Sensitization following Thymoglobulin and Atgam rejection therapy as determined with a rapid enzyme-linked immunosorbent assay

Monoclonal and polyclonal anti-thymocyte preparations play an important rol e in solid organ transplant immunosuppression. While it is generally accept ed that blocking anti-idiotypic antibodies can decrease the efficacy of ret reatment with mouse monoclonal antibody preparations, sensitization levels and subsequent effects on treatment efficacy are less clear for polyclonal preparations. Serum samples were obtained from 148 patients participating i n a multicentre, double-blind randomized phase III trial comparing Atgam (P harmacia Upjohn, horse anti-thymocyte globulin) with Thymoglobulin (SangSta t Medical Corporation, rabbit anti-thymocyte globulin). Recipients of a fir st or second renal allograft undergoing biopsy proven acute rejection were randomized to treatment with Atgam or Thymoglobulin. Serum samples were ana lysed for presence of anti-Thymoglobulin and anti-Atgam antibodies. Sensiti zation levels to rabbit IgG in Thymoglobulin-treated patients (68%, n = 54) was similar to sensitization to horse IgG in Atgam-treated patients (78%, n = 54) (two-sided p value = 0.4, Fisher's exact test), although Atgam-trea ted patients remained sensitized longer (at day 90, 67% anti-horse IgG posi tive in Atgam treated vs 24% anti-rabbit IgG in Thymoglobulin positive,p = 0.001). No difference was seen in the production of a crossreactive respons e. Similarly, sensitization had no significant effect on treatment success or failure. For Thymoglobulin-treated patients, the sensitization rate in s uccessfully treated patients was 68%, while in patients with treatment fail ures it was 71% (p = not significant, ns). In Atgam-treated patients, the s ensitization rate in successfully treated patients was 82%, while in patien ts with treatment failures it was 67% (p = ns). In conclusion, patients tre ated with Thymoglobulin and patients treated with Atgam exhibited similar l evels of sensitization, presensitization and crossreactive sensitization, a lthough the anti-horse response was longer lasting; neither presensitizatio n nor treatment-induced sensitization appeared to effect treatment efficacy .