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

Abstract

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.

MALT1 in asthma children: A potential biomarker for monitoring exacerbation risk and Th1/Th2 imbalance‐mediated inflammation

“…Hence, MALT1 was positively related to IgE in children with asthma exacerbation. (2) MALT1 was possibly associated with sustained inflammatory flare, which led to severe lung injury, then the exacerbation severity was correspondingly aggravated 15,41 . Thus, MALT1 was negatively correlated with FEV 1 /FVC and positively associated with exacerbation severity in children with asthma exacerbation.…”

“…For instance, one study finds that MALT1 leads to T‐cell activation and promotes it differentiating into Th2 cells via combining with B‐cell lymphoma 10 (BCL‐10), which further exacerbates the peanut allergy 32 . Another study supports that MALT1 is positively associated with TNF‐α, C‐reactive protein in inflammatory bowel disease patients 15 . Nevertheless, it is rarely reported the correlation of MALT1 with Th1/Th2 imbalance and inflammatory cytokines in asthma children.…”

“…Some evidence exhibits that MALT1 regulates T‐cell homeostasis and inflammation response in some immune‐mediated diseases (including peanut allergy, inflammatory bowel disease, etc.). 15 , 28 , 31 , 32 For instance, one study finds that MALT1 leads to T‐cell activation and promotes it differentiating into Th2 cells via combining with B‐cell lymphoma 10 (BCL‐10), which further exacerbates the peanut allergy. 32 Another study supports that MALT1 is positively associated with TNF‐α, C‐reactive protein in inflammatory bowel disease patients.…”

“… 32 Another study supports that MALT1 is positively associated with TNF‐α, C‐reactive protein in inflammatory bowel disease patients. 15 Nevertheless, it is rarely reported the correlation of MALT1 with Th1/Th2 imbalance and inflammatory cytokines in asthma children. Besides, the previous studies have observed that MALT1 correlates with TNF‐α and IL‐6 in other allergic diseases, while the latter two factors also modulate inflammation and involve in the development of asthma.…”

“…Mucosa‐associated lymphoid tissue lymphoma translocation protein 1 (MALT1), a cysteine protease expressed in T cells, B cells, and innate immune cells, is known for its dual functions (scaffold function and proteolytic activity), which is reported as a crucial regulator in allergic response. 12 , 13 , 14 , 15 , 16 A systematic review supports that MALT1 plays an essential role in T helper (Th)2‐mediated allergy via disturbing the homeostasis of T cells and refining proinflammatory signaling. 14 Also, one study reports that the protease activity of MALT1 regulates the attenuation of Th1 cells in human peripheral T cells.…”