TRANSPLANTATION

Histocompatibility: minor differences have a major impact

The clinical relevance of minor histocompatibility antigens in transplantation is disputed. High-throughput approaches are now being used to investigate the role of genome-wide genetic incompatibility in transplant outcomes. A recent study reports that donor and recipient mismatch at the LIMS1 locus is associated with an increased risk of acute rejection.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Fig. 1: Hypothetical mechanisms by which the LIMS1 collision genotype might lead to acute cellular rejection.

References

  1. 1.

    Opelz, G. & Collaborative Transplant Study. Non-HLA transplantation immunity revealed by lymphocytotoxic antibodies. Lancet 365, 1570–1576 (2005).

  2. 2.

    Steers, N. J. et al. Genomic mismatch at LIMS1 locus and kidney allograft rejection. N. Engl. J. Med. 380, 1918–1928 (2019).

  3. 3.

    Reindl-Schwaighofer, R. et al. Mechanisms underlying human genetic diversity: consequence for antigraft antibody responses. Transpl. Int. 31, 239–250 (2018).

  4. 4.

    Xu, H., Cao, H. & Xiao, G. Signaling via PINCH: functions, binding partners and implications in human diseases. Gene 594, 10–15 (2016).

  5. 5.

    Yang, Y. et al. Formation and phosphorylation of the PINCH-1-integrin linked kinase-alpha-parvin complex are important for regulation of renal glomerular podocyte adhesion, architecture, and survival. J. Am. Soc. Nephrol. 16, 1966–1976 (2005).

  6. 6.

    Li, Y. et al. PINCH-1 promotes tubular epithelial-to-mesenchymal transition by interacting with integrin-linked kinase. J. Am. Soc. Nephrol. 18, 2534–2543 (2007).

  7. 7.

    Scanlan, M. J. et al. Antigens recognized by autologous antibody in patients with renal-cell carcinoma. Int. J. Cancer 83, 456–464 (1999).

  8. 8.

    Reindl-Schwaighofer, R. et al. Contribution of non-HLA incompatibility between donor and recipient to kidney allograft survival: genome-wide analysis in a prospective cohort. Lancet 393, 910–917 (2019).

  9. 9.

    Delville, M. et al. Early acute microvascular kidney transplant rejection in the absence of anti-HLA antibodies is associated with preformed IgG antibodies against diverse glomerular endothelial cell antigens. J. Am. Soc. Nephrol. 30, 692–709 (2019).

  10. 10.

    Wiebe, C. et al. Class II HLA epitope matching-A strategy to minimize de novo donor-specific antibody development and improve outcomes. Am. J. Transplant. 13, 3114–3122 (2013).

Download references

Acknowledgements

We acknowledge the generous help of A. Heinzel (Medical University of Vienna, Austria) in preparing this article. This work was supported by the Vienna Science and Technology Fund WWTF (grant # LS16-019 and # LS18-031) and the Österreichisch Nationalbank (grant # 17289).

Author information

Affiliations

Authors

Corresponding author

Correspondence to Rainer Oberbauer.

Ethics declarations

Competing interests

The authors declare no competing interests.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Reindl-Schwaighofer, R., Oberbauer, R. Histocompatibility: minor differences have a major impact. Nat Rev Nephrol 15, 529–530 (2019). https://doi.org/10.1038/s41581-019-0175-y

Download citation