Low median fluorescence intensity could be a nonsafety concept of immunologic risk evaluation in patients with shared molecular eplets in kidney transplantation Alexandre Bosch a , Santiago Llorente b , Julio A. Diaz a , Gema Salgado a , Manuela LÔpez a , Francisco Boix a , Ruth LÔpez-HernÂndez a , MarÎa J. GonzÂlez-Soriano b , JosÊ A. Campillo a,c , MarÎa R. Moya-Quiles a,c , Noelia Perez-Lopez a , Alfredo Minguela a,c , Luisa Jimeno b , MarÎa R. A ´ lvarez-LÔpez a,c , Manuel Muro a,c, * a Department of Immunology, University Hospital Virgen, Arrixaca, 30120 Murcia, Spain b Department of Nephrology, University Hospital Virgen, Arrixaca, 30120 Murcia, Spain c Centro de Investigaciòn Biomèdica en Red de Enfermedades Hepàticas y Digestivas, University Hospital Virgen, Arrixaca, 30120 Murcia, Spain ARTICLE INFO Article history: Received 2 December 2011 Accepted 27 February 2012 Available online 6 March 2012 Keywords: Kidney transplant Median fluorescence intensity Epitopes Cross-matching HLA antibodies ABSTRACT Human leukocyte antigen (HLA) antibodies are usually “epitope” and not “antigen” specific. This work presents an interesting case concerning Luminex median fluorescence intensity (MFI) levels in antibodies considered low risk (1,000), but producing humoral rejection. These low-titer antibodies could play an important role in transplantation. A 42-year-old woman was retransplanted with a deceased donor with negative complement-dependent cytotoxicity cross-matching. Our patient was pretransplant (PrT) sensi- tized to HLA antigens (single antigens (SA) = 31%) for 1 previous transplant. Thus, the formerly detected sensitized antigens were A32, A30, A31, cross-reacting group 5C, and DQ3 with a MFI max  4,127. In the posttransplantation period (PTP), the patient exhibited important instability in renal function and we detected an increased SA percentage (61%) with MFI max = 15,029 (A*32) with other antigens (detected with a low PrT MFI [1,000]) as anti-A*03 (MFI max = 13,301) and anti-A*11 (MFI max = 13,714) specificities. Anti-A*03 was a donor-specific antibody (DSA). Renal biopsy was compatible with humoral rejection. The patient was pulsed with methylprednisolone, plasmapheresis, and intravenous immunoglobulin without improvement. Thus, we added anti-CD20 and the initial clinical response was highly favorable. Biopsies resulted in suggestive rejection reversion. MFI A*03 DSA decreased to 6,908 and later to MFI max = 5,505. After a 6-month PTP, the patient is well with MFI max = 3,124. It was possible to define exactly the potential immunizing epitope eplets whose recognition determined the specific antibody production. A*32:01, A*30: 01, A*31:01 (detected PrT), A*11:01, and A*03:01 (detected PTP) alleles have several shared eplets (62QE, 70AQS, and 76VGT), with 62QE being the only eplet present on all alleles. In conclusion, low MFI levels in antibodies considered low risk could be important in posttransplant humoral rejection, although the pa- tient’s renal function can be restored. Thus, specific shared eplets should always be investigated with respect to previous transplant mismatches.  2012 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved. 1. Introduction The donor-specific human leukocyte antigen (HLA) antibody (DSA) response of recipients to a renal allograft is not fully under- stood [1]. Until recently, it has been difficult to detail the evolution of HLA antibodies after transplantation because the methods used to measure HLA antibody levels were not sensitive and cumber- some. Particularly in antibody screening, newer serum screening methods (i.e., Luminex assay) have greatly enhanced the detection and specificity analysis of anti-HLA antibodies in sensitized patients [2–5]. In this sense, HLA antibodies are usually “epitope” and not “anti- gen” specific. Patients who lose a graft develop wide antibody patterns specific for the HLA molecules sharing the donor-mismatched epitopes (i.e., cross-reacting groups). Luminex bead technology helps not only in the identification of antibody specificities but also in the identification of these potential antibody epitopes. Different protocols have recently emerged using B lymphocyte– depleting molecules (anti-CD20), intravenous immunoglobulin (IVIG), and plasmapheresis to prevent and treat humoral rejection [3,6]. Sensitive DSA screening techniques have also emerged, lead- * Corresponding author. E-mail address: manuel.muro@carm.es (M. Muro). Human Immunology 73 (2012) 522–525 Contents lists available at SciVerse ScienceDirect 0198-8859/12/$36.00 - see front matter  2012 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved. doi:10.1016/j.humimm.2012.02.020