Presence of aberrant VH6 domains in anti-interferon-γ autoantibodies in multiple sclerosis

摘要

BACKGROUND: Anti-cytokine autoantibodies (auto-Abs) are ubiquitous both in patients suffering from infectious, inflammatory and autoimmune diseases and in healthy individuals. Particularly anti-IFN-γ auto-Abs are shown to be elevated in blood of multiple sclerosis (MS) patients. OBJECTIVE: The aim of present study was to investigate whether repertoires of anti-IFN-γ auto-Abs differ in MS patients and healthy donors. METHODS: Using phage display technique we have compared repertoires of the genes encoding anti-IFN-γ single-chain variable fragments selected from MS and na?ve phage display libraries. RESULTS: The panel of anti-IFN-γ auto-Abs selected from MS library includes (i) 'fetal' auto-Abs, encoded by the VH6-1 gene segment and the combination proximal D segments with distal JH segments; (ii) na?ve auto-Abs; (iii) affinity maturated antibodies; and (iv) abnormal single-domain antibodies. Meanwhile, the panel of anti-IFN-γ auto-Abs selected from na?ve library mainly contains the na?ve antibodies. Moreover, the overall antibody repertoire of MS library is skewed compared to the overall repertoire of na?ve library and also contained the antibodies carrying a 'fetal' VH6 domain and the ratio of κ and λ chains was reversed. CONCLUSIONS: These results suggest existence of a special mechanism or trigger that provides for reconstitution of the immune system in MS.