MALT-1 inhibition attenuates the inflammatory response of ankylosing spondylitis by targeting NF-κB activation

Background Mucosa‐associated lymphoid tissue lymphoma translocation protein 1 (MALT1) regulates adaptive and innate immune responses in several inflammatory disease. However, clinical involvement of MALT1 in inflammatory bowel disease (IBD) patients remains unclear. Hence, this study was intended to investigate the correlation of blood MALT1 with disease activity, inflammation indexes as well as treatment response of IBD patients. Methods Blood MALT1 expression in 100 IBD patients [including 25 active (A)‐Crohn's disease (CD) patients, 25 remission (R)‐CD patients, 25 A‐ulcerative colitis (UC) patients, and 25 R‐UC patients] and 25 health controls (HCs) was detected by reverse transcription‐quantitative polymerase chain reaction; besides, serum tumor necrosis factor‐alpha (TNF‐α) and interleukin‐17A (IL‐17A) in IBD patients were detected by enzyme‐linked immunosorbent assay. Results MALT1 was increased in A‐UC patients than in R‐UC patients (p = 0.038) and in HCs (p < 0.001), and also elevated in A‐CD patients than in R‐CD patients (p = 0.048) and in HCs (p < 0.001). MALT1 was positively related to C‐reactive protein (CRP, p = 0.011), TNF‐α (p = 0.036), IL‐17A (p = 0.023), and Mayo score (p = 0.005) in A‐UC patients, CRP (p = 0.017), erythrocyte sedimentation rate (p = 0.033), TNF‐α (p = 0.004), and Crohn's disease activity index score (p = 0.028) in A‐CD patients. But MALT1 was not correlated with either inflammation indexes or disease activity score in R‐UC and R‐CD patients. MALT1 gradually declined from baseline to W12 in A‐UC and A‐CD patients (both p < 0.001). Moreover, MALT1 at W4 (p = 0.031) and W12 (p = 0.003) in A‐UC patients as well as MALT1 at W12 (p = 0.008) in A‐CD patients associated with clinical response. Conclusion MALT1 serves as a potential biomarker for disease surveillance and treatment response prediction of IBD patients.

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Potential role of MALT1 as a candidate biomarker of disease surveillance and treatment response prediction in inflammatory bowel disease patients

Wu¹,

2022

“… 10 According to previous studies, MALT1 is a vital regulator of immune diseases. 11 , 12 , 13 , 14 , 15 For instance, suppressing MALT1 represses osteoclast differentiation while alleviating pathologic bone erosion and synovitis in RA model mice. 11 Meanwhile, MALT1 knockdown inhibits the expression of pro‐inflammatory cytokines and chemokines in human primary keratinocytes, thus regulating the progression of psoriasis.…”

Section: Introductionmentioning

confidence: 99%

“… 12 , 13 Besides, inhibiting MALT1 also reduces the levels of inflammatory cytokines through suppressing nuclear factor‐κB (NF‐κB) pathway in inflammatory bowel disease or ankylosing spondylitis model mice. 14 , 15 Clinically, two very recent studies report that MALT1 is positively correlated with inflammation, disease activity, and clinical response in patients with inflammatory bowel disease or RA. 16 , 17 However, whether MALT1 could serve as a biomarker reflecting treatment response to TNF inhibitors in RA remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Mucosa‐associated lymphoid tissue lymphoma translocation protein 1 in rheumatoid arthritis: Longitudinal change after treatment and correlation with treatment efficacy of tumor necrosis factor inhibitors

Wang

Liu

Xiang

et al. 2022

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.

MALT1 positively relates to Th17 cells, inflammation/activity degree, and its decrement along with treatment reflects TNF inhibitor response in ankylosing spondylitis patients

Yuan

Xiang

Wang

et al. 2022

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.