IgG, IgA and IgM Antibodies against FSH: Serological Markers of Pathogenic Autoimmunity or of Normal Immunoregulation? Kadri Haller 1 , Christine Mathieu 2 , Kristiina Rull 3 , Kadri Matt 3 , Marie C. Be ´ ne ´ 2 , Raivo Uibo 1 1 Department of Immunology, Institute of General and Molecular Pathology and Centre of Molecular and Clinical Medicine, University of Tartu, Estonia; 2 Laboratoire d’Immunologie du CHU, Faculte ´ de Me ´ decine, Vandœuvre le ` s Nancy, France; 3 Department of Obstetrics and Gynaecology, University of Tartu, Estonia Introduction Autoimmune mechanisms are involved in such infertility disorders as endometriosis and ovarian fail- ure, and may be responsible for the pathophysiology of pre-eclampsia or spontaneous abortions. 1,2 Anti- ovary antibodies (AOA) are associated primarily with premature ovarian failure and unexplained infertil- ity 2,3 and have been found to be markers of autoim- mune disorders causing the poor outcome of in vitro fertilization (IVF). 4,5 As a reference method, indirect immunofluorescence on human or primate frozen ovary sections and the specific labeling of internal theca cells has been used to detect AOA. 6 There have been many hypotheses about the direct anti- genic target in these cells that are involved in ster- oids synthesis. The autoantigenicity of steroidogenic enzymes has been revealed by studies on autoim- mune polyglandular syndrome type I patients who suffered from ovarian failure. These patients presen- ted autoantibodies against enzymes which are also present in internal theca cells. 7 Follicle-stimulating hormone (FSH) and luteinizing hormone receptors of human granulosa cells have also been proposed to have this function, although results are conflicting. 2 Enzyme-linked immunosorbent assay (ELISA) using crude human ovary extract, has been used to detect AOA in patients undergoing IVF procedures. 4 Keywords Autoimmunity, follicle-stimulating hormone, infertility, pregnancy Correspondence Raivo Uibo, Ravila Str. 19, Biomedicum, Tartu 50411, Estonia. E-mail: raivo.uibo@ut.ee Submitted March 4, 2005; revised June 15, 2005; accepted June 24, 2005. Citation Haller K, Mathieu C, Rull K, Matt K, Be ´ ne ´ MC, Uibo R. IgG, IgA and IgM antibodies against FSH: serological markers of pathogenic autoimmunity or of normal immunoregulation? AJRI 2005; 54:262–269 ª Blackwell Munksgaard, 2005 doi:10.1111/j.1600-0897.2005.00306.x Problem Autoimmune mechanisms are often involved in causing infertility. Among the possible targets of autoantibodies, the follicle-stimulating hormone (FSH) which regulates the follicular maturation in human ovary is a promising candidate. We aimed to study whether anti-FSH- antibodies might be involved in different clinical types of infertility. Method of study The study group consisted of 178 patients (75 with polycystic ovary syn- drome (PCOS), 103 with endometriosis) and 75 pregnant women. Female blood donors formed the control group (n ¼ 85). Indirect enzyme-linked immunosorbent assay tests were performed using puri- fied FSH as antigens and a synthetic peptide corresponding to the 78–93 region (V14D) of the human FSH b-chain. Conclusion We showed that anti-FSH-antibodies were present in controls and their production decreased during pregnancy. Endometriosis and PCOS were associated with higher values of anti-FSH-immunoglobulin (Ig)A, anti- V14D-IgA, and endometriosis with anti-V14D-IgG. Our data suggest that anti-FSH-IgA could be a marker of ovarian disorders that cause infertility. ORIGINAL ARTICLE 262 American Journal of Reproductive Immunology 54 (2005) 262–269 ª 2005 Blackwell Munksgaard