Systemic Sclerosis Pathogenesis and Emerging Therapies, beyond the Fibroblast

Abstract

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.

HHV-6A Infection and Systemic Sclerosis: Clues of a Possible Association

“…Systemic sclerosis (SSc) is a rare autoimmune disease representing one of the most severe connective tissue pathologies, characterized by vascular obliteration, immunological abnormalities, and excessive extracellular matrix deposition, which causes fibrosis of the skin and of internal organs [1]. The etiopathogenesis of the disease is still unknown; possibly, multiple initial events may trigger the release of different cytokines by inflammatory cells, diffuse microangiopathy, fibroblast activation with abnormal collagen deposition, and subsequent ischemic and fibrotic manifestations [2].…”

The Transcription Factor SCX is a Potential Serum Biomarker of Fibrotic Diseases

“…Furthermore, SSc patients had higher SCX levels than controls, particularly those in late stages of the disease, and with anti-topoisomerase I autoantibodies. As a systemic disease, in SSc, many factors have local and systemic effects on specific tissues that have been associated with severity and progression [44]. Circulating anti-topoisomerase I antibodies (Scl70) have been linked to diffuse disease and the presence and severity of interstitial lung diseases [45].…”

Enzymatic Profile of Blood Plasma in Systemic Sclerosis: Activity of Xanthine Oxidase, Xanthine Dehydrogenase and Superoxide Dismutase

“…В последние годы достигнут определенный прогресс в понимании патогенеза ССД. Если ранее считалось, что в основе заболевания лежат преимущественно фиброзирующие процессы, то в настоящее время доказано, что в его развитии принимают участие несколько механизмов, базирующихся на кооперации иммуно-воспалительных процессов, васкулопатии и фиброза [9,16] Относительно недавно, рядом исследований была выявлена потенциальная роль «окислительного стресса» в патогенезе ССД [11,17]. Было обнаружено, что уровни циркулирующих биомаркеров (малоновый диальдегид, липопротеины низкой плотности, изопростаны, тиолы) активных форм кислорода (АФК), коррелируют с васкулопатией, фиброзом и продукцией аутоантител при ССД [5,8].…”