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HLA-B27 and pathogenesis of spondyloarthropathies
Matthew J Turner1, Robert A Colbert
1William S. Rowe Division of Rheumatology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA.
Abstract:
Although the influence of HLA-B27 on the development of spondyloarthropathies is undisputed, its role in pathogenesis remains unclear. New ideas have focused on abnormal characteristics of HLA-B27 resulting from aberrant folding, disulfide bond formation, or both, rather than a predilection for selecting arthritogenic peptides. This reflects, in part, unanswered questions about whether immunologic recognition of HLA-B27 is required for disease. Recent studies suggest that CD4+ T cells, immunomodulatory killer cell Ig receptors, and Ig-like transcript receptors may recognize aberrant forms of HLA-B27. Other reports suggest that HLA-B27 expression can alter cytokine production from monocytes and T cells-effects that appear unrelated to antigen presentation. Novel bioinformatics approaches have led to the identification of HLA-B27-restricted pathogen-derived peptides and may prove useful in determining whether HLA-B27 presents arthritogenic peptides. Elucidating the role of HLA-B27 in the pathogenesis of these conditions will require an integration of information from animal models, genome-wide screens for susceptibility alleles, and translational studies using human samples.
Insights
The human leukocyte antigen B27 (HLA-B27) gene
Area of Science:
- Immunogenetics
- Molecular pathogenesis
- Rheumatology
Background:
- The role of HLA-B27 in spondyloarthropathies is established, but its exact pathogenic mechanism remains elusive.
- Current hypotheses suggest aberrant HLA-B27 folding or disulfide bonding, rather than peptide selection, may drive disease.
- Uncertainty persists regarding the necessity of immune recognition of HLA-B27 for disease development.
Purpose of the Study:
- To explore novel insights into the pathogenesis of HLA-B27-associated spondyloarthropathies.
- To investigate the potential roles of aberrant HLA-B27 forms and altered immune cell functions.
- To assess the utility of bioinformatics in identifying potential arthritogenic peptides.
Main Methods:
- Review of recent studies on HLA-B27 structure and immune cell interactions.
- Analysis of reports on HLA-B27's effects on cytokine production.
- Application of bioinformatics to identify HLA-B27-restricted peptides.
Main Results:
- Emerging evidence indicates recognition of aberrant HLA-B27 forms by CD4+ T cells and other immune receptors.
- HLA-B27 expression influences monocyte and T cell cytokine profiles independently of antigen presentation.
- Bioinformatics approaches have identified HLA-B27-associated pathogen-derived peptides.
Conclusions:
- Pathogenesis may involve aberrant HLA-B27 misfolding and subsequent immune recognition.
- Altered cytokine production by immune cells is a potential disease mechanism.
- Further research integrating animal models, genetic studies, and human samples is crucial for full elucidation.