Rapid and strong de novo donor-specific antibody development in a lung transplant recipient: Short communication/case report.

A 66-yo female patient (typed B*39:01, 44:02) underwent first left single lung transplant (typed B*81:01, 15:17) on 02/07/2016 with negative for DSA in current and historical samples. On 02/17/2016 strong de novo DSA (MFI=15,200, C1q+) to B81 were detected. The recipient has two children typed B*07:02, 44:02 B*27:03, 39:01, and had received multiple vaccinations. Twinrix, Zostavax and MMR vaccines contain viruses grown on live human lung fibroblasts (MRC-5, typed B*07:02, 44:02, and WI-38, typed B*08:01, 58:01). Each dose of vaccine used for injection is known to contain protein components of fibroblasts including HLA. Most likely rapid de novo DSA development is due to booster effect produced by five exposures to mismatched B locus alleles which share the following epitopes: 70IAQ, 65QIA, 65QIA+76esn, 69aa+80n, and 163ew+73te. The later three consist of paired non-self and self eplets. Although likelihood of bystander effect produced by multiple vaccinations is low its impact cannot be ruled out.

Analysis of anti-HLA antibodies in sensitized kidney transplant candidates subjected to desensitization with intravenous immunoglobulin and rituximab.

BACKGROUND: Preexisting donor-specific antibodies against human leukocyte antigens are major risk factors for acute antibody-mediated and chronic rejection of kidney transplant grafts. Immunomodulation (desensitization) protocols may reduce antibody concentration and improve the success of transplant. We investigated the effect of desensitization with intravenous immunoglobulin and rituximab on the antibody profile in highly sensitized kidney transplant candidates. METHODS: In 31 transplant candidates (calculated panel-reactive antibody [cPRA], 34%-99%), desensitization included intravenous immunoglobulin on days 0 and 30 and a single dose of rituximab on day 15. Anti-human leukocyte antigen antibodies were analyzed before and after desensitization. RESULTS: Reduction of cPRA from 25% to 50% was noted for anti-class I (5 patients, within 20-60 days) and anti-class II (3 patients, within 10-20 days) antibodies. After initial reduction of cPRA, the cPRA increased within 120 days. In 24 patients, decrease in mean fluorescence intensity of antibodies by more than 50% was noted at follow-up, but there was no reduction of cPRA. Rebound occurred in 65% patients for anti-class I antibodies at 350 days and anti-class II antibodies at 101 to 200 days. Probability of rebound effect was higher in patients with mean fluorescence intensity of more than 10,700 before desensitization, anti-class II antibodies, and history of previous transplant. CONCLUSIONS: The desensitization protocol had limited efficacy in highly sensitized kidney transplant candidate because of the short period with antibody reduction and high frequency of rebound effect.