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Cecka J.M.,University of California at Los Angeles | Kucheryavaya A.Y.,United Network for Organ Sharing | Reinsmoen N.L.,Cedars Sinai Comprehensive Transplant Center | Leffell M.S.,Immunogenetics Laboratory
American Journal of Transplantation | Year: 2011

The calculated panel reactive antibody (CPRA), which is based upon unacceptable HLA antigens listed on the waitlist form for renal transplant candidates, replaced PRA as the measure of sensitization among US renal transplant candidates on October 1, 2009. An analysis of the impact of this change 6 months after its implementation shows an 83% reduction in the number of kidney offers declined nationwide because of a positive crossmatch. The increasing acceptance and utilization of unacceptable HLA antigens to avoid offers of predictably crossmatch-positive donor kidneys has increased the efficiency of kidney allocation, resulting in a significant increase in the percentage of transplants to broadly sensitized (80+% PRA/CPRA) patients from 7.3% during the period 07/01/2001-6/30/2002 to 15.8% of transplants between 10/1/09-3/31/10. The transplant rates per 1000 active patient-years on the waitlist also increased significantly for broadly sensitized patients after October 1, 2009. These preliminary results suggest that 'virtual' positive crossmatch prediction based on contemporary tools for identifying antibodies directed against HLA antigens is effective, increases allocation efficiency and improves access to transplants for sensitized patients awaiting kidney transplantation. © 2010 The Authors.

Jackson A.M.,Immunogenetics Laboratory | Melancon J.K.,Georgetown University
Transplantation | Year: 2011

Background: ABO and human leukocyte antigen (HLA) alloantibodies provide major immunologic barriers to successful transplantation; however, there is increasing recognition for the role of anti-endothelial cell antibodies (AECAs) in allograft rejection. We investigated the relationship between AECAs identified using donor-derived endothelial cell precursors (ECPs) and kidney allograft rejection and function. Methods: Sixty live donor kidney recipients were tested pretransplant for AECAs and HLA-antibodies using flow cytometric crossmatch tests and solid-phase bead immunoassays. Renal allograft function was assessed by serum creatinine (SCr) values collected at early (mean, 50 days) and late (mean, 815 days) time points posttransplant and by incidence and type of rejection. Immunoglobulin G (IgG) subtype determination of both AECAs and HLA antibodies bound to ECPs was performed using flow cytometry. Results: Fourteen patients (23%) tested positive for donor-reactive IgG AECAs and had statistically higher SCr values and incidences of cellular rejection early posttransplant compared with 46 patients who tested negative (P=0.014 and P<0.05). SCr values were not statistically different late posttransplant. IgG subclass determination showed AECAs to be enriched for IgG2 and IgG4, subclasses that do not activate complement effectively. Detection of donor-reactive immunoglobulin M (IgM) AECAs did not correlate with increased SCr or incidence of rejection. CONCLUSION.: Crossmatch tests performed using donor-derived ECPs allow for the identification of alloantibodies that are associated with cellular rejection and are distinct from alloantibodies detected using lymphocytes. © 2011 by Lippincott Williams & Wilkins.

Anagnostouli M.,National and Kapodistrian University of Athens | Anagnostouli M.,Immunogenetics Laboratory | Anagnostoulis G.,Intensive Care Unit | Katsavos S.,National and Kapodistrian University of Athens | And 4 more authors.
Journal of the Neurological Sciences | Year: 2014

Background Multiple sclerosis (MS) patients have a low general cancer risk and cases of neoplastic comorbidity are attributed by many researchers in chance, or therapeutical side-effects. Human leucocyte antigen (HLA) class II allele DRB1*15:01 is considered the main genetic factor independently associated with increased susceptibility for MS in Caucasians. Epstein-Barr virus (EBV) has also been proven to be a core triggering factor in MS initiation and progress, mainly in HLA-DRB1*15:01 positive MS patients. Case report We present an exceptional case of a Greek-origin woman, carrying a distinct immunogenetic profile (HLA-A*26:01-Cw*06:02-DRB1*15:01), which gradually developed psoriasis, nasopharyngeal carcinoma (NPC), MS, breast cancer, uterine leiomyoma and other neoplasms. Discussion EBV plays a fundamental role in the pathogenesis of both autoimmunity (i.e. MS) and cancer (i.e. NPC). Our patient's immunogenetic profile included HLA alleles which are associated with psoriasis (Cw*06:02), NPC (A*26:01), MS (DRB1*15:01) and increased risk of MS, in patients carrying EBV (DRB1*15:01). We made a targeted review of the literature finding data supporting an EBV-HLA interaction mechanism behind our patient's unique combination of disorders, suggesting that beyond the standard role of each factor, their combination could act as the hidden link, in initiation or/and comorbidity of autoimmunity and cancer. © 2014 Elsevier B.V.

Fainboim L.,Immunogenetics Laboratory | Fainboim L.,CONICET | Fainboim L.,University of Buenos Aires | Arruvito L.,Immunogenetics Laboratory | And 2 more authors.
Journal of Reproductive Immunology | Year: 2011

Several studies have reported that the fine-tuning of regulatory T cells (Tregs) is required for a successful pregnancy and for the control of autoimmune diseases. Here, we review the mechanisms that control the expansion of Tregs, based on insights obtained from the study of women suffering unsuccessful pregnancies and on recent data from patients with autoimmune diseases or with chronic viral infections such as HCV. In particular, we review the role of endocrine factors and IL-2/STAT5 signalling in the impaired expansion of Tregs. © 2011 Elsevier Ireland Ltd.

Di Cristofaro J.,Aix - Marseille University | Frassati C.,Immunogenetics Laboratory | Montagnie R.,Immunogenetics Laboratory | Basire A.,Immunogenetics Laboratory | And 3 more authors.
Platelets | Year: 2015

Fetal/neonatal allo-immune thrombocytopenia is the most frequent and the most dangerous clinical condition involving anti-human platelet antigens (HPA)-1a allo-antibodies. Anti-HPA-1a allo-immunization requires rapid and accurate diagnosis to determine appropriate treatment. The Capture-P Ready-Screen assay (C-PRS) is a new qualitative immunoassay to detect IgG anti-human leukocyte antigen (HLA) and anti-HPA allo-antibodies. The aim of this study is to assess the identification of anti-HPA-1a allo-antibodies using the C-PRS assay, associated with HLA class I stripping reagents, on the automated benchtop analyzer Galileo Echo. Forty-nine sera were analyzed: without anti-HLA class I or anti-HPA allo-antibodies, with anti-HLA class I allo-antibodies, with anti-HPA-1a allo-antibodies, among which with anti-HLA class I allo-antibodies. None of the samples without allo-antibodies were reactive. Only anti-HLA antibodies, detected by cytotoxicity-dependent complement and not by Luminex, remained positive before and after stripping reagents. Of the 13 samples, anti-HPA-1a allo-antibodies that were correctly identified before and after incubation with HLA assassin reagent were 70% and 85%, respectively. Anti-glycoprotein auto-antibodies and anti-HLA allo-antibodies do not interfere with the detection of anti-HPA-1a antibodies. This preliminary study indicates that further improvement of the test will be helpful in developing a clinically useful assay in the future. © 2014 Informa UK Ltd. All rights reserved.

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