Rheumatoid factors from patients with rheumatoid arthritis react with Des-Lys58-β2m, modified β2-microglobulin

Abstract

Ten polyclonal IgM rheumatoid factor (RF) preparations, affinity-purified from IgG columns, from patients with rheumatoid arthritis were studied for their ELISA reactivity with native β2m in parallel with Lys58-cleaved β2m and Des-Lys58-β2m, the latter representing cleavage products of the native molecule present in some pathologic human sera. Most RF showed positive reactions with the native form of β2m but reduced reactivity for the cleaved forms of β2m. Reactions between cleaved β2m and RF, in solution, were demonstrated by inhibition of RF binding to native β2m by preincubation with a range of concentrations of Des-Lys58-β2m. By contrast, eight of nine murine MoAbs to human β2m showed approximately equivalent binding to native β2m, Lys58-cleaved β2m, and Des-Lys58-β2m. Reactions between individual human RF and the altered forms of β2m (Lys58-cleaved β2m and Des-Lys58-β2m) appeared to parallel the previously determined β2m single amino acid specificities, in that RF showing strong reactivity with Lysine 58 also showed a significant diminished reactivity with the Des-Lys58-β2m lacking the critical lysine residue. The present studies demonstrate that while human RF react with Lys58-cleaved β2m or Des-Lys58-β2m, preferential reactivity is observed for native unaltered β2m.