Elevated levels of TL1A are associated with disease activity in patients with systemic sclerosis

Abstract

TL1A is a member of the TNF superfamily. It performs significantly in the pathogenesis of rheumatic and autoimmune diseases partly through regulating the Th17 pathway. The clinical implication of circulating TL1A in patients with systemic sclerosis (SSc) remains unclear, and correlation between TL1A and Th17-related cytokines in the pathogenesis of SSc needs to be discussed. We measured serum levels of TL1A and Th17-related cytokines by ELISA in 47 patients with SSc, 56 patients with SLE, and 53 healthy subjects, and investigated association of these cytokines with clinical manifestations and laboratory variables. TL1A in relation to Th17-related cytokines were examined. In addition, the transcript level of TL1A in peripheral blood mononuclear cells (PBMCs) was determined by real-time reverse transcription polymerase chain reaction (real-time PCR). Serum TL1A levels were higher in patients with SSc than in healthy controls (P = 0.001), but were lower compared with SLE patients (P = 0.004). Diffuse cutaneous SSc or limited cutaneous SSc patients reported elevated expression of TL1A than those in healthy controls (P = 0.002, P = 0.007). Patients with active disease showed significantly higher expression of TL1A when compared with less active disease (P = 0.014). SSc patients with arthritis, elevated IgG titer, ESR >30 mm/h, and CRP >5 mg/l displayed elevated expression of TL1A, respectively. Serum levels of IL-17 and IL-21 were increased in SSc patients compared with healthy controls and positively related to TL1A levels (r = 0.373, P = 0.010; r = 0.370, P = 0.011, respectively). Moreover, TL1A mRNA expression in PBMCs was significantly higher in patients with SSc compared with healthy controls (P < 0.001). TL1A may play a role in the development of SSc.

Association between TL1A gene polymorphisms and systemic lupus erythematosus in a Chinese Han population

“…AS patients treated with anti-TNF monoclonal antibodies revealed strongly reduced serum levels of TL1A when compared with the patients without treatment (Konsta et al, 2013). In our previous studies, we found elevated serum levels of TL1A in lupus patients as compared with healthy controls and patients with systemic sclerosis (Xu, Chen, Li, Ren, & Ye, 2015;Xu et al, 2017). However, whether gene polymorphisms of TL1A are related to SLE susceptibility remains to be elucidated.…”

Circulating TNF-like protein 1A (TL1A) is elevated early in rheumatoid arthritis and depends on TNF

“…Elevated serum TL1A has been reported in an AS [31], and TNFSF15 polymorphisms have been suggested to be linked to the risk for SpA and AS [32,33]. Serum TL1A has previously been reported to be elevated in SLE and to a lesser extent, in systemic sclerosis [34,35], but it is difficult to compare the degree of elevation in serum TL1A across studies. The lack of consistent elevation of TL1A in patients with hepatitis C even in the presence of circulating immune complexes and/or RF suggests that there may be additional stimuli for TL1A production in RA, such as activation of Toll-like receptors by endogenous ligands in the joint [36].…”

Novel mechanisms and clinical trial endpoints in intestinal fibrosis*

“…146 Primary intestinal myofibroblasts express DR3 and functionally respond to direct TL1A signaling by increasing collagen. 146 In a recent study, TL1A overexpressing naïve 150 IL-17A is significantly overexpressed in CDstrictured areas compared with non-strictured areas. 151 In addition, IL-17A significantly inhibits myofibroblast migration and promotes the production of MMP-3, MMP-12, TIMP-1, and collagen by myofibroblasts from strictured CD tissues.…”

“…148 Th17 cell numbers and Th17related cytokines, including IL-17, IL-21 and IL-22, are significantly increased in active IBD. 150 IL-17A is significantly overexpressed in CDstrictured areas compared with non-strictured areas. 151 In addition, IL-17A significantly inhibits myofibroblast migration and promotes the production of MMP-3, MMP-12, TIMP-1, and collagen by myofibroblasts from strictured CD tissues.…”

“…In humans, IL‐6, IL‐21, IL‐23, IL‐1β, and TGF‐β are critical for Th17 development and, in addition to IL‐17A‐F, Th17 cells also produce IL‐21, IL‐22, IL‐9, IL‐26, TNF‐α, and chemokine (C‐C motif) ligand 20 (CCL20) 148 . Th17 cell numbers and Th17‐related cytokines, including IL‐17, IL‐21 and IL‐22, are significantly increased in active IBD 150 . IL‐17A is significantly overexpressed in CD‐strictured areas compared with non‐strictured areas 151 .…”