Susceptibility to and severity of rheumatoid arthritis in multicase families.

Fifteen sibships, each having two or more siblings affected by classical or definite RA were studied. They comprised 31 patients with RA (all in remission) and 21 normal siblings. The total severity index of RA was assessed by clinical and radiological indices. For all the patients the following investigations were carried out: (1) HLA antigens determination for nine antigens at A locus and 15 at B locus and 6 at DR locus; (2) rheumatoid factor. We found: (1) RA disease is genetically controlled and the responsible genes are linked to the HLA system; (2) association between seropositivity and DR4 and DR4/B27 genotypes; (3) significant effect of the genotype DR4/B27 on the age of onset; (4) association between the increase in disease severity both clinical and radiological and DR4/X and DR4/B27 phenotypes. Thus the genetic control is probably composed of two types of genes: disease susceptibility genes and disease severity genes linked to DR4/X and DR4/B27 phenotypes.