Background: In search of an alternative screening technique, we compared complement-dependent cytotoxicity (CDC) with PRA-STAT, a commercially available enzyme-linked immunosorbent assay (ELISA).
Methods: A total of 188 pre- and posttransplant sera from 50 renal allograft recipients were tested with both methods.
Results: A significant correlation was found between both methods. Discrepant results could be explained by the fact that PRA-STAT detects both HLA class I and II antibodies (while CDC with peripheral blood lymphocytes as target cell detects mainly HLA class I reactivity), by the presence of IgM antibodies (which are not detected by the IgG-specific ELISA test), and by CDC "false-positive" results due to antibody rejection treatment. The clinical relevance of antibodies detected by PRA-STAT is suggested by the following. (a) In eight patients, donor-specific HLA antibodies detected by PRA-STAT (but not seen by CDC) resulted in severe rejection episodes, which led to graft loss in four cases. In all but one patient, antibodies were directed against class II or mixtures of class I and H antigens. Six patients with complications were shown to have developed de novo antibodies against DQ incompatibilities. (b) Half of the patients with a positive ELISA test at the moment of crossmatch experienced complications. Such patients are at a threefold higher risk of suffering from rejection episodes and/or graft loss than patients who are not sensitized (P<0.05, Fisher exact test).
Conclusions: Because PRA-STAT is very reproducible, detects both HLA class I and II antibodies, and is not influenced by rejection therapy, we consider it an additional tool for pre- and posttransplant monitoring of kidney allograft recipients.
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http://dx.doi.org/10.1097/00007890-199806150-00024 | DOI Listing |
HLA
January 2025
Department of Clinical Hematology and Medical Oncology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Novel MICB alleles MICB*004:01:31, MICB*004:01:32, MICB*004:01:33 and MICB*005:02:59, were identified using next generation sequencing.
View Article and Find Full Text PDFJID Innov
March 2025
Department of Dermatology, University Hospital of Zurich, University of Zurich, Schlieren, Switzerland.
In cutaneous melanoma, epigenetic dysregulation is implicated in drug resistance and tumor immune escape. However, the epigenetic mechanisms that influence immune escape remain poorly understood. To elucidate how epigenetic dysregulation alters the expression of surface proteins that may be involved in drug targeting and immune escape, we performed a 3-dimensional surfaceome screen in primary melanoma cultures and identified the DNA-methyltransferase inhibitor decitabine as significantly upregulating the costimulatory molecule ICAM-1.
View Article and Find Full Text PDFImmunohorizons
January 2025
Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, United States.
Antibody (Ab) crosslinking of HLA class II (HLA II) molecules on the surface of endothelial cells (ECs) triggers proliferative and prosurvival intracellular signaling, which are implicated in promoting chronic Ab-mediated rejection (cAMR). Despite the importance of cAMR in transplant medicine, the mechanisms involved remain incompletely understood. Here, we examined the regulation of yes-associated protein (YAP) nuclear cytoplasmic localization and phosphorylation in human ECs challenged with Abs that bind HLA II, which are strongly associated with cAMR.
View Article and Find Full Text PDFInt J Immunogenet
January 2025
Department of Clinical Haematology and Medical Oncology, Postgraduate Institute of Medical Education & Research, Chandigarh, India.
High degree of variability in human leukocyte antigens (HLAs) system restricts availability of histocompatible HLA-matched-related donors, thus increasing reliance on worldwide bone marrow registries network. Nevertheless, due to limited coverage/accessibility/affordability of some ethnicities in these registries, haploidentical haematopoietic stem cell transplantation (HSCT) emerged as an alternative option, though with allorecognition-mediated graft versus host disease (GvHD) (>40% cases). A dimorphism [-21 methionine (M) or threonine (T)] in HLA-B leader peptide (exon 1) which differentially influences its HLA-E binding, plausibly regulates natural killer cell functionality, affecting GvHD vulnerability and clinically in practice for donor selection.
View Article and Find Full Text PDFHLA
January 2025
Servicio de Inmunología, Instituto de Biomedicina de Sevilla, IBiS/Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.
Description of two novel HLA class II alleles, DPB1*1626:01Q and DRB1*11:337 alleles.
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