C3B RECEPTOR (CR-1) GENOMIC POLYMORPHISM IN RHEUMATOID-ARTHRITIS - LOW RECEPTOR LEVELS ON ERYTHROCYTES ARE AN ACQUIRED PHENOMENON

The number of complement receptor 1 (CR1, CD35) molecules on erythrocy tes is genetically determined by two codominant alleles. The numerical expression of CR1 on erythrocytes correlates with a HindIII-RFLP of C R1 gene using CR1-1, a complementary DNA probe. We have found low CR1 on erythrocytes in patients with rheumatoid arthritis (RA) in an India n population. Low levels in RA patients may be acquired or genetically determined. Fifty-two patients with RA, 48 nonrelated healthy subject s and 19 consanguineous relatives of patients were genotyped. CR1 numb ers on erythrocytes were quantitated by the enzyme-linked immunosorben t assay using monoclonal anti-CR1 antibody. Normal subjects and patien ts were followed up for a period of 6 months to evaluate the stability of their CR1 expression. The gene frequency for allele H and L (7.4- and 6.9-kb HindIII restriction fragment, respectively), which correlat ed with high and low expression of CR1 on erythrocytes was 0.77 and 0. 23 in the normal controls. Gene frequency in RA patients was 0.78 and 0.22 for H and L allele, which did not differ significantly from eithe r controls or relatives (0.80 and 0.20 for H and L allele, respectivel y). However, RA patients expressed fewer CR1 on erythrocytes within ea ch genotype than their relatives and controls. CR1 on erythrocytes wer e found to be stable in consecutive samples in controls. In RA patient s, the number varied between low and high during the course of the dis ease. The variation in number was significantly correlated (p < 0.05, r = -0.85 to -0.98) with disease activity as monitored by erythrocyte sedimentation rate. Our results suggest that low levels of CR1 on eryt hrocytes in patients with RA are not inherited, rather they are acquir ed during the course of the disease.