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Regulatory B Cells Deficiency in Sclerotic-Type Cutaneous Chronic Graft-Versus-Host Disease

Track: Poster Abstracts
Saturday, March 1, 2014, 6:45 PM-7:45 PM
Longhorn Hall E (Exhibit Level 1) (Gaylord Texan)
Zoya Kuzmina, MD , Experimental Transplantation and Immunology Branch, National Cancer Institute, NIH, Bethesda, MD
Jeremy J Rose , Experimental Transplantation and Immunology Branch, National institute of Health, National Cancer Institute NCI, Bethesda, MD
Kristin Baird, MD , Pediatric Oncology Branch, National Cancer Institute, NIH, Bethesda, MD
Haley Bharat Naik, MD , Dermatology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD
Edward W Cowen, MD , Dermatology Branch, National Cancer Institute, NIH, Bethesda, MD
Steven Z. Pavletic, MD , Experimental Transplantation and Immunology Branch, National Cancer Institute, Bethesda, MD
Fran Hakim, PhD , Experimental Transplantation and Immunology Branch, NCI, Bethesda, MD
Background: Sclerotic-type chronic graft versus host disease (Scl-cGVHD) is a late manifestation of cGVHD that can lead to significant functional disability and morbidity. Scl-cGVHD is often refractory to treatment and its pathogenesis remains poorly understood. Recent studies on a murine model of Scl-cGVHD have proposed that regulatory B cells (Breg) may play a role in controlling development of early T cell infiltrates and later skin fibrosis skin. Although cGVHD has been associated with the presence of autoantibodies, elevated B cell activation factor, and increases in atypical B cell populations, alterations in Breg populations have not been explored. We therefore examined Breg populations in a cohort of severe Scl-cGVHD patients with sclerotic changes affecting > 50% body surface area (BSA).

Patients and methods: In humans, two B cell populations have been identified as capable of producing IL-10 and having suppressive activity: B10 cells (CD27+CD24+) and B1 cells (CD24+CD38++). CD1dhiCD5+ B cells (B10 pro) were also described as the source of IL10. We assessed the expression of CD1d, CD5, CD24, CD39, CD43, CD27 and CD38 on B cells in peripheral blood of patients enrolled in a cross-sectional natural history study of cGVHD (clinicaltrials.gov #NCT00331968). P values comparing populations were determined using Mann-Whitney nonparametric analyses.

Results: B cells in 25 patients with severe Scl-cGVHD (median affected BSA=65%) were compared to cGVHD patients without cutaneous sclerosis (n=6), and to allogeneic transplant patients without cGVHD (n = 7). Patients were assessed at a median of 4 years after transplant and a median duration of 3 years of cGVHD. The overall frequency of CD19+ B cells was comparable in cGVHD and non-cGVHD patients. B10 B cells (CD27+CD24+) were significantly diminished in Scl-cGVHD when compared to nonScl-cGVHD (4.6 vs. 7.0%, p=.022), as well as to non-cGVHD (4.6 vs. 8.2% p=0.026). B10 pro population (CD1d+CD5+) in Scl-cGVHD were significantly diminished only relative to nonScl-cGVHD (4.5 vs. 7.5%, p=.014). B1 B cells (CD24+CD38++) were not different from the other groups. Finally, we further compared patients with active cGVHD (n=22) and found significantly decreased B10 cells compared to patients with stable disease, (4 vs. 9%, p<0.0001).

Conclusion: A reduced frequency of Breg populations was observed in Scl-cGVHD patients, and this reduction was associated with active cGVHD. Functional analysis is necessary to validate a regulatory role of B1 and B10 B cell subsets in Scl-cGVHD.

Disclosures:
Nothing To Disclose
See more of: Poster Session 2: GVH/GVL
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