Comprehensive analysis of serum immune complexes identifies chronic graft-versus-host disease-associated antigenic...

Chronic graft-versus-host disease (cGVHD) is an alloimmune disease characterized by inflammation, immune dysregulation, and pathogenic fibrosis after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Donor-derived B cells have a significant role of cGVHD development; however, the proteins targeted by B cell-mediated cGVHD remain unclear. To identify cGVHD-associated antigens, we investigated immune complexes (ICs) in the serum of patients who underwent allo-HSCT. Of the 26 patients examined, 17 developed cGVHD, and the 1-year cumulative incidence of cGVHD was 57.7%. A comprehensive analysis of ICs identified 89 distinct IC-associated antigen candidates, including significantly enriched clusters associated with "regulation of secretion by cell", "regulation of protein kinase activity", "positive regulation of organelle organization", and "positive regulation of synaptic transmission". Regarding overlap between the tissue specificity of proteins and cGVHD-affected organs, ten proteins were identified as organ-specific antigen candidates. In summary, the immune complexome analysis identified antigen candidates in patients with cGVHD, suggesting that the heterogeneity of target proteins might lead to, at least in a part, diverse clinical manifestations of cGVHD. The results of this study provide important insights into immune dysregulation in cGVHD.