Rheumatoid factors from patients with rheumatoid arthritis react with Des-Lys58-beta 2m, modified beta 2-microglobulin.
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 beta 2m in parallel with Lys58-cleaved beta 2m and Des-Lys58-beta 2m, 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 beta 2m but reduced reactivity for the cleaved forms of beta 2m. Reactions between cleaved beta 2m and RF, in solution, were demonstrated by inhibition of RF binding to native beta 2m by preincubation with a range of concentrations of Des-Lys58-beta 2m. By contrast, eight of nine murine MoAbs to human beta 2m showed approximately equivalent binding to native beta 2m, Lys58-cleaved beta 2m, and Des-Lys58-beta 2m. Reactions between individual human RF and the altered forms of beta 2m (Lys58-cleaved beta 2m and Des-Lys58-beta 2m) appeared to parallel the previously determined beta 2m single amino acid specificities, in that RF showing strong reactivity with Lysine 58 also showed a significant diminished reactivity with the Des-Lys58-beta 2m lacking the critical lysine residue. The present studies demonstrate that while human RF react with Lys58-cleaved beta 2m or Des-Lys58-beta 2m, preferential reactivity is observed for native unaltered beta 2m.
Williams
R C
RC
Department of Medicine, University of Florida School of Medicine, Gainesville 32610-0221.
Nissen
M H
MH
Malone
C C
CC
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D002417:Cattle; D002846:Chromatography, Affinity; D003429:Cross Reactions / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology; D006168:Guinea Pigs; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology; D008969:Molecular Sequence Data; D011817:Rabbits; D012217:Rheumatoid Factor / Q000276:immunology* / Q000302:isolation & purification; D001613:beta 2-Microglobulin / Q000276:immunology
D000911:Antibodies, Monoclonal; D000939:Epitopes; D007075:Immunoglobulin M; D001613:beta 2-Microglobulin; C081768:beta 2-microglobulin, des-lysyl(58)-; D012217:Rheumatoid Factor