska A., Lange A.: Reactivations of cytomegalovirus, human herpes virus 6, and Epstein-Barr virus differ with respect to risk factors and clinical outcome after hematopoietic stem cell transplantation. Transplant Proc, 2010, 42(8): 3273-6 (https://doi.org/1016/j.transproceed.2010.07.027).