TSH receptor antibodies (TRAb) - A potential new biomarker for endometriosis.

OBJECTIVES: The prevalence of several autoimmune diseases, including thyroid dysfunction, has been reported to be increased in patients with endometriosis. Upregulated thyroid stimulation hormone (TSH) receptors in ectopic endometrium and elevated serum titers of TSH receptor antibodies (TRAb) IgG in endometriosis patients indicates an overlap in pathophysiology. However, cross-reactivity with other antibodies must be excluded. The objective of this study was to compare the expression of autoantibodies in women with endometriosis and two control groups to evaluate the potential of TRAb IgG as a diagnostic marker for endometriosis. STUDY DESIGN: This cross-sectional study was carried out in 172 women with surgically confirmed endometriosis and two control groups consisting of 50 healthy blood donors and 114 women from Malmö Offspring Study consisting of people from the general population. Serum levels of thyroid hormones, TSH and TRAb autoantibodies, AXIN1, and autoantibodies against follicle stimulating hormone (FSH), human chorionic gonadotropin (hCG), luteinizing hormone (LH), and their receptors, were analyzed. The patients answered a questionnaire and estimated their gastrointestinal symptoms using the Visual Analogue Scale for Irritable Bowel Syndrome. RESULTS: Of the endometriosis patients, 29.1 % had TRAb IgG above the present detection limit of ≥ 1.0 IE/L compared to 2.6 % of the controls from MOS (p < 0.001) and 94.5 % had levels of TRAb over the previous detection limit ≥ 0.3 IE/L compared to 7.9 % of the controls (p < 0.001). Titers of both TRAb IgG and IgM were increased in patients compared to controls from MOS and blood donors, respectively (p < 0.001). There was no increase of autoantibodies against FSH, FSH receptor (FSHR), hCG, LH, LH receptor (LHR) or TSH compared to the blood donor controls. TRAb titers did not correlate with age, disease duration, AXIN1, TSH, thyroid hormones or gastrointestinal symptoms. CONCLUSION: TRAb IgG and IgM are slightly elevated in patients with endometriosis with no cross-reactivity with other autoantibodies. The results indicate that TRAb is truly elevated and thereby has the potential to be used to support the diagnosing of endometriosis.

Applicability of polygenic risk scores in endometriosis clinical presentation.

BACKGROUND: Risk prediction is an essential part of preventative medicine and in recent years genomic information has become an interesting factor in risk models. Polygenic risk scores (PRS) combine the effect of many genetic variations into a single score which has been shown to have predictive value for many diseases. This study aimed to investigate the association between PRS for endometriosis and the clinical presentation of the disease. METHODS: Women with endometriosis (N = 172) were identified at the Department of Gynecology. All participants answered questionnaires regarding sociodemographic factors, lifestyle habits and medical history, registered bowel symptoms on the Visual Analog Scale for Irritable Bowel Syndrome and passed blood samples. DNA was extracted and samples were genotyped, and a PRS was calculated based on previous genome-wide association studies of endometriosis. Inflammatory proteins and TSH receptor antibodies (TRAb) in serum were analyzed. RESULTS: Inverse associations were identified between PRS and spread of endometriosis, involvement of the gastrointestinal tract and hormone treatment. However, significance was lost when calculated as p for trend and the specificity and sensitivity were low. There were no correlations between PRS and TRAb or inflammatory proteins. CONCLUSION: The findings indicate that specific PRS should be developed to predict clinical presentations in patient with endometriosis.

Associations Between Endometriosis and Gut Microbiota.

The gut microbiota has been associated with many diseases, including endometriosis. However, very few studies have been conducted on this topic in human. This study aimed to investigate the association between endometriosis and gut microbiota. Women with endometriosis (N=66) were identified at the Department of Gynaecology and each patient was matched with three controls (N=198) from the general population. All participants answered questionnaires about socioeconomic data, medical history, and gastrointestinal symptoms and passed stool samples. Gut bacteria were analyzed using 16S ribosomal RNA sequencing, and in total, 58 bacteria were observed at genus level in both patients with endometriosis and controls. Comparisons of the microbiota between patients and controls and within the endometriosis cohort were performed. Both alpha and beta diversities were higher in controls than in patients. With the false discovery rate q<0.05, abundance of 12 bacteria belonging to the classes Bacilli, Bacteroidia, Clostridia, Coriobacteriia, and Gammaproteobacter differed significantly between patients and controls. Differences observed between patients with or without isolated ovarian endometriosis, involvement of the gastrointestinal tract, gastrointestinal symptoms, or hormonal treatment disappeared after calculation with false discovery rate. These findings indicate that the gut microbiota may be altered in endometriosis patients.