Sexual Dimorphisms of Adrenal Steroids, Sex Hormones, and Immunological Biomarkers and Possible Risk Factors for Developing Rheumatoid Arthritis

Innate immunity and immunological biomarkers are believed to be interrelated with sex hormones and other neuroendocrine factors. Sexual dimorphism mechanisms may be operating in certain rheumatic and inflammatory diseases which occur more frequently in women than men, as rheumatoid arthritis (RA). Less data have been available on altered interrelations of the combined neuroendocrine and immune (NEI) systems as risk factors for development of certain diseases. In this study, serological interrelations of NEI biomarkers are analyzed before symptomatic onset of RA (pre-RA) versus control (CN) subjects, stratified by sex. Sexual dimorphism was found in serum levels of acute serum amyloid A (ASAA), soluble interleukin-2 receptor alpha (sIL-2Rα), and soluble tumor necrosis factor receptor 1 (sTNF-R1). Multiple steroidal and hormonal (neuroendocrine) factors also showed highly (p < 0.001) significant sexual dimorphism in their assayed values, but less for cortisol (p = 0.012), and not for 17-hydroxyprogesterone (p = 0.176). After stratification by sex and risk of developing RA, differential NEI correlational patterns were observed in the interplay of the NEI systems between the pre-RA and CN groups, which deserve further investigation.