Systemic sclerosis (SSc) is a complex rheumatologic autoimmune disease in which inflammation, fibrosis, and vasculopathy share several pathogenic pathways that lead to skin and internal organ damage. Recent findings regarding the participation and interaction of the innate and acquired immune system have led to a better understanding of the pathogenesis of the disease and to the identification of new therapeutic targets, many of which have been tested in preclinical and clinical trials with varying results. In this manuscript, we review the state of the art of the pathogenesis of this disease and discuss the main therapeutic targets related to each pathogenic mechanism that have been discovered so far.

No abstract

Fibrosing diseases are causes of morbidity and mortality around the world, and they are characterized by excessive extracellular matrix (ECM) accumulation. The bHLH transcription factor scleraxis (SCX) regulates the synthesis of ECM proteins in heart fibrosis. SCX expression was evaluated in lung fibroblasts and tissue derived from fibrotic disease patients and healthy controls. We also measured SCX in sera from 57 healthy controls, and 56 Idiopathic Pulmonary Fibrosis (IPF), 40 Hypersensitivity Pneumonitis (HP), and 100 Systemic Sclerosis (SSc) patients. We report high SCX expression in fibroblasts and tissue from IPF patients versus controls. High SCX-serum levels were observed in IPF (0.663 ± 0.559 ng/mL, p < 0.01) and SSc (0.611 ± 0.296 ng/mL, p < 0.001), versus controls (0.351 ± 0.207 ng/mL) and HP (0.323 ± 0.323 ng/mL). Serum levels of the SCX heterodimerization partner, TCF3, did not associate with fibrotic illness. IPF patients with severely affected respiratory capacities and late-stage SSc patients presenting anti-topoisomerase I antibodies and interstitial lung disease showed the highest SCX-serum levels. SCX gain-of-function induced the expression of alpha-smooth muscle actin (α-SMA/ACTA2) in fibroblasts when co-overexpressed with TCF3. As late and severe stages of the fibrotic processes correlated with high circulating SCX, we postulate it as a candidate biomarker of fibrosis and a potential therapeutic target.

Background The Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán is a teaching hospital which was converted into a Coronavirus disease 2019 (COVID-19) designated hospital on mid-March 2020. In Mexico City, the COVID-19 peak started in mid-April 2020. A considerable proportion of those diagnosed with SARS-CoV-2 infection were treated by ambulatory care. We aimed to describe the clinical characteristics at diagnosis of ambulatory patients diagnosed with COVID-19, their willingness to donate plasma and their clinical outcomes at one month of the follow-up call program implementation. Methods A call strategy follow-up program (FUP) was established on April 19, 2020. All ambulatory patients received at least 3 calls every 48–72 hours, followed by 2 weekly calls. A team of voluntary medical students, general practitioners, fellows, and medical specialists was assembled for this purpose. Signs of alarm (fever &gt;72 hours, shortness of breath, respiratory insufficiency) and other clinical signs were collected on every call. Willingness to donate plasma and possibility of a correct home isolation were also addressed. Results From April 19 to May 18, 2020, a total of 360 patients tested positive for SARS-CoV2, of whom 350 were followed. Their median age was 44 years (33–51), and 55% were female. 145 (41%) had completed all FUP calls and 194 (55%) referred to be asymptomatic in their last call. We identified 8 patients with signs of alarm during the calls, and 2 of them required hospitalization. During the FUP, 66% referred fatigue that limited their activities, 56% anosmia or dysgeusia, 32% headache, and 22% diarrhea. 90% were capable to properly isolate in their homes. Willingness to donate plasma was assessed in 89 patients, of whom, 75 (84%) manifested their willingness to donate. Conclusion Ambulatory follow-up is feasible and effective to identify those in need of hospitalization. Remarkably, half of the ambulatory patients had no comorbidities and presented anosmia/dysgeusia as the most frequent symptoms during follow-up. Willingness to donate plasma was high in this cohort. Disclosures All Authors: No reported disclosures