Role of MICA in the immune response to transplants

ArticleinTissue Antigens 76(3):171-6 · September 2010with4 Reads
DOI: 10.1111/j.1399-0039.2010.01527.x · Source: PubMed
Among the cell surface antigens that can elicit an immune response in transplant recipients MICA antigens occupy a special place. They are similar to human leukocyte antigens (HLAs) while being very different from them. They are not as polymorphic and their quantity is smaller. In consequence, the impact of MICA antigens in transplantation is not as dramatic. However, our early guess that these ligands of NKG2D could elicit antibodies and cell-mediated immunity has been definitely confirmed. Careful analysis with MICA transfectant cells, for absorption and elution, established the specificity of the epitopes involved. Typing of recipients and donors by sequencing the MICA alleles has established that de novo antibodies produced in kidney transplant recipients are directed at mismatched MICA epitopes and are associated with acute rejection and chronic transplant failure. Acute graft-versus-host disease was observed in stem cell recipients who were mismatched for MICA.
    • "The presence of MICA antibody was detected in 217 patients in a large cohort of 1910 renal transplant recipients (11.4%) and was associated with renal allograft rejection and poor allograft survival at one year after transplantation (83.2 ± 5.8% compared to 95.1 ± 1.3% in RTR with good HLA matching, p = 0.002) [33]. Typing of recipients and donors by sequencing their MICA alleles also suggested that the de novo antibodies produced in kidney transplant recipients are directed at mismatched MICA epitopes and are associated with acute rejection and chronic transplant failure [34]. Despite these association studies, confirmation that MICA antibodies have a deleterious impact on graft outcome independent of HLA DSAs remains lacking. "
    [Show abstract] [Hide abstract] ABSTRACT: Antibody-mediated rejection (ABMR) is associated with poor transplant outcome. Pathogenic alloantibodies are usually directed against human leukocyte antigens (HLAs). Histological findings suggestive of ABMR usually demonstrate an anti-HLA donor-specific antibody (DSA)-mediated injury, while a small subset of patients develops acute dysfunction with histological lesions suggestive of ABMR in the absence of anti-HLA DSAs. Although this non-HLA ABMR is not well recognized by current diagnostic classifications, it is associated with graft dysfunction and allograft loss. These clinical descriptions suggest a pathogenic role for non-HLA anti-endothelial cell antibodies. Diverse antigenic targets have been described during the last decade. This review discusses recent findings in the field and addresses the clinical relevance of anti-endothelial cell antibodies (AECAs).
    Article · May 2016
    • "A further modifying factor is sMICA (Boukouaci et al, 2009), which was found in variable amounts in patient sera (Salih et al, 2002; Boissel et al, 2006; Nü ckel et al, 2010; Hilpert et al, 2012). Moreover, anti-MICA Ab (Boukouaci et al, 2009), neutralizing sMICA but also sensitizing MICA-expressing cells to complement-dependent cellular cytotoxicity (Zou et al, 2002; Jinushi et al, 2006; Zou & Stastny, 2010), might additionally modulate the effects of the SNP MICA-129. In conclusion, we have shown that the MICA-129Val/Met dimorphism affects the strength and kinetics of NKG2D signaling resulting in differences of NK-cell cytotoxicity and cytokine secretion as well as CD8 + T-cell co-stimulation. "
    [Show abstract] [Hide abstract] ABSTRACT: The MHC class I chain-related molecule A (MICA) is a highly polymorphic ligand for the activating natural killer (NK)-cell receptor NKG2D. A single nucleotide polymorphism causes a valine to methionine exchange at position 129. Presence of a MICA-129Met allele in patients (n = 452) undergoing hematopoietic stem cell transplantation (HSCT) increased the chance of overall survival (hazard ratio [HR] = 0.77, P = 0.0445) and reduced the risk to die due to acute graft-versus-host disease (aGVHD) (odds ratio [OR] = 0.57, P = 0.0400) although homozygous carriers had an increased risk to experience this complication (OR = 1.92, P = 0.0371). Overall survival of MICA-129Val/Val genotype carriers was improved when treated with anti-thymocyte globulin (HR = 0.54, P = 0.0166). Functionally, the MICA-129Met isoform was characterized by stronger NKG2D signaling, triggering more NK-cell cytotoxicity and interferon-γ release, and faster co-stimulation of CD8(+) T cells. The MICA-129Met variant also induced a faster and stronger down-regulation of NKG2D on NK and CD8(+) T cells than the MICA-129Val isoform. The reduced cell surface expression of NKG2D in response to engagement by MICA-129Met variants appeared to reduce the severity of aGVHD.
    Full-text · Article · Oct 2015
    • "These antigens are recognized by NKG2D, an activating receptor for cytotoxic natural killer (NK) and CD8 + T cells [13,14]. Therefore, MICA is capable of stimulating cellular immunity against transplanted grafts and/or able to trigger graft-versushost reaction against mismatched MICA antigens possessed by donors and recipients [15] . In contrast, KIRs are not markers of tissue identity, but they do mediate self-recognition by NK cells through their interaction with HLA class I ligands. "
    [Show abstract] [Hide abstract] ABSTRACT: Transplantation and transfusion are related and clinically important areas of multidisciplinary expertise, including pre-operative treatment, donor recruitment, tissue matching, and post-operative care. We have seen significant developments in these areas, especially in the late 20th and early 21st century. This paper reviews the latest advances in modern transplantation and transfusion medicine, including several new genetic markers (e.g., major histocompatibility complex class I chain-related gene A, killer cell immunoglobulin-like receptor, and human platelet antigens) for donor and recipient matching, genotyping platforms (e.g., next-generation sequencer and Luminex technology), donor recruitment strategies, and several clinical applications in which genotyping has advantages over agglutination tests (e.g., genotyping of weakly expressed antigens and determination of blood groups and human leukocyte antigen types in multi-transfused patients). We also highlight the roles of population studies and international collaborations in moving towards more efficient donor recruitment strategies.
    Full-text · Article · Jul 2015
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