Genetics of the spondarthropathies.
Recent investigation of the possible role of bacteria in the pathogenesis of AS has provided very interesting data. What is at present lacking is a clear demonstration that the findings point to the actual mechanisms involved in the initiation of the disorder. Rapid progress in three related areas of research gives hope that, in the relatively near future, the genetic basis for susceptibility to AS will be elucidated. These are the demonstration of the detailed structure of an HLA class I molecule, of the primary amino acid structure of B27 heavy chain with its subtypes, and of the nature of the interaction between foreign proteins and MHC molecules which leads to antibody and cytotoxic cell responses. It is just possible that the B27 molecules have a disease-promoting capability because of some structural characteristic independent of their antigen binding site. However, it may perhaps be considered more likely that it is the propensity of the specific antigen-binding site itself to bind to a particular group of antigenic peptides that will explain the susceptibility of B27-positive individuals to several clinical disorders. The ability to study the properties of antigenic epitopes which preferentially bind to the very variable binding site of different MHC molecules raises the possibility of revealing the antigenic structures which bind to B27 molecules in patients with AS. This could in turn lead to the source of these antigens in the environment. There has been a tendency to assume that one simple model will explain all the B27-associated disorders but it may be preferable to keep an open mind about the possibility that the mechanisms involved in AS, in the bacteria-induced acute arthropathies and in acute anterior uveitis may not be identical. At the same time, there is a need to continue further direct investigation of the role of microbiological agents in AS both in vitro and in vivo, as ultimately it is most likely that, by blocking the effects of such agents as may be shown to be involved, progress in our ability to influence the progress of the disease in a fundamental way will be achieved. There is still little information as to how the tissues involved in AS come to be the particular targets of the pathological process and currently proposed theories of pathogenesis have not yet provided very satisfactory answers to this problem.
Woodrow
J C
JC
D000595:Amino Acid Sequence; D001168:Arthritis / Q000235:genetics*; D004198:Disease Susceptibility; D008040:Genetic Linkage; D015235:HLA-B Antigens / Q000235:genetics*; D015796:HLA-B27 Antigen; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics; D008969:Molecular Sequence Data; D011565:Psoriasis / Q000235:genetics; D013167:Spondylitis, Ankylosing / Q000235:genetics*; D008061:Whipple Disease / Q000235:genetics
D015235:HLA-B Antigens; D015796:HLA-B27 Antigen