RHEUMATOID FACTORS FROM PATIENTS WITH RHEUMATOID-ARTHRITIS REACT WITHDES-LYS(58)-BETA-2M, MODIFIED BETA-2-MICROGLOBULIN

Ten polyclonal IgM rheumatoid factor (RF) preparations, affinity-purif ied from IgG columns, from patients with rheumatoid arthritis were stu died for their ELISA reactivity with native beta2m in parallel with Ly s58-cleaved beta2m and Des-Lys-58-beta2m, the latter representing clea vage products of the native molecule present in some pathologic human sera. Most RF showed positive reactions with the native form of beta2m but reduced reactivity for the cleaved forms of beta2m. Reactions bet ween cleaved beta2m and RF, in solution, were demonstrated by inhibiti on of RF binding to native beta2m by preincubation with a range of con centrations of Des-Lys58-beta2m. By contrast, eight of nine murine MoA bs to human beta2m showed approximately equivalent binding to native b eta2m, Lys58-cleaved beta2m, and Des-Lys58-beta2m. Reactions between i ndividual human RF and the altered forms of beta2m (Lys58-cleaved beta 2m and Des-Lys58-beta2m) appeared to parallel the previously determine d beta2m single amino acid specificities, in that RF showing strong re activity with Lysine 58 also showed a significant diminished reactivit y with the Des-Lys58-beta2m lacking the critical lysine residue. The p resent studies demonstrate that while human RF react with Lys58-cleave d beta2m or Des-Lys58-beta2m, preferential reactivity is observed for native unaltered beta2m.