Background Mucosa‐associated lymphoid tissue lymphoma translocation protein 1 (MALT1) correlates with treatment outcomes in inflammatory bowel disease and rheumatoid arthritis (RA). This study aimed to further evaluate the MALT1 longitudinal change and its relationship with tumor necrosis factor inhibitors (TNFi) response in RA patients. Methods Seventy‐one RA patients receiving TNFi [etanercept ( n = 42) or adalimumab ( n = 29)] were enrolled. MALT1 was detected by RT‐qPCR in peripheral blood samples of RA patients before treatment (W0), at week (W)4, W12, and W24 after treatment. RA patients were divided into response/non‐response, remission/non‐remission patients according to their treatment outcome at W24. Meanwhile, MALT1 was also detected by RT‐qPCR in 30 osteoarthritis patients and 30 healthy controls (HCs). Results Mucosa‐associated lymphoid tissue lymphoma translocation protein 1 was elevated in RA patients compared with HCs ( Z =−6.392, p < 0.001) and osteoarthritis patients ( Z = −5.020, p < 0.001). In RA patients, MALT1 was positively correlated with C‐reactive protein ( r s = 0.347, p = 0.003), but not other clinical characteristics, treatment history, or current TNFi category. Meanwhile, MALT1 decreased from W0 to W12 in total RA patients ( x 2 = 86.455, p < 0.001), etanercept subgroup ( x 2 = 46.636, p < 0.001), and adalimumab subgroup ( x 2 = 41.291, p < 0.001). Moreover, MALT1 at W24 ( p = 0.012) was decreased in response patients compared with non‐response patients; MALT1 at W12 ( p = 0.027) and W24 ( p = 0.010) were reduced in remission patients than non‐remission patients. In etanercept subgroup, MALT1 at W24 ( p = 0.013) was decreased in response patients compared with non‐response patients. In adalimumab subgroup, MALT1 at W24 ( p = 0.015) was lower in remission patients than non‐remission patients. Conclusion Mucosa‐associated lymphoid tissue lymphoma translocation protein 1 reduction after treatment is associated with response and remission to TNFi in RA patients.

Background Rheumatoid arthritis (RA) is a chronic inflammatory disease. Abnormal proliferation and inflammation of fibroblast-like synoviocytes (FLSs) are the main pathological features of the disease. Accumulating studies have identified that circular RNAs (circRNAs) were involved in the progression of RA. Our study was to assess the function and mechanism of circ_0083964 in RA. Methods Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot were utilized to test the level of circ_0083964, miR-204-5p and YY1. Counting Kit-8 (CCK-8) assay, EdU assay, flow cytometry, transwell assay and wound-healing assay were utilized to test cell viability, proliferation, apoptosis, invasion and migration. Cell inflammation was estimated with enzyme-linked immunosorbent assay (ELISA) kits. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were employed to identify the target relationship between miR-204-5p and circ_0083964 or YY1. Results Circ_0083964 was highly expressed in RA synovial tissues and RA-FLSs. Circ_0083964 downregulation constrained proliferation, metastasis and inflammation and facilitated apoptosis in RA-FLSs. Furthermore, circ_0083964 served as a sponge of miR-204-5p, and rescue experiments proved that miR-204-5p deficiency overturned the suppressive impacts of circ_0083964 silencing on RA-FLSs progression. Additionally, we also verified that YY1 could be targeted by miR-204-5p, and its overexpression rescued the repressive impact of miR-204-5p introduction on RA-FLSs development. Besides that, we revealed that circ_0083964 mediated YY1 expression by regulating miR-204-5p. Conclusion Circ_0083964 inhibition confined RA development by sponging miR-204-5p to hamper the YY1 level, which will provide a theoretical basis for the treatment of RA.

Background: Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) facilitates CD4 + T-cell differentiation, immune response, inflammation, and osteoclastogenesis. This study aimed to explore the relation between MALT1 and treatment efficacy to tumor necrosis factor inhibitor (TNFi) in ankylosing spondylitis (AS) patients. Methods: This study recruited 73 AS patients underwent adalimumab treatment.Peripheral blood mononuclear cell (PBMC) was obtained at Week (W) 0, W4, W8, and W12 after treatment initiation; then, MALT1 was measured using RT-qPCR. Furthermore, PBMC and serum at W0 were proposed to flow cytometry and ELISA for Th1 cells, Th17 cells, IFNγ, and IL-17A levels measurement. Besides, 20 osteoarthritis patients and 20 healthy controls (HCs) were enrolled to detect MALT1.Results: Mucosa-associated lymphoid tissue lymphoma translocation protein 1 expression was higher in AS patients compared with HCs (p < 0.001) and osteoarthritis patients (p < 0.001). Besides, MALT1 expression was positively linked with CRP (p = 0.002), BASDAI (p = 0.026), PGADA (p = 0.040), ASDAS CRP (p = 0.028), Th17 cells (p = 0.020), and IL-17A (p = 0.017) in AS patients, but did not relate to other clinical features, Th1 cells or IFNγ (all p>0.050). MALT1 was decreased along with treatment only in AS patients with ASAS40 response (p < 0.001), but not in those without ASAS40 response (p = 0.064). Notably, MALT1 expression was of no difference at W0 (p = 0.328), W4 (p = 0.280), and W8 (p = 0.080), but lower at W12 (p = 0.028) in AS patients with ASAS40 response compared with those without ASAS40 response. Conclusion:Mucosa-associated lymphoid tissue lymphoma translocation protein 1 positively correlates with Th17 cells, inflammatory, and activity degree; meanwhile, its decrement along with treatment reflects the response to TNF inhibitor in AS patients.