nitrogenase and Arthritis--Reactive

Topics: Amino Acid Sequence; Arthritis, Reactive; Cross Reactions; HLA-B27 Antigen; Humans; Klebsiella Infections; Klebsiella pneumoniae; Molecular Sequence Data; Nitrogenase; Pneumonia; Spondylitis, Ankylosing

Some microorganisms which are pathogenic in humans share amino acid sequences with human proteins (molecular mimicry). It has been suggested that molecular mimicry might be a reason for autoimmunity as a result of immunological cross reactivity. A homologous sequence of six amino acids has been found in both Klebsiella pneumoniae nitrogenase and the HLA-B27.5 molecule. In addition, (auto)antibodies to a synthetic peptide that contained the HLA-B27.5/klebsiella mimicking epitope have been detected in serum samples from HLA-B27 positive patients with ankylosing spondylitis and Reiter's syndrome. Confirmation of these data is important, because ankylosing spondylitis and Reiter's syndrome have so far been assumed to be 'seronegative' rheumatic diseases. It was, however, not possible to confirm the presence of autoantibodies against the mimicking peptide in serum samples from patients with ankylosing spondylitis and Reiter's syndrome. Serum samples from 81 patients with ankylosing spondylitis, 38 patients with Reiter's syndrome, and 81 healthy blood donors were tested against the 'mimicking peptide' in an enzyme linked immunosorbent assay (ELISA). Some of the serum samples from patients showed high but non-specific binding to the mimicking peptide. A highly significant correlation between binding to plastic coated with the mimicking peptide, to plastic coated with an irrelevant peptide, and even to non-coated plastic was observed. The nature of the serum component(s) in these patient serum samples (and some control serum samples) responsible for the high non-specific binding to plastic remains unclear. It was also shown that antibodies to the HLA-B27 peptide (containing the mimicking epitope) induced in rabbits do not cross react with the klebsiella peptide and vice versa.

Topics: Adult; Aged; Animals; Arthritis, Reactive; Autoantibodies; Cross Reactions; Female; HLA-B27 Antigen; Humans; Klebsiella pneumoniae; Male; Middle Aged; Nitrogenase; Peptides; Rabbits; Sequence Homology, Nucleic Acid; Spondylitis, Ankylosing

Topics: Arthritis, Reactive; Autoantibodies; Cross Reactions; Epitopes; HLA-B27 Antigen; Humans; Klebsiella pneumoniae; Nitrogenase; Spondylitis, Ankylosing

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.

Topics: Amino Acid Sequence; Arthritis, Reactive; Cross Reactions; Epitopes; HLA-B Antigens; HLA-B27 Antigen; Humans; Klebsiella Infections; Klebsiella pneumoniae; Molecular Sequence Data; Nitrogenase; Spondylitis, Ankylosing

Topics: Amino Acid Sequence; Arthritis, Reactive; Autoantibodies; Epitopes; HLA Antigens; HLA-B27 Antigen; Humans; Information Systems; Klebsiella pneumoniae; Molecular Sequence Data; Nitrogenase; Sequence Homology, Nucleic Acid; Spondylitis, Ankylosing