We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Effects of type II collagen epitope carbamylation and citrullination in human leucocyte antigen (HLA)-DR4<sup>+</sup> monozygotic twins discordant for rheumatoid arthritis.
- Authors
De Santis, M.; Ceribelli, A.; Cavaciocchi, F.; Generali, E.; Massarotti, M.; Isailovic, N.; Crotti, C.; Scherer, H. U.; Montecucco, C.; Selmi, C.
- Abstract
The aim of this study is to investigate the effect of the native, citrullinated or carbamylated type II human collagen T cell- and B cell-epitopes on the adaptive immune response in rheumatoid arthritis (RA). Peripheral blood T and B cells obtained from a human leucocyte D4-related (antigen DR4− HLA-DR4)+ woman with early RA, her healthy monozygotic twin and an unrelated HLA-DR3+ woman with early RA were analysed for activation (CD154/CD69), apoptosis (annexin/7-aminoactinomycin), cytokine production [interferon (IFN)γ/interleukin (IL)−17/IL-4/IL-10/IL-6] and functional phenotype (CD45Ra/CCR7) after stimulation with the collagen native T cell epitope (T261-273), the K264 carbamylated T cell epitope (carT261-273), the native B cell epitope (B359-369) or the R360 citrullinated B cell epitope (citB359-369), and the combinations of these. The T cell memory compartment was activated by T cell epitopes in both discordant DR4+ twins, but not in the DR3+ RA. The collagen-specific activation of CD4+ T cells was induced with both the native and carbamylated T cell epitopes only in the RA twin. Both T cell epitopes also induced IL-17 production in the RA twin, but a greater IL-4 and IL-10 response in the healthy twin. The citrullinated B cell epitope, particularly when combined with the carbamylated T cell epitope, induced B cell activation and an increased IL-6/IL-10 ratio in the RA twin compared to a greater IL-10 production in the healthy twin. Our data suggest that circulating collagen-specific T and B cells are found in HLA-DR4+ subjects, but only RA activated cells express co-stimulatory molecules and produce proinflammatory cytokines. Carbamylation and citrullination further modulate the activation and cytokine polarization of T and B cells.
- Subjects
RHEUMATOID arthritis -- Immunological aspects; COLLAGEN; EPITOPES; CITRULLINE; HLA histocompatibility antigens; IMMUNE response
- Publication
Clinical & Experimental Immunology, 2016, Vol 185, Issue 3, p309
- ISSN
0009-9104
- Publication type
Article
- DOI
10.1111/cei.12825