Transglutaminase 4 as a prostate autoantigen in male subfertility

LANDEGREN N; SHARON D; SHUM AK; KHAN IS; FASANO KJ; HALLGREN Å; KAMPF C; FREYHULT E; ARDESJÖ-LUNDGREN B; ALIMOHAMMADI M; RATHSMAN S; LUDVIGSSON JF; LUNDH D; MOTRICH R; RIVERO V; FONG L; GIWERCMAN A; GUSTAFSSON J; PERHEENTUPA J; HUSEBYE ES; ANDERSON MS; SNYDER M; KÄMPE O

Science Translational Medicine

Science/AAAS

Lugar: Washington; Año: 2015 vol. 7

1946-6242

utoimmune polyendocrine syndrome type 1 (APS1), a monogenic disorder caused by AIRE gene mutations, features multiple autoimmune disease components. Infertility is common in both males and females with APS1. Although female infertility can be explained by autoimmune ovarian failure, the mechanisms underlying male infertility have remained poorly understood. We performed a proteome-wide autoantibody screen in APS1 patient sera to assess the autoimmune response against the male reproductive organs. By screening human protein arrays with male and female patient sera and by selecting for gender-imbalanced autoantibody signals, we identified transglutaminase 4 (TGM4) as a male-specific autoantigen. Notably, TGM4 is a prostatic secretory molecule with critical role in male reproduction. TGM4 autoantibodies were detected in most of the adult male APS1 patients but were absent in all the young males. Consecutive serum samples further revealed that TGM4 autoantibodies first presented during pu