Association of Kidney Transplant Failure and Antibodies Against MICA

Mizutani, Kazuo; Terasaki, Paul I.; Bignon, J.; Hourmant, Maryvonne; Cesbron‐Gautier, Anne; Shih, Remi; Pei, Rui; Lee, Jar-How; Ozawa, Miyuki

doi:10.1016/j.humimm.2006.06.002

Cited by 71 publications

(36 citation statements)

References 20 publications

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“…Renal and pancreatic grafts in patients with evidence of both acute and chronic rejection have been shown to express MICA/B proteins and anti-MICA/B antibodies are present in the serum of these patients [109]. The presence of sMICA has also been correlated with a lower incidence of graft rejection [110].…”

Section: Nkg2d In Grafts and Transplantationmentioning

confidence: 99%

The NKG2D receptor: immunobiology and clinical implications

et al. 2007

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NK cells are critical components of our immune system functioning, in part, to recognize and then eradicate virally infected or tumorigenic cells without previous sensitization. One of the best-characterized activating receptors expressed on NK cells is the NKG2D receptor, which is capable of transmitting co-stimulatory signals by subsets of T cells. Viruses and tumors have evolved strategies to evade NKG2D-mediated immune recognition thus highlighting the importance of this receptor in immunity. This review will focus on the structure of NKG2D and its interaction with its diverse array of ligands, as well as highlighting current knowledge regarding NKG2D signal transduction and biological mechanisms that govern its cell surface expression. The impact that NKG2D has in disease pathologies is also assessed.

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Section: Nkg2d In Grafts and Transplantationmentioning

confidence: 99%

The NKG2D receptor: immunobiology and clinical implications

et al. 2007

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“…Initial studies reported on specific antibodies against MICA in the serum of patients who had rejected kidney allografts, suggesting a role for these molecules in transplant immunopathology. 14,15 Expression of MICA in transplanted organs has been demonstrated, and anti-MICA antibodies have been associated with both acute and chronic rejection in renal, 16,17 pancreatic, 18 and heart transplants. 19 In renal transplantation, anti-MICA antibodies after transplantation have been reported in 5%-9% of recipients and cause a 10% decrease in graft survival at 1 year.…”

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confidence: 99%

MICA Variant Promotes Allosensitization after Kidney Transplantation

Tonnerre

Gérard

Chatelais

et al. 2013

Journal of the American Society of Nephrology

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MHC class I-related chain A (MICA) antigens are surface glycoproteins strongly implicated in innate immunity, and the MICA gene is highly polymorphic. Clinical observations suggest a role for donor MICA antigens expressed on transplant endothelial cells in the alloimmune response, but the effect of MICA genotype is not well understood. Here, we investigated the immunologic effect of the A5.1 mutation, related to the common MICA*008 allele. Compared with wild-type endothelial cells (ECs), homozygosity for MICA A5.1 associated with an endothelial phenotype characterized by 7-to 10-fold higher levels of MICA mRNA and MICA proteins at the cell surface, as well as exclusive release in exosomes instead of enzymatic cleavage. Mechanistically, we did not detect quantitative changes in regulatory microRNAs. Functionally, A5.1 ECs enhanced NKG2D interaction and natural killer cell activation, promoting NKG2D-dependent lysis of ECs. In kidney transplant recipients, polyreactive anti-MICA sera bound preferentially to ECs from MICA A5.1 donors, suggesting that MICA*008(A5.1) molecules are the preferential antigenic determinants on ECs of grafts. Furthermore, the incidence of MICA A5.1 mismatch revealed a statistically significant association between donor MICA A5.1 and both anti-MICA sensitization and increased proteinuria in kidney recipients. Taken together, these results identify the A5.1 mutation as an immunodominant factor and a potential risk factor for transplant survival.

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“…Mizutani et al [1] reported association of all these antibodies independently with slow graft failure. However, the most important of these are IgG anti HLA class I antibodies.…”

Section: Discussionmentioning

confidence: 99%

“…[1][2][3] Of these, the antibodies against HLA class I antigens are probably the most important and are most frequently monitored. Panel reactive antibodies (PRA) and cross match (XM) are the tests used for detection of HLA class I antibodies.…”

Section: Introductionmentioning

confidence: 99%

Highly Successful and Low-Cost Desensitization Regime for Sensitized Living Donor Renal Transplant Recipients

et al. 2009

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10-30% of dialysis population awaiting renal transplantation is sensitized. Present desensitization protocols use intravenous immune globulins, rituximab, and plasmapheresis in various combinations; however, these regimens are unaffordable by many in developing countries. We tried desensitization with mycophenolate mofetil and plasmapheresis. Methods. Patients with high PRA titre (>50%) or positive crossmatch (>10%) were treated with MMF for a month before proposed transplant and were given five sittings of plasmapheresis. Results. 11 of 12 patients had normalization of PRA/crossmatch with this regimen and were successfully transplanted. One patient lost the graft due to graft vein thrombosis, and two patients died within three months after transplant due to septicemia and pulmonary embolism, respectively, with a functioning graft. No patient, including the two who died, developed clinical rejection over a mean follow-up of 10 months (range 1-16 months). Mean serum creatinine at last follow up was 1.1 mg/dL (range 0.9-1.3 mg/dL). Conclusions. Though the number of patients studied is small, we feel that highly sensitized patients awaiting living donor renal transplant should be tried on this simple and cost-effective regime before transplant. The more aggressive and expensive approaches incorporating IVIg and rituximab should be used only if this relatively low-cost regime is unsuccessful.

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Association of Kidney Transplant Failure and Antibodies Against MICA

Cited by 71 publications

References 20 publications

The NKG2D receptor: immunobiology and clinical implications

The NKG2D receptor: immunobiology and clinical implications

MICA Variant Promotes Allosensitization after Kidney Transplantation

Highly Successful and Low-Cost Desensitization Regime for Sensitized Living Donor Renal Transplant Recipients

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