HLA-B27M1M2 and high immune responsiveness to Shigella flexneri in post-dysenteric arthritis

Abstract The heterogeneous HLA-B27 antigen is closely associated with post-infectious or reactive arthritis (ReA) and is comprised of two serologically defined variants: B27M1 + M2 + and B27M1 + M2 − . An outbreak of dysentery ( n = 120) caused by a Shigella flexneri 2a strain, which possessed cell envelope antigens with epitopes resembling B27M2, resulted in five B27M1 + M2 + patients with ReA. The remaining seven B27M1 + M2 + , one B27M1 − M2 − and all but three B27-negative patients remained free of joint symptoms; the latter three displayed arthralgia. IgM, IgG and IgA serum titers were statistically raised in all patient groups, but were exceptionally and persistently high in the B27M1 + M2 + patients with ReA, especially IgA, as determined in acute-phase sera and sera sampled 1 year after dysentery. B27M1 + M2 + thus appears to be a marker for a subset of disease, characterized by a high immune response. It is concluded that the B27M2 epitope is not unequivocally disease-related to Shigella ReA, that B27M1 + M2 + is not likely to be the only immune-response-regulating gene involved in this form of ReA and that cross-reactivity between bacterial antigenic epitopes and B27 can only be part of a multifactorial process leading to ReA and in itself not sufficient to produce ReA. The intensity of the immune response appears to be another important factor.