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Mice of inbred strains immunized with simple antigens can produce antibodies that share similar V regions, which result in serologic similarities called cross-reactive idiotypes (CRI). In this study, we considered the possibility that IgA-deficient humans, who are continuously immunized via the intestinal tract by dietary protein, might also produce antibodies sharing CRI. For this, anti-casein antibodies were isolated from the blood of 16 adult IgA-deficient donors (4 Finns and 12 North Americans) and an autologous anti-anti-casein from the blood of one of the Finnish donors. In addition, a heterologous anti-anti-casein was raised to the casein-anti-casein immune complexes of this donor. Comparing the activities of the two anti-idiotypes, it was found that both bind anti-casein in the region of the antigen binding site, but that each binds additional determinants not located within this region, with the heterologous reagent having more affinity for these latter determinants than the autologous anti-idiotype. Using both reagents in enzyme-linked immunosorbent assay inhibition assays, extensive cross-reactivities between anti-caseins were demonstrated. Using the autologous anti-idiotype, 5 of 16 anti-caseins were found to share CRI, and with the heterologous reagent 12 of 16 shared CRI. In both assays, the anti-caseins of Finnish donors displayed more cross-reactivity than those derived from Northern American donors. These studies show that specific, commonly shared CRI can be identified in this human system in which antibodies are raised as a result of natural immunization across the gastrointestinal mucosa.

Cross-reactive idiotypes in immunoglobulin A-deficient sera.