Anti-tumor necrosis factor‑α (TNF-α)-induced lupus (ATIL) represents a diagnostic and treatment challenge. Most cases are caused by infliximab and in some cases by etanercept and adalimumab. Symptoms can range from cutaneous manifestations to more rare and serious conditions. Diagnosis requires a temporal relationship between symptoms and positive autoantibody determination. Arthritis and cutaneous symptoms are the most common manifestations accompanied by positive antinuclear antibody (ANA) and anti-double strand DNA (dsDNA) determinations. The etiology of ATILS remains to be definitively established. Several mechanisms have been proposed for anti-TNF-α-induced lupus, including apoptosis, immunosuppression and humoral autoimmunity. Treatment includes discontinuation of anti-TNF‑α agents and in some cases corticosteroids and immunosuppressors. Questions to be answered: (1) Are soluble TNF receptor fusion proteins such as etanercept and anti-TNF chimeric antibodies equally likely to cause ATIL? (2) Can patients with ATIL switch from one anti-TNF‑α antagonist to another? (3) Can the concurrent use of a conventional synthetic disease-modifying antirheumatic drug (csDMARD) like methotrexate or hydroxychloroquine reduce the probability of ATIL?

01 Dec 2020·Journal of NeuroinflammationQ1 · MEDICINE

Tumor necrosis factor inhibition attenuates white matter gliosis after systemic inflammation in preterm fetal sheep

Q1 · MEDICINE

ArticleOA

Author: Dean, Justin M ; Davidson, Joanne O ; Wassink, Guido ; Nott, Fraser ; Galinsky, Robert ; Kelly, Sharmony B ; Bennet, Laura ; Fraser, Mhoyra ; Lear, Christopher A ; Yuill, Caroline ; Gunn, Alistair Jan ; Dhillon, Simerdeep K

AbstractBackgroundIncreased circulating levels of tumor necrosis factor (TNF) are associated with greater risk of impaired neurodevelopment after preterm birth. In this study, we tested the hypothesis that systemic TNF inhibition, using the soluble TNF receptor Etanercept, would attenuate neuroinflammation in preterm fetal sheep exposed to lipopolysaccharide (LPS).MethodsChronically instrumented preterm fetal sheep at 0.7 of gestation were randomly assigned to receive saline (control; n = 7), LPS infusion (100 ng/kg i.v. over 24 h then 250 ng/kg/24 h for 96 h plus 1 μg LPS boluses at 48, 72, and 96 h, to induce inflammation; n = 8) or LPS plus two i.v. infusions of Etanercept (2 doses, 5 mg/kg infused over 30 min, 48 h apart) started immediately before LPS-exposure (n = 8). Sheep were killed 10 days after starting infusions, for histology.ResultsLPS boluses were associated with increased circulating TNF, interleukin (IL)-6 and IL-10, electroencephalogram (EEG) suppression, hypotension, tachycardia, and increased carotid artery perfusion (P < 0.05 vs. control). In the periventricular and intragyral white matter, LPS exposure increased gliosis, TNF-positive cells, total oligodendrocytes, and cell proliferation (P < 0.05 vs control), but did not affect myelin expression or numbers of neurons in the cortex and subcortical regions. Etanercept delayed the rise in circulating IL-6, prolonged the increase in IL-10 (P < 0.05 vs. LPS), and attenuated EEG suppression, hypotension, and tachycardia after LPS boluses. Histologically, Etanercept normalized LPS-induced gliosis, and increase in TNF-positive cells, proliferation, and total oligodendrocytes.ConclusionTNF inhibition markedly attenuated white matter gliosis but did not affect mature oligodendrocytes after prolonged systemic inflammation in preterm fetal sheep. Further studies of long-term brain maturation are now needed.

01 Dec 2017·Arthritis Research & TherapyQ2 · MEDICINE

A longitudinal study of fecal calprotectin and the development of inflammatory bowel disease in ankylosing spondylitis

Q2 · MEDICINE

ArticleOA

Author: Strid, Hans ; Klingberg, Eva ; Öhman, Lena ; Carlsten, Hans ; Forsblad-d'Elia, Helena ; Deminger, Anna ; Ståhl, Arne

BACKGROUNDPatients with ankylosing spondylitis (AS) are at increased risk of developing inflammatory bowel disease (IBD). We aimed to determine the variation in fecal calprotectin in AS over 5 years in relation to disease activity and medication and also to study the incidence of and predictors for development of IBD.METHODSFecal calprotectin was assessed at baseline (n = 204) and at 5-year follow-up (n = 164). The patients answered questionnaires and underwent clinical evaluations. At baseline and at 5-year follow-up, ileocolonoscopy was performed in patients with fecal calprotectin ≥500 mg/kg and ≥200 mg/kg, respectively. The medical records were checked for diagnoses of IBD during the follow-up period.RESULTSFecal calprotectin >50 mg/kg was found in two-thirds of the patients at both study visits. In 80% of the patients, fecal calprotectin changed by <200 mg/kg between the two measuring points. Baseline fecal calprotectin was positively correlated with Ankylosing Spondylitis Disease Activity Score based on C-reactive protein, Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, C-reactive protein, erythrocyte sedimentation rate, and fecal calprotectin at 5-year follow-up. The use of nonsteroidal anti-inflammatory drugs (NSAIDs) was associated with higher fecal calprotectin, and 3-week cessation of NSAIDs resulted in a drop of a median 116 mg/kg in fecal calprotectin. The use of tumor necrosis factor (TNF) blockers was associated with lower fecal calprotectin at both visits, but the users of TNF receptor fusion proteins had significantly higher fecal calprotectin than users of anti-TNF antibodies at 5-year follow-up. The 5-year incidence of Crohn's disease (CD) was 1.5% and was predicted by high fecal calprotectin.CONCLUSIONSFecal calprotectin was elevated in a majority of the patients and was associated with disease activity and medication at both visits. CD developed in 1.5% of the patients with AS, and a high fecal calprotectin was the main predictor thereof. The results support a link between inflammation in the gut and the musculoskeletal system in AS. We propose that fecal calprotectin may be a potential biomarker to identify patients with AS at risk of developing IBD.TRIAL REGISTRATIONClinicalTrials.gov identifier: NCT00858819 . Registered 9 March 2009. Last updated 28 May 2015.

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