During the COVID-19 pandemic, we detected a new immunofluorescence (IF) pattern in serum autoantibody (autoAb) screening of laboratory-confirmed COVID-19 patients. The IF pattern was composed of liver and gastric mucosa staining on rat kidney/liver/stomach sections. We describe 12 patients positive for the cross-reactive Ab, compared to a negative group of 43 hospitalized COVID-19 patients, finding association with either neurologic or thrombotic complications. In sequential pre- and post-COVID-19 serum samples, we confirmed autoAb seroconversion. Our data indicate that autoAb screening in COVID-19 patients may be easily performed by IF and alert for auto-reactive mediated complications such as thrombotic or neurologic events.
Monocyte-derived macrophages contribute to pathogenesis in inflammatory diseases and their effector functions greatly depend on the prevailing extracellular milieu. Whereas M-CSF primes macrophages for acquisition of an anti-inflammatory profile, GM-CSF drives the generation of T cell-stimulatory and pro-inflammatory macrophages. Liver X Receptors (LXRα and LXRβ) are nuclear receptors that control cholesterol metabolism and regulate differentiation of tissue-resident macrophages. Macrophages from rheumatoid arthritis and other inflammatory pathologies exhibit an enriched LXR pathway, and recent reports have shown that LXR activation raises pro-inflammatory effects and impairs the acquisition of the anti-Inflammatory profile of M-CSF-dependent monocyte-derived macrophages (M-MØ). We now report that LXR inhibition prompts the acquisition of an anti-inflammatory gene and functional profile of macrophages generated within a pathological environment (synovial fluid from Rheumatoid Arthritis patients) as well as during the GM-CSF-dependent differentiation of human monocyte-derived macrophages (GM-MØ). Mechanistically, inhibition of LXR results in macrophages with higher expression of the v-Maf Avian Musculoaponeurotic Fibrosarcoma Oncogene Homolog B (MAFB) transcription factor, which governs the macrophage anti-inflammatory profile, as well as over-expression of MAFB-regulated genes. Indeed, gene silencing experiments on human macrophages evidenced that MAFB is required for the LXR inhibitor to enhance the anti-inflammatory nature of human macrophages. As a whole, our results demonstrate that LXR inhibition prompts the acquisition of an anti-inflammatory transcriptional and functional profile of human macrophages in a MAFB-dependent manner, and propose the use of LXR antagonists as potential therapeutic alternatives in macrophage re-programming strategies during inflammatory responses.
Background:An ACR/EULAR task force released new criteria in 2013 to classify patients with systemic sclerosis (SSc).Objectives:This study evaluates the diagnostic performance of these criteria in a multidisciplinary care setting.Methods:Patients with an active follow-up in a Systemic Autoimmune Diseases Unit with a clinical diagnosis of SSc were matched by age and gender with consecutive patients referred to a capillaroscopy clinic. The classification criteria were tested on discrimination and diagnostic accuracy between both groups of patients defined as cases-SSc and controls. Receiver operating characteristic (ROC) curve and the area under the curve (AUC) was calculated for the global score to define the best cut off to classify the patients as having SSc.Results:A total of 130 patients with SSc and 130 matched-controls were included in this analysis, 90% women, with a mean age of 61.5. Main diagnosis for the control groups were primary Raynaud´s phenomenon (34.6%), undiferentiated connective tissue disease (13.1%), and mixed connective tissue disease (9.2%). The 92% and 8% of patients in the SSc-cases and control groups met the 2013 ACR/ EULAR SSc classification criteria respectively. Sensitivity and specificity of the criteria were 81.5% and 93.7%, respectively. The best cut offs for the total score were 8 and 9, and the AUC (95%CI) was 0.962 (0.939-0.985). The individual items with a better discriminatory capacity were abnormal capillaroscopy, telangiectasia and anticentromere antibody positivity.Table 1.Demographic data and ACR/ EULAR SSc classificacion criteria of SSC patients and controls.Cases-SSc, n= 130Controls, n= 130pAge, mean (SD)62.4 (16.0)61.3 (14.8)0.58Female, %90.590.80.92Disease duration from onset of symptoms, mean (SD)7.5 (6.4)7.8 (6.7)0.73% Patients with individual ACR/EULAR 2013 Criteria ItemsSkin thickening15.80.7<0.001Sclerodactily45.56.1<0.001Puffy fingers27.71.5<0.001Digital tip ulcers30.25.3<0.001Fingertip pitting scars18.84.60.001Telangiectasia51.56.1<0.001Abnormal nailfold capillaries79.40.8<0.001Pulmonary Arterial Hypertension16.33.80.001Pulmonary fibrosis18.86.20.002Raynaud´s phenomenon90.766.9<0.001Anticentromere antibody60.718.9<0.001Scl7012.00<0.001Total Score12.5 (4.8)3.4 (2.9)<0.0001Figure 1.ROC curve for global score of the ACR/EULAR2013 SSc classification criteria.Conclusion:The ACR/EULAR 2013 criteria showed good diagnostic properties in this cohort reflecting daily practice. Individual items showing the highest discriminatory capacity were abnormal capillaroscopy, telangiectasia and anticentromere antibody positivity.References:[1]van den Hoogen F, Khanna D, Fransen J, et al. 2013 classification criteria for systemic sclerosis: an American college of rheumatology/European league against rheumatism collaborative initiative. Annals of the Rheumatic Diseases 2013;72:1747-1755.Disclosure of Interests:None declared
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