Significant differences in B-cell subpopulations characterize patients with chronic graft-versus-host disease-associated dysgammaglobulinemia.
Manifestations of chronic graft-versus-host disease (cGVHD) can resemble those seen in immunodeficiency states and autoimmune disorders. Reports by us and others suggest an involvement of B cells in the pathogenesis of cGVHD. We investigated B-lymphocyte subpopulations in cGVHD cohorts defined by serum immunoglobulin G (IgG) levels to characterize novel biomarkers for impairment of humoral immunity after allogeneic hematopoietic stem cell transplantation. Seventy-six patients were enrolled a median of 46 months after hematopoietic stem cell transplantation. The hypogammaglobulinemia group had significantly diminished CD19(+) B cells (165 vs 454 vs 417 × 10⁶L) with elevated CD19(+)CD21(low) immature (16.5%, 7.7%, and 9.1%) and CD19(+)CD21(int-high)CD38(high)IgM(high) transitional (10.5% vs 4.2% vs 6.3%) B-cell proportions compared with the normogammaglobulinemia and hypergammaglobulinemia groups. CD19(+)CD10(-)CD27(-)CD21(high) naive B cells were highly elevated in all patients with cGVHD. CD19(+)CD27(+)IgD(+) non-class-switched (4 vs 12 vs 11 × 10⁶/L) and class-switched (7 vs 35 vs 42 × 10⁶/L) memory B cells were significantly lower in the hypogammaglobulinemia group compared with the others. Besides significantly higher B-cell activation factor/B-cell ratios, significantly more cGVHD patients with hypergammaglobulinemia had autoantibodies compared with the hypogammaglobulinemia subgroup (68% vs 24%, P = .024). In conclusion, B-cell subpopulations can serve as novel cellular biomarkers for immunodeficiency and autoimmunity indicating different pathogenetic mechanisms of cGVHD and encouraging future prospective longitudinal studies.
Department of Internal Medicine I, Bone Marrow Transplantation, Medical University of Vienna, Vienna, Austria.
Zoya
Z
Kuzmina
Hildegard T
HT
Greinix
Roman
R
Weigl
Ulrike
U
Körmöczi
Arno
A
Rottal
Sophie
S
Frantal
Sandra
S
Eder
Winfried F
WF
Pickl
D000328:Adult; D001323:Autoantibodies / Q000097:blood; D053264:B-Cell Activating Factor / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D002908:Chronic Disease; D015331:Cohort Studies; D017074:Common Variable Immunodeficiency / Q000209:etiology / Q000276:immunology; D004406:Dysgammaglobulinemia / Q000209:etiology* / Q000276:immunology*; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology* / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D006942:Hypergammaglobulinemia / Q000209:etiology / Q000276:immunology; D056724:Immunity, Humoral; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D008875:Middle Aged; D014184:Transplantation, Homologous; D055815:Young Adult
D001323:Autoantibodies; D053264:B-Cell Activating Factor; D007074:Immunoglobulin G; C505719:TNFSF13B protein, human