Identification of the nonclassical HLA molecules, mica, as targets for humoral immunity associated with irreversible rejection of kidney allografts1

Sumitran–Holgersson, Suchitra; Wilczek, H. E.; Holgersson, Jan; Söderström, Kalle

doi:10.1097/00007890-200207270-00019

Cited by 188 publications

(134 citation statements)

References 23 publications

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“…9 Some of these polymorphisms modulate binding affinities with NKG2D. 10 Recent studies 11,12 suggest that MICA might be an additional histocompatibility locus.…”

Section: Introductionmentioning

confidence: 99%

MICA, HLA-B haplotypic variation in five population groups of sub-Saharan African ancestry

Tian

et al. 2003

Genes Immun

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The human major histocompatibility complex (MHC) class I chain-related gene A (MICA), located 46 kb centromeric to HLA-B, encodes a stress-inducible protein, which is a ligand for the NKG2D receptor. In addition to its primary role in immune surveillance, data suggest that MICA is involved in the immune response to transplants and in susceptibility to some diseases. In this study, 152 subjects from the Yoruba (n¼74), Efik (n¼32), and Igbo (n¼46) tribes of southern Nigeria, 39 nationwide African-American stem cell donors, and 60 African-American individuals residing in the metropolitan Boston area were studied for MICA, HLA-B allelic variation, haplotypic diversity, and linkage disequilibrium (LD). MICA and HLA-B exhibited a high degree of genetic diversity among the populations studied. In particular, MICA allele and HLA-B-MICA haplotype frequencies and LD in the Efik and Igbo tribes were significantly different from the other study groups. HLA-B and MICA loci demonstrated significant global LD in all five populations (P-values o0.00001). LD also varied in a haplotype-specific manner. A novel MICA allele was detected in the Boston population. These findings are important from an anthropologic perspective, and will inform future HLA-linked disease association studies in related ethnic groups of African-derived ancestry.

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“…9 Some of these polymorphisms modulate binding affinities with NKG2D. 10 Recent studies 11,12 suggest that MICA might be an additional histocompatibility locus.…”

Section: Introductionmentioning

confidence: 99%

MICA, HLA-B haplotypic variation in five population groups of sub-Saharan African ancestry

Tian

et al. 2003

Genes Immun

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“…8 Despite improved understanding of the assessment and monitoring for HLA mismatched epitopes, 8 the pathogenicity of donor-specific anti-HLA antibodies on CAI remains elusive. 9 This is shown with complete HLA matched transplants exhibiting finite survival due to progressive CAI, 10 and not infrequently, CAI observed in HLA mismatched grafts without demonstrable antibodies to donor-specific HLA antigens. 7 These findings strongly suggest that additional pathogenic antibodies drive the humoral axis of injury in CAI, 9,11 and may be the final common outcome.…”

mentioning

confidence: 98%

Non-HLA Antibodies to Immunogenic Epitopes Predict the Evolution of Chronic Renal Allograft Injury

Sigdel

Li²,

Tran³

et al. 2012

Journal of the American Society of Nephrology

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Chronic allograft injury (CAI) results from a humoral response to mismatches in immunogenic epitopes between the donor and recipient. Although alloantibodies against HLA antigens contribute to the pathogenesis of CAI, alloantibodies against non-HLA antigens likely contribute as well. Here, we used highdensity protein arrays to identify non-HLA antibodies in CAI and subsequently validated a subset in a cohort of 172 serum samples collected serially post-transplantation. There were 38 de novo non-HLA antibodies that significantly associated with the development of CAI (P,0.01) on protocol post-transplant biopsies, with enrichment of their corresponding antigens in the renal cortex. Baseline levels of preformed antibodies to MIG (also called CXCL9), ITAC (also called CXCL11), IFN-g, and glial-derived neurotrophic factor positively correlated with histologic injury at 24 months. Measuring levels of these four antibodies could help clinicians predict the development of CAI with .80% sensitivity and 100% specificity. In conclusion, pretransplant serum levels of a defined panel of alloantibodies targeting non-HLA immunogenic antigens associate with histologic CAI in the post-transplant period. Validation in a larger, prospective transplant cohort may lead to a noninvasive method to predict and monitor for CAI.

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“…In addition to HLA, several studies have shown that autoantibodies and antibodies to minor histocompatibility antigens may be associated with acute or chronic renal allograft rejection and graft loss. [12][13][14][15][16] Consequently, in the era of advanced immunosuppressive therapy, HLA matching of only 3 loci may have less signifi cance on survival of livingunrelated grafts. Although, in our results, graft outcomes from spousal donors were comparable to those from other LUDs, the results may have been affected by the use of MMF.…”

Section: Discussionmentioning

confidence: 99%

Renal Allograft Outcomes From Spousal and Other Living‐Unrelated Donors

Lee

Kim

et al. 2009

Dialysis & Transplantation

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OBJECTIVEThe objective of this study was to compare renal allograft outcomes from spousal donors with those from other living‐unrelated donors (LUD), and to make the best use of spousal donors.METHODSFrom February 1995 to February 2006, 812 renal transplantations were performed at our center, of which 185 were from LUDs. A retrospective analysis was made of all recipients who successfully underwent living‐unrelated renal transplantation.RESULTSA total of 55 out of the 185 recipients received a kidney from their spouses. Compared with other LUDs, spousal donors were older and had poorer human leukocyte antigen (HLA) mismatching. The time from initiation of dialysis to transplantation was shorter in transplantation from spousal donors. The incidence of acute rejection within the first year after transplantation was more frequent in spousal grafts. However 1‐year and 5‐year survival rates for spousal and other living‐unrelated grafts were not significantly different (96.3% and 93.7% for spousal grafts versus 97.7% and 89.3% for other living‐unrelated grafts, p = .925). The survival rate for 5‐year patients was 96.4% and 97.5%, respectively.DISCUSSIONTransplantation from spousal donors has comparable outcomes to those of other LUDs, and shortens time spent on the waiting list. Therefore, spousal donation should be considered as a useful source to overcome an organ shortage.

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Identification of the nonclassical HLA molecules, mica, as targets for humoral immunity associated with irreversible rejection of kidney allografts1

Cited by 188 publications

References 23 publications

MICA, HLA-B haplotypic variation in five population groups of sub-Saharan African ancestry

MICA, HLA-B haplotypic variation in five population groups of sub-Saharan African ancestry

Non-HLA Antibodies to Immunogenic Epitopes Predict the Evolution of Chronic Renal Allograft Injury

Renal Allograft Outcomes From Spousal and Other Living‐Unrelated Donors

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