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1.
Int J Rheum Dis ; 23(5): 654-660, 2020 May.
Article in English | MEDLINE | ID: mdl-32180363

ABSTRACT

OBJECTIVES: Primary Sjögren's syndrome (pSS) is a chronic autoimmune disease with an unknown etiology. CD200 is associated with many autoimmune diseases, but little is known about its role in pSS. This study aims to correlate the expression of CD200 with pSS and evaluate its significance. METHODS: Plasma CD200, CD200R, and interleukin (IL)-17 levels were measured and analyzed by enzyme-linked immunosorbent assay. Messenger RNA levels of CD200 and CD200R in peripheral blood mononuclear cells (PBMCs) were quantified by quantitative real-time polymerase chain reaction (RT-qPCR). Following pretreatment of CD200-Fc, the protein levels of IL-17A were measured in PBMCs from patients and healthy controls. RESULTS: Results showed that, compared to CD200 in healthy controls, the relative levels in PBMCs from pSS were greater than 2-fold. In addition, CD200 levels in plasma positively correlated with IL-17 levels, as well as between plasma CD200 and pSS activity indexes (including immunoglobulin G and European League Against Rheumatism SS Disease Activity Index). While CD200R levels were significantly decreased in pSS patients, no correlation could be found. Furthermore, the protein level of IL-17 decreased after pretreatment of CD200-Fc in PBMCs from pSS patients. CONCLUSION: Our results suggested that the CD200/CD200R pathway is involved in pSS pathogenesis. It is hypothesized that regulation of IL-17 expression affects Th17 differentiation. This newly discovered pathway could give rise to a novel targeted therapy for pSS.


Subject(s)
Antigens, CD/blood , Leukocytes, Mononuclear/metabolism , Sjogren's Syndrome/blood , Antigens, CD/genetics , Antirheumatic Agents/therapeutic use , Biomarkers/blood , Case-Control Studies , Female , Humans , Immunoglobulin Fc Fragments/therapeutic use , Interleukin-17/blood , Leukocytes, Mononuclear/drug effects , Leukocytes, Mononuclear/immunology , Male , Middle Aged , Orexin Receptors/blood , Orexin Receptors/genetics , Sjogren's Syndrome/diagnosis , Sjogren's Syndrome/drug therapy , Sjogren's Syndrome/immunology , Treatment Outcome , Up-Regulation
2.
Peptides ; 88: 55-61, 2017 02.
Article in English | MEDLINE | ID: mdl-27988352

ABSTRACT

Orexins, also known as hypocretins, play a regulatory role in the sleep-wake cycle by activating orexin receptors. Previous animal studies have shown that sleep deprivation can elevate orexinergic peptide levels. However, the relationship between insomnia disorder and orexin-A levels in humans has not been explored. In the current study, we examined plasma orexin-A levels in patients with insomnia disorder and in normal sleepers. We also studied the possible mechanisms underlying changes in orexin-A levels between the study groups; this included investigations of prepro-orexin and orexin receptor gene polymorphisms as well as exploration of other variables. We measured plasma orexin-A levels in 228 patients with insomnia disorder and 282 normal sleepers. The results indicated that the patients with insomnia disorder had significantly higher orexin-A levels than normal sleepers (63.42±37.56 vs. 54.84±23.95pg/ml). A positive relationship was detected between orexin-A level and age in patients with insomnia disorder. Orexin-A levels were elevated in relation to course of insomnia, as well as in relation to increased Insomnia Severity Index score. None of the evaluated prepro-orexin gene single nucleotide polymorphisms were informative between the two study populations. After sequencing all orexin receptor exons, one variation (rs2271933) in the OX1R gene and one variation (rs2653349) in the OX2R gene were found. However, no significant differences were found in either genotypic or allelic frequency distributions between the two study groups. It is suggested that the increased plasma orexin-A levels in patients with insomnia disorder are associated with the course and severity of insomnia, but not with prepro-orexin and orexin receptor gene polymorphisms.


Subject(s)
Orexin Receptors/genetics , Orexins/blood , Sleep Initiation and Maintenance Disorders/genetics , Adult , Aged , Animals , Female , Genetic Association Studies , Genetic Predisposition to Disease , Humans , Hypothalamus/metabolism , Male , Middle Aged , Orexin Receptors/blood , Polymorphism, Single Nucleotide , Sleep/genetics , Sleep/physiology , Sleep Deprivation/genetics , Sleep Deprivation/physiopathology , Sleep Initiation and Maintenance Disorders/blood , Sleep Initiation and Maintenance Disorders/physiopathology
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