HLA-B27/microbial mimicry: an in vivo analysis

Area of Science:

• Immunology
• Rheumatology
• Molecular Biology

Background:

• The human leukocyte antigen (HLA) B27 is strongly associated with spondyloarthritic diseases.
• A proposed mechanism involves molecular mimicry, where bacterial antigens resemble HLA-B27, triggering an autoimmune response.
• In vitro studies suggested cross-reactivity between HLA-B27 and Gram-negative bacteria.

Purpose of the Study:

• To investigate the in vivo molecular mimicry hypothesis between HLA-B27 and arthritogenic bacteria.
• To determine if antibodies generated against bacteria cross-react with HLA-B27 in a living system.

Main Methods:

• Transfected mouse L cells expressing HLA-B27 or HLA-A3 were used as antigen sources.
• Western blot analysis of denatured antigen, FACS analysis of native antigen, and immunoprecipitation were employed.
• Rabbit and human patient sera containing antibodies against bacteria were tested for cross-reactivity.

Main Results:

• No cross-reacting antibodies to HLA-B27 were detected in vivo using any of the applied methods.
• Antibodies generated in vivo against arthritogenic bacteria did not show cross-reactivity with HLA-B27.
• The humoral immune response did not support molecular mimicry as a cause of reactive arthritis.

Conclusions:

• Molecular mimicry, as defined by the humoral immune response, is unlikely to explain the role of HLA-B27 in reactive arthritis pathogenesis.
• The findings suggest that other mechanisms may be involved in the development of HLA-B27-associated spondyloarthritic diseases.
• Further research is needed to elucidate the precise role of HLA-B27 in these conditions.