Antibodies to β2 microglobulin in the sera of patients with systemic lupus erythematosus

The present study reports the detection of antibodies to β₂ microglobulin in the sera of patients with systemic lupus erythematosus (SLE). Using a Farr-type ammonium sulphate precipitation assay, test sera were reacted with ¹²⁵Iβ₂ microglobulin, and immunoglobulins precipitated by 50% saturated ammonium sulphate. Increased β₂ 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 β₂ microglobulin. Direct validation was done by reacting ¹²⁵Iβ₂ microglobulin with 4 SLE sera having increased ¹²⁵Iβ₂ microglobulin binding activity, and subjecting the reactants to sucrose density gradient ultracentrifugation. Two peaks were obtained, one corresponding to free β₂ microglobulin, and the other to 7S material complexed to β₂ microglobulin. Normal sera demonstrated only one peak corresponding to unbound β₂ microglobulin. Assays of β₂ 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 β₂ microglobulin was demonstrated to be IgG. It was also shown that sera with abnormal β₂ 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.