No 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.

Idiopathic hypoparathyroidism (iH-PoPT) is a rare condition infrequently associated with axial spondyloarthritis (SpA) which may mimic ankylosing spondylitis (AS). Axial SpA is a unifying clinical term for chronic inflammatory spinal disorders, although biomechanical factors may play a role. The primary objective of this review is to critically describe the iHPoPT/SpA phenotype defined by established criteria and its differentiation from AS. Five databases were comprehensively searched without time limit to retrieve 14 (11M, 3F) iH-PoPT/SpA cases. Their demographic, clinical, laboratory, radiographic, and HLA-B27 status were compared to two national series of AS patients. Mean (SD) onset age of musculoskeletal symptoms [32.5 (9.7)] was significantly older than 943 German AS patients [25.1 (8.5), (p=0.004)] and 842 Spanish AS patients [26.1 (9.7), (p=0.030)]. Radiographic lesions of iHPoPT/SpA differ morphologically from skeletal alterations in hyperparathyroid and hypophosphataemic syndromes which often have inadequate bone mineralisation and decreased bone mineral density (BMD). Clinical musculoskeletal manifestations were greater (p<0.001) in iHPoPT/SpA than AS patients at cervical (62 vs. 10%) and hip (85 vs. 22%) localisations, respectively. Typical AS sacroiliac joint structural lesions of erosions and bony bridging were reported in only 1 iHPoPT/SpA case and HLA-B27 was positive in 2 of 10 tested. The iHPoPT/SpA phenotype may be a natural experiment on the novel concept of how chronic hypocalcaemia of iHPoPT causes axial neuromotor hypercontractility and biomechanically induces the rare SpA association. In iHPoPT/SpA, neuromuscular hyper-contractility may predispose to axial radiographic enthesopathy lesions and contribute knowledge on biomechanical contributions and pathways for further research.