Genes on chromosome 14q and their role in the pathogenesis of HLA-B27 associated diseases.
Genetic factors other than HLA-B27 may play a role in the pathogenesis of ankylosing spondylitis (AS), acute anterior uveitis (AAU) and Reiter's syndrome (RS). Studies by Brewerton et al. and Kijlstra et al. showed associations between the MZ phenotype of alpha 1-antitrypsin and the Gm phenotype zafngb of IgG in patients with AAU, who developed AS. The loci for alpha 1-antitrypsin (PI) and Gm allotypes (IGH) are situated on the tip of the long arm of chromosome 14. In the present study we tried to clarify and extend the above studies. In 41 B27+ AAU patients with AS the alpha 1-antitrypsin and Gm phenotype and allotype frequencies were not statistically different from those in B27+ AS patients developing AAU and in B27+ AAU patients without AS, in B27+ AS patients without AAU, B27+ patients with Reiter's syndrome, B27+ patients with low back pain, B27- AAU patients and normal controls. It is therefore unlikely that genes on the tip of chromosome 14 play a role in the pathogenesis of B27 associated diseases. A hypothesis was formed suggesting that a bacterial-derived modifying factor may replace the position of beta 2 microglobulin in the HLA-B27 molecule resulting in an impaired cytotoxic T cell reactivity.
D000483:Alleles; D016918:Arthritis, Reactive / Q000235:genetics* / Q000276:immunology; D002883:Chromosomes, Human, Pair 14; D004198:Disease Susceptibility; D005787:Gene Frequency; D006680:HLA Antigens / Q000235:genetics*; D015796:HLA-B27 Antigen; D006801:Humans; D010641:Phenotype; D013167:Spondylitis, Ankylosing / Q000235:genetics* / Q000276:immunology; D014606:Uveitis, Anterior / Q000235:genetics* / Q000276:immunology
D006680:HLA Antigens; D015796:HLA-B27 Antigen