U.C.L.A. Rheumatology Pathophysiology of Disease Course Lecture,
Second Year Medical School 1997

  
 
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Rheumatoid Arthritis     Page 13
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       RA has a worldwide distribution and in certain ethnic groups the genetic factors have been well worked out. It appears that there is an epitope commonly found on the HLA-DR4 haplotype which is strongly associated with predisposition for the more severe expressions of this disease. This epitope may be shared with other HLA haplotypes so that some patients with RA may be HLA-DR4 negative and yet still possess the disease-associated epitope.
       The shared epitope that promotes susceptibility to RA codes for glutamine-leucine-arginine-alanine-alanine or glutamine-arginine-arginine-alanine-alanine in the third hypervariable region of the beta chain of the Class II MHC molecule (figure 3-4).       Occasionally several family members are afflicted with RA and the disease is more common among monozygotic twins of RA patients.
      Despite decades of intensive study no environmental factor has been found which provokes the onset of RA. Stress, nutrition, weather changes, and pregnancy have all been associated with relapses and remissions of the disease.		    
 
Figure 3. A schematic drawing of HLA-DR4 is depicted in the surface of an antigen presenting cell. The disease associated epitope is shown in red. Click thumbnail figure to view full graphic. jpeg 219 x 164 pixels 9kbs freehand 3dstudio max
Click Picture or here for larger slide and further discussion (640 x 480) 44kb
 
 
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