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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.
Insights
The HLA-B27 antigen variant B27M1+M2+ is linked to reactive arthritis (ReA) following Shigella dysentery. High IgA levels in B27M1+M2+ patients suggest immune response intensity is crucial for ReA development.
Area of Science:
- Immunology
- Rheumatology
- Microbiology
Background:
- The human leukocyte antigen (HLA)-B27 is strongly associated with reactive arthritis (ReA).
- HLA-B27 exists in variants, including B27M1+M2+ and B27M1+M2-.
- Shigella flexneri 2a infections can trigger reactive arthritis.
Purpose of the Study:
- To investigate the role of HLA-B27 variants in reactive arthritis following Shigella dysentery.
- To determine if bacterial epitopes resembling B27M2 are directly causative of ReA.
- To explore the association between immune response intensity and ReA development.
Main Methods:
- Studied an outbreak of Shigella flexneri 2a dysentery (n=120).
- Assessed HLA-B27 antigen variants (B27M1+M2+, B27M1+M2-, B27-negative) in patients with and without ReA.
- Measured serum immunoglobulin (IgM, IgG, IgA) titers in acute and follow-up samples.
Main Results:
- Five B27M1+M2+ patients developed ReA after Shigella infection.
- Elevated and persistent IgA titers were observed in B27M1+M2+ patients with ReA.
- Other HLA-B27 variants and negative individuals generally did not develop ReA, though some experienced arthralgia.
Conclusions:
- The B27M1+M2+ HLA-B27 variant may indicate susceptibility to a specific subset of ReA.
- Bacterial epitope mimicry alone is insufficient to cause Shigella-induced ReA.
- The intensity of the host immune response, particularly IgA, is a critical factor in ReA pathogenesis.