IgVH-genes analysis from psoriatic arthritis shows involvement of antigen-activated synovial B-lymphocytes

Abstract

The pathogenesis of psoriatic arthritis (PA), which occurs in 5-7% of patients with psoriasis vulgaris, is enigmatic. There are no molecular data about synovial B-cells of chronic synovitis of PA. In order to understand the B-cell response in PA, we analysed IgVH genes and specified replacement to silent mutation (R/S) ratios of the complementarity determining regions (CDR) and framework regions (FR) as well as VH families. To prove the existence of a common pattern we additionally analysed the IgVH genes at the amino-acid level. From 5 PA patients we took cryo-tissue sections with somatically mutated IgVH genes (sum R/sum S in the CDRs: 2.5-6.8), 62 of which were analysed. In one patient two cases of clonally related IgVH genes were observed. Identical amino-acid replacements in IgVH1 and IgVH4 were found at the same mutational "cold spot". These data indicate that antigen-activated B-cells participate in the formation of chronic synovitis of PA. Since, neither histopathologically nor immunohistochemically, no germinal centres could be detected, the clonally related IgVH genes may be interpreted as residues of a germinal centre reaction that occurred before synovectomy. The existence of identical amino-acid replacement mutations in IgVH1 and IgVH4 genes suggests that a limited number of antigens are common to all PA patients analysed. The recombinant expression of the IgVH could help to define B-cell specificities underlying the pathogenesis of chronic synovitis and dermatitis of PA.