Antibodies to beta 2 microglobulin in the sera of patients with systemic lupus erythematosus.

Abstract

The present study reports the detection of antibodies to β(2) microglobulin in the sera of patients with systemic lupus erythematosus (SLE). Using a Farr-type ammonium sulphate precipitation assay, test sera were reacted with (125)Iβ(2) microglobulin, and immunoglobulins precipitated by 50% saturated ammonium sulphate. Increased β(2) microglobulin binding activity (normal values: mean±2 sd = 35.5 ±7.8) was detected in 18 of 42 SLE sera. Anti-HLA sera did not reveal increased binding activity, suggesting that the antibody in SLE serum was directed toward free β(2) microglobulin. Direct validation was done by reacting (125)Iβ(2) microglobulin with 4 SLE sera having increased (125)Iβ(2) microglobulin binding activity, and subjecting the reactants to sucrose density gradient ultracentrifugation. Two peaks were obtained, one corresponding to free β(2) microglobulin, and the other to 7S material complexed to β(2) microglobulin. Normal sera demonstrated only one peak corresponding to unbound β(2) microglobulin. Assays of β(2) microglobulin binding activity on protein fractions obtained by Sephadex G200 column chromatography also showed the presence of increased binding activity with 7S fractions. Using a double antibody assay, the 7S material reactive to β(2) microglobulin was demonstrated to be IgG. It was also shown that sera with abnormal β(2) microglobulin binding activity had higher titres of antinuclear antibody compared to those lacking such activity (t = 3.18; P<0.01), indicating the pathogenetic relationship of this antibody to increased disease activity. This antibody may be responsible for some of the abnormalities of cell-mediated function previously described in SLE patients.