P045

• Published in: Human immunology Vol. 75; p. 81
• Main Authors: Waybill, Mary M, Narins, Seth C, Scott, Robert C, Yang, Harold C
• Format: Journal Article
• Language: English
• Published: 01.10.2014
• Subjects: Allergy and Immunology
• ISSN: 0198-8859; 1879-1166
• DOI: 10.1016/j.humimm.2014.08.107

Aim The alloantibody response in solid organ transplantation is felt to be durable and long lasting. The durability of this response is appreciated in pretransplant patients where alloantibody can only be removed by plasmapheresis in combination with bortezomib, a proteasome inhibitor indicated for patients with relapsing multiple myeloma. We hereby report a cohort of post-transplant patients with donor specific antibody that has been successfully mitigated using increased antimetabolite alone. Methods Since October 2008, annual screening and testing for renal dysfunction has identified 238 renal transplant patients with donor-specific antibody, as characterized by Luminex single antigen bead interrogation; 114 patients demonstrated clinically significant DSA, with SFI > 100,000. A retrospective analysis of this group was performed to identify those patients who were treated with increased antimetabolite therapy only and who demonstrated significant decrease in DSA to SFI < 50,000. Serum creatinine levels, mycophenolate area-under-the-curve results, (MPA AUC) increased mycophenolate dosages as well as HLA loci were also assessed. Results Of the 114 patients with clinically significant DSA, 17 (15%) were noted to have significantly decreased SFI with intensified medical therapy only. MPA AUC was assessed after change in medical regimen. Mean values and ranges are summarized: Decrease in DSA levels. Initial Posttreatment SFI 154,684 (99,679–402,188) 29,022 (0–51,644) Creatinine (mg/dl) 1.80 (0.9–4.0) 1.80 (1.0–6.0) MPA AUC – 80.5 (30–133) MMF Dosage (mg/d) 1125 (500–3000) 1700 (1000–3000) Analysis of HLA loci demonstrated DSA at A(2 patients), DR (3 patients) and DQ (12 patients). Conclusions Increased medical immunosuppressive therapy alone may be sufficient to decrease clinically significant DSA levels and to ensure stable renal function. This is often achieved through early detection of DSA formation and optimization of antimetabolite dosage using MPA AUC measurement. Class II HLA loci are most frequently associated with DSA formation, particularly at the DQ locus, suggesting that more frequent monitoring of patients with known Class II mismatches may be beneficial. H.C. Yang: Speaker’s Bureau; Company/Organization; Novartis.