Blood MALT1, Th1, and Th17 cells are dysregulated, inter‐correlated, and correlated with disease activity in rheumatoid arthritis patients; meanwhile, MALT1 decline during therapy relates to treatment outcome

Abstract

Objective Mucosa‐associated lymphoid tissue lymphoma translocation protein 1 (MALT1) participates in inflammatory and autoimmune diseases via activating various signaling pathways and promoting the differentiation of T‐helper (Th) 1 and Th17 cells; however, it is rarely reported in rheumatoid arthritis (RA). This study aimed to assess the correlation of MALT1 with Th1 and Th17 cells and evaluate its potential as a biomarker for evaluating disease activity and treatment outcomes in RA patients. Methods This study enrolled 139 RA patients and 45 health controls (HCs); then, blood MALT1, Th1, and Th17 cells were determined. For RA patients only, blood MALT1 at week (W) 6 and W12 after treatment was also detected. Additionally, clinical response and remission of RA patients were assessed at W12. Results MALT1 (p < 0.001), Th1 (p = 0.011), and Th17 (p < 0.001) cells were all increased in RA patients than HCs; meanwhile, increased MALT1 was associated with elevated Th1 (p = 0.003) and Th17 (p < 0.001) cells in RA patients. Besides, MALT1, Th1, and Th17 cells were positively correlated with parts of disease activity indexes in RA patients (all p < 0.050). In addition, MALT1 was gradually declined from W0 to W12 (p < 0.001) in RA patients. Specifically, MALT1 at W6 and W12 was lower in response patients than no response patients (both p < 0.010), also in remission patients than no remission patients (both p < 0.050). Conclusion MALT1, Th1, and Th17 cells are dysregulated, inter‐correlated, and correlated with disease activity in RA patients; meanwhile, the decline of MALT1 expression can partly reflect RA treatment response and remission.

Aberrant blood MALT1 and its relevance with multiple organic dysfunctions, T helper cells, inflammation, and mortality risk of sepsis patients

“…Several previous studies disclose that MALT1 leads to T cell activation and differentiation into Th1 and Th17 cells in a series of infection‐associated diseases including colitis and encephalitis 21,25,26 . In the current study, PBMC MALT1 expression was positively associated with Th17 cells, IL‐17A level in sepsis patients, but not with Th1 cells or IFN‐γ level.…”

“…Interestingly, discriminating value of MALT1 is similar to that of Th1 cells, IFN‐γ, Th17 cells, and IL‐17A; meanwhile, the discriminating value of MALT1 is somehow inferior to that of APACHE II score and SOFA score, which implies that MALT1 could serve as an assistant prognostic biomarker for sepsis. Possible explanations could be that: (1) MALT1 enhances the differentiation of Th1 cells and Th17 cells as well as their secreted cytokines, whose abnormal expressions are linked with aggravated sepsis severity and thereby be linked with elevated mortality risk 21,25–27 . Thus, elevated MALT1, together with Th1 cells, Th17 cells, and IL‐17A, is correlated with higher mortality risk in sepsis patients.…”

“…In detail, the total RNA from PBMC was extracted using PureZOL RNA isolation reagent (Bio‐Rad); complementary DNA was synthesized by iScript™ cDNA Synthesis Kit (with random primer) (Bio‐Rad); qPCR was performed by SYBR ® Green Realtime PCR Master Mix (Toyobo). Besides, the current primers took reference from a previous study 21 . Additionally, glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH) was used as the internal reference; meanwhile, 2 −ΔΔCt method was applied to calculate the MALT1 relative expression.…”

“…Besides, the current primers took reference from a previous study. 21 Additionally, glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH) was used as the internal reference; meanwhile, 2 −ΔΔCt method was applied to calculate the MALT1 relative expression.…”

“…Beyond that, MALT1 overexpression could result in kidney injury via activating nuclear factor κB (NF‐κB) signaling 15 . Additionally, it is illustrated that MALT1 enhances the differentiation of CD4 + T cells into Th1 and Th17 cells, meanwhile the differentiation of CD4 + T cells into Th1 and Th17, which are important in the pathology of sepsis 18–21 . However, the clinical relevance of MALT1 with sepsis, which is one of the most serious infection‐related diseases, still remains elusive.…”