Abstract
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.
Highlights
Clinical experimental [1,2,3] and prospective epidemiological studies [4] suggest that dysregulation of adrenocortical or gonadal function may predispose to developing rheumatoid arthritis (RA)
Multicompartmental relative adrenocortical insufficiency was suspected in a minority subset of pre-RA women, which may predispose to developing the disease [4]
The aim of this study was to analyze a large community cohort database for relations of age and sex to both neuroendocrine and immunologic (NEI) biomarkers, as they may relate to sexual dimorphism and predisposition to clinical onset of RA
Summary
Clinical experimental [1,2,3] and prospective epidemiological studies [4] suggest that dysregulation of adrenocortical or gonadal function may predispose to developing rheumatoid arthritis (RA). Serum adrenal androgen (AA) steroid levels were lower in a minority of women who had premenopausal onset of disease, compared to matched control (CN) females [2]. A greater minority of women who subsequently developed rheumatoid arthritis (pre-RA cases) had combined low serum cortisol and low androstenedione concentrations than matched cohort CN females [4]. In a separate case-control cohort study of blood donors in Netherlands [9], slightly higher median CRP concentrations were found in multiple serum samples from 79 pre-RA compared to 79 matched CN subjects. Inflammatory cytokines, and other immunological components differ by age and sex and may be related to such host predispositions in International Journal of Endocrinology inflammatory diseases, like RA [8]. The aim of this study was to analyze a large community cohort database for relations of age and sex to both neuroendocrine and immunologic (NEI) biomarkers, as they may relate to sexual dimorphism and predisposition to clinical onset of RA
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