DETECTION OF IGA ANTI-OKT3 ANTIBODIES IN OKT3-TREATED TRANSPLANT RECIPIENTS

Murine OKT3 monoclonal antibodies function as an immunosuppressant dru g for organ transplant recipients. A contraindication to retreatment m ay develop, however, because a high proportion of OKT3-treated patient s form anti-OKT3 antibodies. Previous data have shown that only antiid iotypic IgG antibodies can negate the beneficial effect of the drug. E ighty-two OKT3-treated transplanted patients were tested by ELISA for IgG, IgM, and IgA anti-OKT3 antibodies and compared with 200 controls. The anti-OKT3 antibody-positive sera were screened additionally by fl ow cytometry for the presence of antiidiotypic activity by measuring O rtho OKT3-FITC activity on a CD3-positive cell line, Jurkat, before an d after incubation with serial dilutions of patient and control sera. Forty-four of 82 patients developed antibodies to OKT3, 20 manifested IgG, 20 produced both IgG and IgA, and 4 IgA only, We never detected I gM anti-OKT3, Of the 44 anti-OKT3-positive patient sera, 25 showed ant iidiotypic specificity. Two IgG/IgA anti-OKT3-positive patient sera we re IgG-depleted by Protein G. Both continued to exhibit antiidiotypic IgA activity, lgA anti-OKT3 was associated with low serum OKT3 levels and lack of ability of OKT3 to lower total CD3 cell numbers to therape utic levels. This is the first report of IgA anti-OKT3 antibody in tra nsplant recipients. Isotype IgA anti-OKT3 was observed in 54% of the p atients whose sera tested positive for anti-OKT3 by ELISA. The IgG/IgA anti-OKT3-positive patient sera tested continued to exhibit antiidiot ypic OKT3 reactivity when depleted of IgG. We urge that OKT3-treated p atients be monitored routinely for IgA anti-OKT3 antibodies to avoid t he expense and potential complications of retreatment with this drug i n sensitized patients.