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Objective: Ankylosing spondylitis (AS) and rheumatoid arthritis (RA) are chronic inflammatory joint diseases, linking to the alterations of immune cells. We attempted to assess whether the alterations in the composition of CD4+/CD8+ T cells are different between AS and RA and identify the characteristic cells between male and female patients. Methods: The proportions of CD3+ or double positive T cells, 6 CD4+ T subsets and 9 CD8+ T cell subsets were detected by flow cytometry and compared in 30 healthy individuals, 42 AS patients and 45 RA patients. The differentially altered cells were individually analyzed for associations with disease activity parameters. In addition, their proportions were compared between different genders in the 3 groups. Results: The proportions of CD4+ T cells, naive CD4+ T cells and central memory CD4+ T cells were lower in AS patients (P = 0.001, P = 0.002 and P = 0.007, respectively) and RA patients (P = 0.032, P < 0.001 and P = 0.016, respectively), but the proportion of effector memory ones was higher when compared with healthy populations (both P < 0.001), as were the decrease of naive/central memory CD8+ T cells in AS (P = 0.003 and P = 0.016, respectively) and RA (P < 0.001 and P = 0.006, respectively), and the increased tendency of terminally differentiated CD8+ T cells. However, these above‐mentioned cells, regulatory T (Treg) cells and CD8+ T cells with different CD127 expressions between AS and RA were similar in proportion. Furthermore, naive CD4+ T cells were positively associated with C‐reactive protein (CRP) in AS, whereas CD4+ T cells and terminally differentiated CD8+ T of RA patients were associated with CRP in RA. The gender‐related alterations predominantly displayed the overexpressions of Treg cells and naive CD8+ T cells in female patients with AS and RA, respectively. Conclusions: AS patients and RA patients have some similar peripheral CD4+/CD8+ T cell subsets but are distinct from healthy individuals, which may contribute to disease severity. Females are respectively characterized by the up‐regulation of Treg cells and naive CD8+ T cells in AS patients and RA patients. The study offers an in‐depth understanding of the role of T cell subsets in the similarities of the disorders and helps us to monitor disease changes and may offer a theoretical basis of developing novel therapies against common targets. [ABSTRACT FROM AUTHOR]

Objective: Previous studies have shown that human leukocyte antigen (HLA)‐B27 induces the accumulation of unfolded proteins in the endoplasmic reticulum (ER) to cause ER stress, resulting in the unfold protein response (UPR), apoptosis and autophagy. However, it is still unknown whether it affects the survival of monocytes. In this study, we attempted to examine the effect of HLA‐B27 gene knockout on the proliferation and apoptosis of THP‐1 monocytic cell line and its potential mechanism. Methods: HLA‐B27 gene knockout THP‐1 cell line was constructed by lentivirus infection, and knockout efficiency was detected by immunofluorescence, quantitative reverse transcription ‐ polymerase chain reaction (qRT‐PCR) and western blot. Cell Counting Kit‐8 (CCK‐8) method and Annexin‐V/PI double staining were used to detect the proliferation and apoptosis of the constructed THP‐1 cell line, respectively. qRT‐PCR was used to detect the effect of HLA‐B27 inhibition on the expressions of ER molecular chaperone binding immunoglobulin protein (BiP) and genes about the UPR pathway. The proliferation rate of human BiP protein‐stimulated THP‐1 cells was detected by CCK‐8 method. Results: HLA‐B27 gene knockout THP‐1 cells were successfully constructed by lentivirus infection. Knockout of HLA‐B27 effectively promoted the proliferation of THP‐1 cells and inhibited the apoptosis induced by cisplatin. qRT‐PCR showed that BiP was synchronously increased, while activation of UPR pathway was inhibited. Stimulation with human BiP promoted the proliferation of THP‐1 cells in a concentration‐dependent manner. Conclusions: HLA‐B27 inhibition can promote the proliferation and inhibit the apoptosis of THP‐1 cells. The inhibition function may be achieved through promotion of BiP and inhibition of UPR pathway activation. [ABSTRACT FROM AUTHOR]

Aim: Genetic factors are believed to be implicated in the pathogenesis of relapsing polychondritis (RP). However, the molecular genetic determinants remain to be elucidated. This study aimed to detect the susceptibility genes of RP with whole‐exome sequencing (WES) in a Chinese family and deepen our understanding of the pathogenesis of RP thereafter. Method: A 32‐year‐old Chinese female proband with RP and her family including her mother with RP were enrolled in the study. The genomic DNA of 6 human subjects was extracted from peripheral blood and then gene allele mutations were identified using WES. Candidate variants with low frequency (<0.1%) in the general population and predicted deleterious effects on gene function were identified. Sanger sequencing was applied subsequently to confirm the analyzed gene variants in 12 human blood samples. Results: Nine single nucleotide polymorphism variants from different genes were identified to associate with RP by WES and further confirmed by Sanger sequencing, including Ring finger protein 207 (RNF207), collagen type XXII alpha 1 chain (COL22A1) rs200464636, glycosylphosphatidylinositol anchor attachment 1 (GPAA1) rs201424010, recQ like helicase 4 (RECQL4) rs757703895, folliculin (FLCN) NM_144606: c.G838A: p.E280K, DNA ligase 3 (LIG3) rs761808558, NM_207396: c.T425C:p.I142T, myosin heavy chain 15 (MYH15) NM_014981: c.G4462A: p.A1488T, purkinje cell protein 2 (PCP2) rs144974437 and coiled‐coil domain containing 61 (CCDC61) rs777816675. Conclusions: This study suggests that coinheritance of multigene mutation may contribute to RP predisposition. The candidate genes mutated which we discovered are potential targets for in‐depth functional studies. [ABSTRACT FROM AUTHOR]