Antigenic cross-reactivity of human tracheal mucin with human sperm and trophoblasts correlates with the expression of mucin 8 gene messenger ribonucleic acid in reproductive tract tissues

Objective: To test whether autoimmunity to sperm in men with cystic fibrosis (CF) is a result of cross-reactivity between sperm and carbohydrate sequences of the abnormal CF mucins, we investigated the possible epitope sharing between sperm surface antigens and CF mucin antigens using specific monoclonal antibodies (mAbs) directed to purified CF tracheobronchial mucin-1 (HTM-1) and the expression of tracheal mucin 8 gene (MUC8) mRNA in normal male and female reproductive tract tissues by Northern blot analysis. Design: A panel of mAbs directed to HTM-1 subspecies (types I to V) and polyclonal antibodies (pAb) to native and deglycosylated HTM-1 were tested for their ability to agglutinate motile sperm. An indirect immunofluorescence assay was used to detect expression of cross-reactive HTM-1 epitopes on sperm, term placenta (n = 3), and purified trophoblasts (n = 9). Northern blot analysis was used to detect MUC8 messenger RNA (mRNA) in male and female reproductive tract tissues. Setting: University of Oklahoma Health Sciences Center, a tertiary care referral center. Main Outcome Measures: The demonstration of cross-reactive mucin at the protein and mRNA levels in reproductive tract tissues. Results: Of the five mucin subspecies, type II, IV, and V mucin-specific mAbs (21.3, 33.3, and 54.1) induced head-to-head agglutination of motile sperm; pAb to deglycosylated mucin had no effect. Sperm agglutination mediated by type IV mucin mAb 33.3 was abrogated completely by D-mannose. Within the term placental villi, type II mucin was localized to fetal endothelium, type IV mucin was localized to syncytiotrophoblast, and type V mucin was localized to cytotrophoblasts. Immunologic studies correlated with the results of Northern blot analysis, which revealed strong MUC8 mRNA expression in the human testis, placenta, endometrium, and cervix and weak or undetectable levels in the human epididymis, seminal vesicle, ovary, fallopian tube, and uterus. Conclusions: Both male and female reproductive tract tissues synthesize tracheal MUC8 mucin. Monoclonal antibodies specific to human tracheal mucin subtypes induced ''immune-type'' agglutination of motile sperm. Therefore, expression of cross-reactive MUC8 mucin epitopes in reproductive tract tissues may contribute to the development of low affinity, carbohydrate-specific, agglutinating antisperm antibodies in the genital tract.