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ctt-journal > Kuzmina Z.2 et al. (Abstract)

Kuzmina Z.2 et al. (Abstract)

Cellular Therapy and Transplantation (CTT), Vol. 3, No. 9
doi: 10.3205/ctt-2010-No9-abstract60
© The Authors. This abstract is provided under the following license: Creative Commons Attribution 3.0 Unported

Abstract accepted for "4th Raisa Gorbacheva Memorial Meeting on Hematopoietic Stem Cell Transplantation",
Saint Petersburg, Russia, September 18–20, 2010

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Immature autoreactive B cells may predict treatment response in chronic graft-versus-host disease (cGVHD)

Zoya Kuzmina1, Roman Weigl1, Ulrike Körmöczi3, Arno Rottal3, Christoph Zielinski1, Robert Knobler2, Winfried Pickl3, Hildegard Greinix2

1Internal Medicine I, Bone Marrow Transplantation, Medical University of Vienna, Vienna, Austria; 2Dermatology, Medical University of Vienna, Vienna, Austria; 3Institute of Immunology, Medical University of Vienna, Vienna, Austria

Correspondence: Zoya Kuzmina, Medical University of Vienna, Internal Medicine I, Bone Marrow Transplantation Department, Waehringer Guertel 18-20, 1090, Vienna, Austria, E-mail: zoya.kuzmina@spam is badmeduniwien.ac.at

Abstract

cGvHD after allogeneic bone-marrow transplantation is associated with B cell disturbances/autoreactivity. Indications of cGVHD can mimic autoimmune diseases, and auto-antibodies derived from B cells have been found. Therapy of cGvHD involves immunosuppressive (IS) agents with differing effects. Identification of specific biomarkers could thus be used to address these problems.

Patients and methods: We investigated B cell subsets in peripheral blood (PB) of 74 pts. Therapies were cyclosporine A (CSA n=24), tacrolimus (n=13), sirolimus (n=18), and ECP (n=19) for moderate (n=29) or severe (n=45) cGVHD (NIH criteria). Organ involvement included: skin (61%), oral mucosa (68%), eyes (38%), liver (30%), and lungs (31%). PB leukocytes were analyzed after staining for CD19, CD27, CD21, and surface Ig.

Results: Overall, 45 pts (61%) responded to therapy including 83% given CSA, 46% on tacrolimus, 39% on sirolimus, and 63% given ECP, respectively. Prior to IS therapy non-responders had significantly (p=0.03) higher proportions of immature CD19+CD21- B-lymphocytes with a mean of 19.4% compared with a mean of 13.3% in responders. There were significantly higher proportions of immature CD19+CD21- B-cells in non-responders compared to responders to sirolimus (mean of 23% vs. 9.3%, p=0.02), tacrolimus (mean of 17.9% vs. 8.6%, p=0.02), or ECP (mean of 22% vs. 13.7%, p=0.04). After 6 months of immunosuppressives all responding patients had a significant (p=0.01) decrease in immature CD19+CD21- B-lymphocytes (13.3% vs. 8.2%).

In conclusion, relative amounts of immature CD19+CD21- B-lymphocytes serially assessed prior to start of cGVHD therapy may predict the response to systemic therapy. Increased proportions of CD21- B-lymphocytes could be part of the autoimmune pathogenesis resulting in autoreactive B-cells in cGVHD. This novel cellular biomarker should be investigated in larger cohorts of patients.

Keywords: hematopoietic stem cell transplantation, chronic graft-versus-host disease, B-cells, biomarker, immunosuppressive therapy

 

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