Association of anti-TNF-α treatment with gut microbiota of patients with ankylosing spondylitis.

OBJECTIVE: Gut dysbiosis contributes to multiple autoimmune diseases, including ankylosing spondylitis, which is commonly treated with tumor necrosis factor (TNF)-α inhibitors (TNFis). Because host TNF-α levels are considered to interact with gut microbiota, we aimed to systematically investigate the microbiota profile of ankylosing spondylitis patients with anti-TNF-α-based treatment and identify potential key bacteria. METHODS: Fecal samples were collected from 11 healthy controls and 24 ankylosing spondylitis patients before/after anti-TNF-α treatment, the microbiota profiles of which were evaluated by 16S ribosomal DNA amplicon sequencing and subsequent bioinformatic analysis. RESULTS: Significantly different microbial compositions were observed in samples from ankylosing spondylitis patients compared with healthy controls, characterized by a lower abundance of short-chain fatty acid (SCFA)-producing bacteria. All patients exhibited a positive response after anti-TNF-α treatment, accompanied by a trend of restoration in the microbiota compositions and functional profile of ankylosing spondylitis patients to healthy controls. In particular, the abundance of SCFA-producing bacteria (e.g. Megamonsa and Lachnoclostridium ) was not only significantly lower in ankylosing spondylitis patients than in healthy controls and restored after anti-TNF-α treatment but also negatively correlated with disease severity (e.g. cor = -0.52, P = 8 × 10 -5 for Megamonsa ). In contrast, Bacilli and Haemophilus may contribute to ankylosing spondylitis onset and severity. CONCLUSIONS: Microbiota dysbiosis in ankylosing spondylitis patients can be restored after anti-TNF-α treatment, possibly by impacting SCFA-producing bacteria.

Evaluation of biomarkers related to endothelial dysfunction: proof of vasculopathy in anti-melanoma differentiation-associated gene 5 dermatomyositis.

OBJECTIVES: We aimed to reveal evidence of endothelial dysfunction in the development of anti-melanoma differentiation-associated gene 5 (MDA5) dermatomyositis (DM). METHODS: Thirty anti-MDA5 DM patients were enrolled and compared with patients with polymyositis (PM) (n=10) and healthy controls (n=20). The concentrations of soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), endothelin-1 (ET-1) and von Willebrand factor (vWF) as well as interferon-alpha (IFN-α) and Galcetin-9 in the peripheral blood were tested by enzyme-linked immunosorbent assay (ELISA). RESULTS: Plasma levels of sICAM-1, sVCAM-1, ET-1 and vWF were higher in the anti-MDA5 DM patients than in either the healthy controls or the PM patients. In the anti-MDA5 DM cohort, the ET-1 and vWF levels were significantly lower in the cases without cutaneous ulcers and ILD than the other cases. There was a strong positive relationship between the concentrations of ET-1 and Galectin-9 in the anti-MDA5 DM group. CONCLUSIONS: Our data suggest that endothelial dysfunction may be involved in the development of anti-MDA5 DM.

Rituximab in the Treatment of Interstitial Lung Diseases Related to Anti-Melanoma Differentiation-Associated Gene 5 Dermatomyositis: A Systematic Review.

Objective: The effectiveness of rituximab in anti-melanoma differentiation-associated gene 5 (MDA5) dermatomyositis (DM) with interstitial lung disease (ILD) has been explored only in isolated case reports and small series. This paper aims to review the current evidence regarding rituximab (RTX) use in the treatment of ILD related to anti-MDA5 DM (anti-MDA5 DM-ILD). Methods: We conducted a review by searching PubMed, Web of Science, Embase, and Cochrane for articles with information on patients with anti-MDA5 DM and RTX treatment, published until August 2021, in English language. The selected studies listed variation in chest high-resolution computed tomography (HRCT) and/or pulmonary function test (PFT) as a primary outcome, in patients with anti-MDA5 DM-related ILD after using RTX. Results: Of the 145 potentially eligible articles, 17 were selected. The information gathered from a total of 35 patients with anti-MDA5 DM-ILD was reviewed, including 13 men and 22 women. Patient age at onset was 47.60 ± 13.72 years old. A total of 11.43% (4/35) of the patients were found to have chronic ILD (C-ILD) and 88.57% (31/30) exhibited rapidly progressive ILD (RP-ILD). Most patients (29/30) had typical DM rashes. Prior to RTX administration, the majority of patients (27/35) were treated with medium- or high-dose glucocorticoids and at least one additional immunotherapeutic agent. With regard to RTX efficacy for ILD in anti-MDA5 DM, 71.43% (25/35) of the patients responded to treatment. Skin rash also improved in more than half of the patients after RTX treatment. The most common side effects were infections, reported by 37.14% (13/35) of the patients after using RTX. Conclusion: As a CD20 targeting drug, RTX is a promising therapeutic tool for anti-MDA5 DM-ILD, although the risk of infections should be considered before treatment. Further prospective controlled studies are required to evaluate the optimal RTX treatment regimen. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021289714, identifier CRD42021289714.