In a population survey in The Netherlands we investigated 6584 individuals for the presence of rheumatoid diseases and their determinants. We observed no overall association of rheumatoid arthritis (RA) with HLA-DR4 or GM. This result is in contrast to the marked association of HLA-DR4 with RA found in studies based mainly on hospital rheumatology clinics. The findings thus suggest a genetic basis for the disease heterogeneity. A study of 16 multicase RA families showed a co-segregation of RA with the DR4 carrying haplotype from the unaffected parent, whereas the non-DR4 haplotype was preferentially segregating to the healthy siblings (p = 0.001). These data suggest that HLA-DR4 is associated with disease susceptibility rather than with a disease modifying factor. In a further attempt to define a genetic basis for disease heterogeneity we compared five well-defined clinical groups of patients with RA. Although the frequency of HLA-DR4 was significantly elevated in all patient groups as compared to healthy controls, we observed a preferential association of HLA-DR4 with severe extra-articular manifestations as compared to patients without extra-articular manifestations (p = 0.002). These results provide an immunogenetical basis for the disease heterogeneity observed in RA and further extend the immunological analogy between RA and leprosy.
BT - Disease markers C1 - http://www.ncbi.nlm.nih.gov/pubmed/3502562?dopt=Abstract DA - 1986 Jun IS - 1-2 J2 - Dis. Markers LA - eng N2 -In a population survey in The Netherlands we investigated 6584 individuals for the presence of rheumatoid diseases and their determinants. We observed no overall association of rheumatoid arthritis (RA) with HLA-DR4 or GM. This result is in contrast to the marked association of HLA-DR4 with RA found in studies based mainly on hospital rheumatology clinics. The findings thus suggest a genetic basis for the disease heterogeneity. A study of 16 multicase RA families showed a co-segregation of RA with the DR4 carrying haplotype from the unaffected parent, whereas the non-DR4 haplotype was preferentially segregating to the healthy siblings (p = 0.001). These data suggest that HLA-DR4 is associated with disease susceptibility rather than with a disease modifying factor. In a further attempt to define a genetic basis for disease heterogeneity we compared five well-defined clinical groups of patients with RA. Although the frequency of HLA-DR4 was significantly elevated in all patient groups as compared to healthy controls, we observed a preferential association of HLA-DR4 with severe extra-articular manifestations as compared to patients without extra-articular manifestations (p = 0.002). These results provide an immunogenetical basis for the disease heterogeneity observed in RA and further extend the immunological analogy between RA and leprosy.
PY - 1986 SP - 29 EP - 33 T2 - Disease markers TI - Genetic heterogeneity of rheumatoid arthritis. VL - 4 SN - 0278-0240 ER -