Demonstration of Electrophoretic Heterogeneity of Serum β2‐Microglobulin in Systemic Lupus Erythematosus and Rheumatoid Arthritis: Evidence against Autoantibodies to β2‐Microglobulin

Abstract

A sensitive crossed radioimmunoelectrophoretic method (CRIE), originally developed to study lymphocyte-associated β₂-microglobulin (β₂m), was applied in the study of serum β₂m in patients with systemic lupus erythemutosus (SLE) and rheumatoid arthritis (RA). In six of seven patients with SLE and nineteen of twenty-seven patients with RA a considerable elec-trophoretic heterogeneity of serum β₂m was found. In addition to the normally seen symmetric β₂m precipitate, a β₂ precipitate exhibiting complete immunochemical identity was found in the α-electrophoretic region. Binding of isolated ^I25l-labelled β₂m to the abnormal precipitate was demonstrated in crossed immunoelectrophoresis. After gel filtration of sera exhibiting the above-mentioned β₂m binding, all β₂m was eluted in low molecular weight fractions corresponding to free β₂m. By application of appropriate antisera and a glycoprotein-binding lectin in intermediate gels in CRIE, it was shown that the possible β₂m-binding ligand is not an antibody, not a major constituent of normal human serum, and not unmodified HLA alloantigen. The abnormality was not restricted to patients with high disease activity but was found more frequently and was more pronounced (mean score 1.6 arbitrary units against 0.57 arbitrary units, P < 0.01) in such patients. Thus our data exelude the possibility that autoantibodies to β₂m were present in serum from patients with SLE and RA.