Post-transplant antibody (Ab) to donor HLA is associated with reduced graft survival, but it is unknown if some HLA antigens are more likely to induce an antibody response. We examined Ab data from 273 sequential renal Tx patients with post-Tx Ab, for the frequency, specificity, and strength of their antibodies.

Sera were tested with single antigen beads and analyzed for antibodies to HLA-A, -B, -DRB1, -DRB3-5, and -DQB antigens. The frequency of response to mismatched antigens was tabulated for cases in which there were at least 20 incidents of the mismatch. Ab strength was assessed for all antibodies.

The mean frequencies of patients with antibody to mismatched antigens (MMs) were 49.0%, 34.3%, 36.9%, 50.8%, and 54.9% for A, B, DRB1, DRB3-5, and DQB antigens, respectively. The percentages of Abs to MMs, that were of flow cytometric crossmatch (XM) strength or greater, were 53.6% (A), 48.7% (B), 36.3% (DRB1), 66.7% (DRB3-5), and 58.5% (DQB), approximately proportional to the frequency of response. The percentage of XM strength antibodies to 3rd party (non-donor) antigens was approximately the same for A, DRB1, and DQ antigens (49.5%, 40.7%, and 55.7%) but was greater for B antigens (61.6%) and lower for DRB3-5 antigens (40%). For 261 of 265 cases where XM strength Ab was to 3rd party antigens, the 3rd party antigen was crossreactive with a mismatched antigen. That is, strong Abs to some antigens are induced more often by a crossreactive antigen than by the antigen itself.

It is thought that MMs that are crossreactive with a patient's own antigens may fail to induce a humoral response or induce a weaker response. Of 932 instances in which there was no antibody to a mismatch, the mismatched antigen was crossreactive with the patient’s antigens in only 345 (37%) cases. However, this varied by locus ranging from an incidence of 19.8% for DRB1 to 54% for A antigens. In 459 instances of antibody to a mismatched antigen that was crossreactive with an antigen in the patient, the strength of response was below XM level 58.8% of the time.

Conclusions. Absence of antibody to mismatched antigens is not proof of lack of humoral sensitization. However, as all patients were sensitized, differences in the frequencies and strengths of Ab response to MMs suggests differences in antigen immunogenicity. The presence of an antigen in the patient’s phenotype that is crossreactive with a mismatch does not appear to abrogate response to the mismatch but may reduce the strength of response to the mismatched antigen.

Leffell, M.: Other, Hologics, Travel Funds. Zachary, A.: Other, Thermo Fisher, Honorarium.

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