Elevated levels of TRAb IgG autoantibodies are not recognized in endometriosis by current clinical methods

Agnes Petersson^1,2*Bodil Roth²Charlotte Becker³Bodil Ohlsson^1,2

• ¹Department of Clinical Sciences Malmö, Faculty of Medicine, Lund University, Malmö, Sweden
• ²Department of Internal Medicine, Skåne University Hospital, Malmö, Sweden
• ³Department of Clinical Chemistry and pharmacology, University Laboratory, Skåne, Sweden

Background: Endometriosis can cause gastrointestinal symptoms that sometimes lead to incorrect diagnosis of irritable bowel syndrome (IBS). Receptors of thyroid stimulating hormone (TSH) are found in the endometrium and are overexpressed in ectopic endometrium. The role of TSH receptors and thyroid hormones in the pathophysiology of endometriosis has therefore been discussed. No biomarker is available for endometriosis diagnosis, but findings of TSH receptor antibodies (TRAb) have been found by two different methods. The aim of the study was to confirm that TRAb IgG levels are elevated in patients with endometriosis compared with IBS and healthy controls. Methods: 121 patients with a diagnosis of endometriosis, two cohorts with 50 IBS patients and 50 healthy controls were recruited. All subjects had to fulfill study questionnaires regarding sociodemographic factors, lifestyle, medical history and gastrointestinal symptoms. Blood samples were drawn and TRAb IgG was analyzed in serum at the Departments of Clinical Chemistry at Sahlgrenska University Hospital with BRAHMS TRAK Human assay from Thermoscientific and at Skåne University Hospital with the Elecsys Anti-TSHR assay from Roche Diagnostics. Both methods are developed and used clinically to diagnose Graves' disease with high specificity. Results: Patients with endometriosis had highest BMI (p=0.001) and prevalence of hypothyroidism (p=0.005). Endometriosis and IBS patients had many gastrointestinal symptoms, in contrast to the healthy controls. There was no significant difference in number of patients with detectable serum TRAb between endometriosis patients (n=10, 8.3%) and controls (n=2, 4%) (p=0.512) or IBS patients (n=3, 6%) (p=0.758) in Gothenburg. Similar results were found when TRAb was analyzed in serum in Malmö, with the same prevalence of TRAb in endometriosis patients (n=4, 4.9%) as in controls (n=4, 8.0%) (p=0.710) and IBS patients (n=4, 8.0%) (p=0.710). Conclusions: In conclusion, the available tests in clinical routine could not reveal elevated levels of TRAb in the current exploratory study. Thus, TRAb cannot yet be used clinically as a biomarker of endometriosis. Still, other variants of antibody tests may be used in a laboratory experimental setting. The role of TSH receptors and TRAb in the pathophysiology of endometriosis deserves further research.