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Multicenter Study
. 2022 May;28(5):989-998.
doi: 10.1038/s41591-022-01725-2. Epub 2022 Mar 14.

The MHC class I MICA gene is a histocompatibility antigen in kidney transplantation

Raphael Carapito  1   2   3   4   5 , Ismail Aouadi  6   7   8   9 , Martin Verniquet  6   7   8   9 , Meiggie Untrau  6   7   8   9 , Angélique Pichot  6   7   8   9 , Thomas Beaudrey  6   7   9   10 , Xavier Bassand  6   7   9   10 , Sébastien Meyer  6   7   8   9 , Loic Faucher  7   11 , Juliane Posson  12   13 , Aurore Morlon  7   14 , Irina Kotova  7   14 , Florent Delbos  7   15 , Alexandre Walencik  7   15 , Alice Aarnink  16 , Anne Kennel  16 , Caroline Suberbielle  7   17 , Jean-Luc Taupin  7   17 , Benedict M Matern  18 , Eric Spierings  18 , Nicolas Congy-Jolivet  7   19   20 , Arnaud Essaydi  21 , Peggy Perrin  6   7   9   10 , Antoine Blancher  7   19   20 , Dominique Charron  7   9   17 , Nezih Cereb  22 , Myriam Maumy-Bertrand  7   9   23 , Frédéric Bertrand  7   9   23 , Valérie Garrigue  7   24 , Vincent Pernin  7   24 , Laurent Weekers  25 , Maarten Naesens  26 , Nassim Kamar  7   27 , Christophe Legendre  7   28 , Denis Glotz  7   12   13 , Sophie Caillard  6   7   9   10 , Marc Ladrière  29 , Magali Giral  7   11 , Dany Anglicheau  7   28   30 , Caner Süsal  31   32 , Seiamak Bahram  33   34   35   36   37
Affiliations
Multicenter Study

The MHC class I MICA gene is a histocompatibility antigen in kidney transplantation

Raphael Carapito et al. Nat Med. 2022 May.

Abstract

The identity of histocompatibility loci, besides human leukocyte antigen (HLA), remains elusive. The major histocompatibility complex (MHC) class I MICA gene is a candidate histocompatibility locus. Here, we investigate its role in a French multicenter cohort of 1,356 kidney transplants. MICA mismatches were associated with decreased graft survival (hazard ratio (HR), 2.12; 95% confidence interval (CI): 1.45-3.11; P < 0.001). Both before and after transplantation anti-MICA donor-specific antibodies (DSA) were strongly associated with increased antibody-mediated rejection (ABMR) (HR, 3.79; 95% CI: 1.94-7.39; P < 0.001; HR, 9.92; 95% CI: 7.43-13.20; P < 0.001, respectively). This effect was synergetic with that of anti-HLA DSA before and after transplantation (HR, 25.68; 95% CI: 3.31-199.41; P = 0.002; HR, 82.67; 95% CI: 33.67-202.97; P < 0.001, respectively). De novo-developed anti-MICA DSA were the most harmful because they were also associated with reduced graft survival (HR, 1.29; 95% CI: 1.05-1.58; P = 0.014). Finally, the damaging effect of anti-MICA DSA on graft survival was confirmed in an independent cohort of 168 patients with ABMR (HR, 1.71; 95% CI: 1.02-2.86; P = 0.041). In conclusion, assessment of MICA matching and immunization for the identification of patients at high risk for transplant rejection and loss is warranted.

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Conflict of interest statement

D.A. has a patent ‘In vitro method for determining the likelihood of occurrence of an acute microvascular rejection (AMVR) against a renal allograft in an individual’ (EP19305037.4) issued. S.B. reports grants and personal fees from BIOMICA and personal fees from GenDx. S.C. reports non-financial support from Sanofi and Astellas, and non-financial support from Novartis, outside the submitted work. N.K. reports personal fees from Abbvie, Amgen, Astellas, Biotest, CSL Behring, Chiesi, Gilead, Fresenius Medical care, Merck Sharp and Dohme, Neovii, Novartis Pharma, Sanofi, Sandoz and Shire, outside the submitted work. P.P. reports personal fees from Chiesi, outside the submitted work. All other authors have no competing interests.

Figures

Fig. 1
Fig. 1. Kaplan–Meier curves for kidney graft survival according to MICA matching status.
The probability of graft survival is shown for matched versus mismatched patients using the presence or absence of mismatches at the MICA locus (a) or the number of mismatches (b) as classification criteria. P values were determined using the two-sided log-rank test without correction. Source data
Fig. 2
Fig. 2. Cumulative incidence of antibody-mediated rejection according to anti-MICA DSA status.
The cumulative incidence of antibody-mediated rejection is shown for patients with versus those without preformed anti-MICA DSA (a) and for patients with versus those without anti-MICA DSA 1 year after transplantation (b). P values were determined using the two-sided log-rank test without correction. Source data
Fig. 3
Fig. 3. Cumulative incidence of antibody-mediated rejection according to anti-MICA and anti-HLA DSA status.
The cumulative incidence of antibody-mediated rejection is shown for patients without DSA, with anti-MICA or anti-HLA DSA, and with both anti-MICA and anti-HLA DSA. The analysis was carried out for preformed (a) and post-transplantation DSA (b). P values were determined using the two-sided log-rank test without correction. Exact P values: a, P = 1.44 × 10−10; b, P = 5.03 × 10−17. Source data
Extended Data Fig. 1
Extended Data Fig. 1. Kaplan–Meier curves for kidney graft survival according to the MICA matching status in HLA-B matched patients as determined by high-resolution HLA-typing.
The probability of graft survival is shown for patients matched versus mismatched at the MICA locus using presence/absence of mismatches. Two-sided log-rank test p-value without correction is shown. Source data
Extended Data Fig. 2
Extended Data Fig. 2. Kaplan–Meier curves for kidney graft survival according to anti-MICA and anti-HLA DSA antibodies in an independent cohort with ABMR.
The probability of graft survival is shown for patients with anti-MICA DSA at the time of biopsy versus those without anti-MICA DSA (panel A) and for patients without DSA, with anti-MICA or anti-HLA DSA, and with both anti-MICA and anti-HLA DSA (panel B). Two-sided log-rank test P values without correction are shown. Source data
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Comment in

  • MICA in kidney transplants.
    Allison SJ. Allison SJ. Nat Rev Nephrol. 2022 May;18(5):273. doi: 10.1038/s41581-022-00563-2. Nat Rev Nephrol. 2022. PMID: 35338343 No abstract available.

References

    1. Knechtle, S., Marson, L. & Morris, P. Kidney Transplantation – Principles and Practice (Elsevier, 2019).
    1. Merrill JP, Murray JE, Harrison JH, Guild WR. Successful homotransplantation of the human kidney between identical twins. JAMA. 1956;160:277–282. doi: 10.1001/jama.1956.02960390027008. - DOI - PubMed
    1. Snell GD. Methods for the study of histocompatibility genes. J. Genet. 1948;49:87–108. doi: 10.1007/BF02986826. - DOI - PubMed
    1. Snell GD. Studies in histocompatibility. Science. 1981;213:172–178. doi: 10.1126/science.7017931. - DOI - PubMed
    1. Bohmig GA, Eskandary F, Doberer K, Halloran PF. The therapeutic challenge of late antibody-mediated kidney allograft rejection. Transpl. Int. 2019;32:775–788. doi: 10.1111/tri.13436. - DOI - PMC - PubMed

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