P046

• Published in: Human immunology 2014-10, Vol.75, p.82-82
• Main Authors: Habig, Dennis F, Gaspari, Justine L, Mowery, Carrie L, Casey, Heather A, Fisher, Carolyn L, Maybach, Margaret A, Hess, Jean A, Goss, Kimberly J, Kadry, Zakiyah, Ghahramani, Nasr, Shah, Riaz Ali, Domen, Ronald E, Shike, Hiroko
• Format: Article
• Language: English
• Subjects: Allergy and Immunology
• ISSN: 0198-8859
• DOI: 10.1016/j.humimm.2014.08.108

Aim We report three post-kidney transplant (Tx) patients who developed de novo HLA antibody, possible donor specific antibody (DSA) to trans-encoded donor HLA-DQ alpha–beta heterodimers (a combination of a beta-chain from one DQ gene and an alpha-chain from the other DQ gene). Methods Patients/donors were typed for HLA-A, B, C, DRB1, DRB3/4/5, and DQB1. DQA1 was typed since 2010. DQA1 was predicted by gene association when unavailable. HLA antibody was tested by Labscreen PRA/Single Antigen (One Lambda). Patients were monitored for DSA and creatinine after kidney-transplantation. Results De novo DSA was detected in 54 out of 349 post-Tx patients. In addition, de novo HLA antibody was detected in three patients with specificity consistent with predicted donor DQ trans-hetero-dimers, possible DSAs. Case 1 (50 y/o female) received a kidney from a living donor with negative CDC XM (2005). Donor was DR11 DR7 DQ2 DQ7 (DQ2.2 DQ7.5). Creatinine was 1.2 and PRA was 0% for 3.8 years. Strong anti-DQ2.5 (C1q positive) was first detected in the post-Tx year 4. DQ2.5 can be a donor antigen: a combination of DQ2 and DQA1∗ 05 (DQ7.5). Currently, patient is 9 years post-Tx with progressive allograft nephropathy and creatinine is 4.9. Case 2 (21 y/o male) received a kidney from a living donor with negative CDC XM (2006). Donor was DR4 DR7 DQ2 DQ8 (DQ2.2 DQ8.3). Baseline creatinine was 1.6 and PRA was 0% for 3 years. In the post-Tx year 5, creatinine increased to 2.3, de novo anti-DQ2.3 antibody (C1q negative) was detected, and biopsy showed diffuse C4d+ borderline cellular rejection. Despite the treatment (plasmapheresis, IVIg, rituximab, and steroid), anti-DQ2.3 persisted and the graft was lost in the post-Tx year 7. Case 3 (4 y/o female) received a kidney from the father with negative CDC XM (2002). Donor was DR4 DR8 DQ4 DQ8 (DQ4.4 DQ8.3). For 8 years, creatinine was 0.9 and PRA was 0%. Grade IA rejection was detected in the post-Tx year 12 with increased creatinine 1.4, and de novo anti-DQ4.3 antibody (C1q negative). Graft function improved with steroid treatment, and has remained stable with weak anti-DQ4.3. Conclusions Of the three patients with suspected DSA to donor DQ trans-heterodimer, two patients presented declining graft function consistent with chronic antibody-mediated rejection. Donor DQA1 typing is important in recognizing DQ DSA.