FREQUENCY OF MHC CLASS II REACTIVE ANTIBODIES IN TRANSPLANT PATIENTS.
PK Hennessy, PW Adams, RP Pelletier, CG Orosz
The Ohio State University Medical Center, Columbus, OH.

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We have determined the incidence of humoral allosensitization in primary renal and renal pancreas allograft recipients in our transplant program. To identify pre-transplant alloantibodies, sera from 183 random selected patients awaiting transplant were tested. The presence of circulating MHC Class I and Class II alloantibodies was detected using One Lambda FlowPRA Class I and Class II beads. To analyze post-transplant alloantibodies, randomly obtained sera from 169 transplant recipients were similarly tested. None of the patients who were tested post-transplant had detectable pre-transplant alloantibodies, and all final crossmatches were negative. In the pre-transplant group, 19%(35/183) of patients' sera contained alloantibodies; 8% (14/183) were directed at Class I, 8%(15/183) were directed at both Class I and Class II, and only 3%(6/183) were directed at Class II. Sera obtained post-transplant were divided into an early post-tx group (>6 mos <2 yrs) and a late post-tx group (>2 yrs). In the early post-tx group, 30%(29/96) of the patient's sera exhibited alloantibodies; 5%(5/96) were directed at Class I only, 5%(5/96) were directed at both Class I and Class II, and 20%(19/96) were directed at Class II only. In the late post-transplant group, 31%(18/59) of the patients' sera exhibited alloantibodies. However, only 2%(1/59) were directed at Class I, whereas 29%(17/59)were directed at Class II. None of the late post-tx patients displayed both Class I and Class II-reactive alloantibodies. These data demonstrate that: 1) In the pre-transplant population, the incidence of alloantibody sensitization is 19%, and the antibodies directed at MHC Class II are relatively rare.; 2) In the early post transplant period about 30% of the patients become allosensitized, and the incidence of anti-MHC class II alloantibodies is about 20% ; 3) By two years after transplant, the same number (30%) of transplant recipients are allosensitized, but virtually all the alloantibodies are directed at MHC Class II. The clinical significance of these MHC Class II alloantibodies is currently unknown. It is not clear whether this apparent post-transplant shift to MHC Class II-reactive alloantibodies reflects persistent dominant immune stimulation by allogenic MHC Class II molecules, and/or the differential survival of allografts in patients who develop anti-MHC Class II alloantibodies.