Vaughan Carter

MHC-correlated odour preferences in humans and the use of oral contraceptives.

Previous studies in animals and humans show that genes in the major histocompatibility complex (MHC) influence individual odours and that females often prefer odour of MHC-dissimilar males, perhaps to increase offspring heterozygosity or reduce inbreeding. Women using oral hormonal contraceptives have been reported to have the opposite preference, raising the possibility that oral contraceptives alter female preference towards MHC similarity, with possible fertility costs. Here we test directly whether contraceptive pill use alters odour preferences using a longitudinal design in which women were tested before and after initiating pill use; a control group of non-users were tested with a comparable interval between test sessions. In contrast to some previous studies, there was no significant difference in ratings between odours of MHC-dissimilar and MHC-similar men among women during the follicular cycle phase. However, single women preferred odours of MHC-similar men, while women in relationships preferred odours of MHC-dissimilar men, a result consistent with studies in other species, suggesting that paired females may seek to improve offspring quality through extra-pair partnerships. Across tests, we found a significant preference shift towards MHC similarity associated with pill use, which was not evident in the control group. If odour plays a role in human mate choice, our results suggest that contraceptive pill use could disrupt disassortative mate preferences.

MHC-assortative facial preferences in humans

Individuals tend to choose mates who are sufficiently genetically dissimilar to avoid inbreeding. As facial attractiveness is a key factor in human mate preference, we investigated whether facial preferences were related to genetic dissimilarity. We asked female volunteers to rate the attractiveness of men from photographs and compared these results with individual genotypes at the major histocompatibility complex (MHC). In contrast to previously reported preferences based on odour, we found a non-significant tendency for women to rate MHC-similar faces as more attractive, suggesting a preference for cues to a self-similar MHC in faces. Further analysis revealed that male faces received higher attractiveness scores when rated by women who were MHC-similar than by MHC-dissimilar women. Although unexpected, this MHC-similar facial preference is consistent with other studies documenting assortative preferences in humans, including for facial phenotype.

Donor CD31 genotype impacts on transplant complications after human leukocyte antigen-matched sibling allogeneic bone marrow transplantation.

Mismatch for the adhesion molecule CD31 (PECAM-1) has been associated in some studies with graft-versus-host disease (GVHD), suggesting a role for CD31 as a minor histocompatibility antigen. We examined polymorphisms of the CD31 (PECAM-1) gene in 74 patients and their human leukocyte antigen-matched sibling donors, comparing CD31 genotype with outcomes of occurrence of GVHD and survival using regression analysis. Polymorphisms in codon 125, 563, and 670 are strongly linked forming conserved haplotypes. Donor CD31 (val/asn/gly) haplotype was associated with acute GVHD (P=0.004, odds ratio 7.5). In addition, donor heterozygosity at codon 563 was significantly associated with worse overall survival after correcting for other known variables by regression modeling. Peptide binding predictions support the hypothesis that CD31 could act as a minor histocompatibility antigen. Assessment for CD31 gene status may be of value in pretransplant assessment of bone marrow transplant recipients and donors for prediction of likely transplant-related complications.

A case of acute humoral rejection in liver transplantation: successful treatment with plasmapheresis and mycophenolate mofetil

We present a case of a 23‐year‐old female who underwent orthotopic liver transplantation (OLTx) for biliary atresia, 22 years after a failed Kasai operation. Unusually, her postoperative course was complicated by severe acute humoral rejection. In this case report, we discuss her management as well as the role of plasmapheresis in treating allograft dysfunction secondary to acute humoral rejection in liver transplant patients.

The relevance of donor T cell-directed immunoglobulin G in historic sera in the age of flow cytometry.

Background. Renal transplant recipients with a positive historic cross-match due to donor T cell-directed IgG antibodies are considered to have decreased graft survival, even if their current serum is negative prior to transplantation.With the use of flow cytometric cross-match for testing current sera, false-negative results could be eliminated and the outcome of transplantation in this group of patients could be improved, assuming that immunological memory is effectively controlled with immunosupression. Methods. We reviewed our records to identify those patients who underwent cadaveric renal transplant, with a historic IgG positive cytotoxic T cell cross-match and a current negative flow cytometric T cell cross-match. Results. Eighteen patients underwent cadaveric renal transplant in the face of a historic IgG positive T cell cross-match and a current negative flow cytometric T cell cross-match. In 14 patients treated with cyclosporine-based immunosuppression the 1-, 2-, and 3-year cumulative graft survival rates were 57, 50, and 43%, respectively. Ten of the 14 patients (71%) ultimately lost their grafts. Conclusions. Even with negative flow cytometric cross-match in current serum, a positive historic conventional cross-match suggests a high risk of graft failure.

Incidence of De-Novo Donor Specific Anti-Human Leucocyte Antigen (HLA) Antibodies (DSA) in Simultaneous Pancreas Kidney (SPK) Transplant Patients: A comparison between alemtuzumab and basiliximab based immunosuppression regimes

Introduction De-novo Donor Specific Human Leucocyte Antigen (HLA) Antibodies (DSA) are detrimental to organ transplants. Few studies have explored the incidence of DSA’s and subsequent outcomes after SPK transplant, and none have compared different immunosuppression regimes. The aim of this study was to compare two different immunosuppression regimes (Alemtuzumab versus Basiliximab) with regard to the development of DSA and their long-term outcomes. Materials and Methods We introduced Alemtuzumab for all our SPK recipients from March 2008 onwards along with a Tacrolimus and MMF (from day 7) for maintenance. Prior to this, we used Basiliximab along with our standard immunosuppression regime of a CNI, MMF and steroids. We performed a retrospective analysis of all our SPK transplant patients between 2003 – June 2016. DSA were measured as early (within 2 years) and late (>2 years post-transplantation). HLA antibody testing was performed as per clinical need using a Luminex 200 flow cytometer (Luminex, Inc., Austin, TX). Samples were initially screened for the presence or absence of HLA antibodies using Labscreen mixed HLA antibody screening kits (One Lambda Inc., Canoga Park, CA, USA). For all positive and reactive results, HLA antibody specificities were determined using a combination of Lifecodes ID (Immucor USA) and Labscreen single antigen kits (One Lambda Inc.). Data was analysed using Microsoft Excel 2011 and SPSS 23. Chi-square test was used to compare the groups. Results and Discussion A total of 83 SPK transplants were performed Alemtuzumab (n=53) and Basiliximab (n=30). For early DSA, 20 patients were tested in the Basiliximab group; none developed DSA. In contrast, 34% patients (14 out of 41 tested) in the Alemtuzumab group developed early DSA (p=0.009). Of those 14 patients, 3 (21%) lost their kidney grafts, 6 (43%) lost their pancreas and 3 (21%) eventually died. For late DSA, 18 patients were tested in the Basiliximab group and 3 (17%) were found to be positive. 2/3 patients suffered pancreas graft loss, 1 lost the kidney graft and 1 died as a complication of post-transplant lymphoproliferative disorder. In the Alemtuzumab group, 12 (41%) out of 29 tested developed DSA (p=0.077). Out of those 12 patients, 4 (33%) kidneys and 5 (42%) pancreas were lost and 3 (25%) deaths were recorded. 11 patients (92%) out of the 12 who were positive for late DSA, had early DSA as well. Conclusion Patients on an Alemtuzumab based regime had a significantly higher incidence of early DSA in comparison to a Basiliximab based regime in those patients that were tested. A higher proportion continued to develop late DSA in the Alemtuzumab group. The presence of DSA was associated with very high rates of both pancreas and kidney graft loss.