Autoreactive B cell responses targeting nuclear antigens in systemic sclerosis: Implications for disease pathogenesis

Biomarkers in Systemic Sclerosis: An Overview

“…The SSc vascular damage is characterized by the presence of a characteristic processes with a vasomotor instability with an imbalance of vasoactive factors: overproduction of vasoconstrictors (ET-1) and underproduction of vasodilators (NO and prostacyclin) [6][7][8][9][10][11][12][13][22][23][24][25][106][107][108][109]. The free radical nitric oxide (NO) is a potent vasodilator and is synthesized from L-arginine by NO synthase (NOS) [10][11][12][13][14][15][16][17][18][19][22][23][24][25][40][41][42][43][44][45][46][47][48][106][107][108][109][110][111][112][113]. Endothelial isoforms of NOS (eNOS or NOS 3) has been identified with a constitutive expression, other isoforms are shown...…”

“…Endothelial isoforms of NOS (eNOS or NOS 3) has been identified with a constitutive expression, other isoforms are shown in other cell types. Furthermore, an inducible expression (iNOS or NOS 2) in response to a variety of stimuli is possible, with NO-mediated signalling apparent in the skin [10][11][12][13][14][15][16][17][18][19][40][41][42][43][44][45][46][47][48][106][107][108][109][110][111][112][113]. Several studies reported that NO have a biphasic effect in physiological and pathological conditions, being both beneficial and detrimental depending on the concentration and local environment [10][11][12][13][14][15][16][17][18][19][40][41][42][43][44][45][46][47][48].…”

“…Furthermore, an inducible expression (iNOS or NOS 2) in response to a variety of stimuli is possible, with NO-mediated signalling apparent in the skin [10][11][12][13][14][15][16][17][18][19][40][41][42][43][44][45][46][47][48][106][107][108][109][110][111][112][113]. Several studies reported that NO have a biphasic effect in physiological and pathological conditions, being both beneficial and detrimental depending on the concentration and local environment [10][11][12][13][14][15][16][17][18][19][40][41][42][43][44][45][46][47][48]. Recently observation proposed the regulation of NO by endogenous levels of the NOS inhibitor asymmetric dimethylarginine (ADMA) [10]…”

“…The pathogenesis of SSc is complex and not yet completely understood, however the events involved in SSc pathogenesis can be schematically summarized in three main phases: (a) vascular damage, mainly of microcirculation; (b) immune system activation/autoimmunity/inflammation and (c) fibrosis [4][5][6][7][8][9][10]. Fibrosis of the skin and internal organs may be considered the main clinical hallmark of the disease and it is due to fibroblasts activation and dysfunction with the acquisition of a "myofibroblast phenotype" [1,2,[11][12][13][14][15][16][17][18]. Skin manifestations can be recognized and studied by using the modified Rodnan skin score (mRss), the validated method for assessing the severity of skin involvement in SSc and distinguishing the different subsets of skin involvement in SSc [6][7][8][9][10].…”

“…Antinuclear antibodies (ANA) are present in more than 90% of SSc patients, along with anticentromere, anti-Th/To, and anti-topoisomerase I antibodies, which are considered the classic biomarkers present in 60% of SSc patients and help to define precise clinical classifications [4,7,[29][30][31][32][33][34][35][36][37]. Other autoantibodies, such as those directed against the endothelium or fibroblasts, against angiotensin II type 1 receptor, endothelin-1 type A receptor, platelet-derived growth factor receptor (anti-PDGFR), and extracellular matrix (ECM) proteins [16][17][18][19][20][38][39][40][41][42][43][44][45] are also found in SSc patients. More complex autoantibody systems against G-protein-coupled receptors, growth factors, and respective receptors have also been described in SSc [21,[45][46][47][48][49].…”