Research ArticleAutoimmunity

Transglutaminase 4 as a prostate autoantigen in male subfertility

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Science Translational Medicine  17 Jun 2015:
Vol. 7, Issue 292, pp. 292ra101
DOI: 10.1126/scitranslmed.aaa9186

AIREing out autoimmunity

Patients with autoimmune polyendocrine syndrome type 1(APS1) experience dysfunction in multiple endocrine glands due to mutations in the AIRE gene, which helps promote immune tolerance. These patients frequently are infertile; female infertility can be explained by autoimmune ovarian failure, but the causes of male infertility have remained unclear. Now, Landegren et al. report that the prostatic secretory molecule tranglutaminase 4 (TGM4) is a male-specific autoantigen in APS1 patients that could contribute to subfertility. They found autoantibodies to TGM4 in APS1 patients beginning at puberty, and confirmed in AIRE-deficient mice that TGM4 autoantibodies lead to a destructive prostatitis. These data could help explain infertility in male APS1 patients.

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