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Molecular mimicry between human leukocyte antigen B27 and Klebsiella. Consequences for spondyloarthropathies
P L Schwimmbeck1, M B Oldstone
1Department of Immunology, Research Institute of Scripps Clinic, La Jolla, California.
Abstract:
Ankylosing spondylitis and Reiter's syndrome are the two major spondyloarthropathies highly associated with human leukocyte antigen (HLA) B27. Although the development of spondylitis is unclear, it has been hypothesized that HLA-B27 may predispose to spondyloarthropathies via the phenomenon of molecular mimicry. A computer search for homologies between HLA-B27 and microbes revealed a sequence of six consecutive amino acids (glutamine-threonine-aspartic acid-arginine-glutamic acid-aspartic acid) shared by HLA-B27.1 (residues 72 to 77), and Klebsiella pneumoniae nitrogenase (residues 188 to 193). Antibodies raised against a peptide derived from HLA-B27 containing this six-amino-acid sequence cross-reacted with the peptide derived from Klebsiella that contained these six amino acids, and vice-versa. These antibodies also reacted with articular tissues from HLA-B27-positive patients with ankylosing spondylitis. Sera from 53 percent of Reiter's patients and 27 percent of patients with ankylosing spondylitis showed binding to these same peptides. These results suggest that molecular mimicry may have a role in disease development.
Insights
Molecular mimicry may link human leukocyte antigen B27 (HLA-B27) to spondyloarthropathies. Shared amino acid sequences between HLA-B27 and Klebsiella pneumoniae suggest a potential mechanism for ankylosing spondylitis and Reiter's syndrome development.
Area of Science:
- Immunology
- Molecular Biology
- Rheumatology
Background:
- Ankylosing spondylitis and Reiter's syndrome are major spondyloarthropathies strongly associated with human leukocyte antigen B27 (HLA-B27).
- The exact mechanism by which HLA-B27 contributes to spondyloarthropathy development remains unclear.
- Molecular mimicry, where the immune system mistakenly targets self-antigens due to similarity with foreign antigens, is a hypothesized mechanism.
Purpose of the Study:
- To investigate the potential role of molecular mimicry in the pathogenesis of HLA-B27-associated spondyloarthropathies.
- To identify shared molecular sequences between HLA-B27 and microbial antigens.
Main Methods:
- A computer search was performed to identify sequence homologies between HLA-B27 and microbial proteins.
- Antibodies were raised against a specific peptide sequence from HLA-B27.
- Cross-reactivity assays were conducted using these antibodies against microbial peptides and patient samples.
Main Results:
- A six-amino-acid sequence homology was identified between HLA-B27.1 and Klebsiella pneumoniae nitrogenase.
- Antibodies against the HLA-B27 peptide cross-reacted with the Klebsiella peptide and vice versa.
- These antibodies also reacted with articular tissues from HLA-B27-positive ankylosing spondylitis patients.
- Sera from 53% of Reiter's patients and 27% of ankylosing spondylitis patients showed binding to these peptides.
Conclusions:
- The findings suggest that molecular mimicry, specifically involving a shared sequence between HLA-B27 and Klebsiella pneumoniae, may play a role in the development of ankylosing spondylitis and Reiter's syndrome.
- This molecular mimicry could trigger an autoimmune response against joint tissues in susceptible individuals.