Abstract
Patients with Systemic sclerosis (SSc) presents immune dysregulation, vasculopathy, and fibrosis of the skin and various internal organs. Pulmonary fibrosis leads to SSc-associated interstitial lung disease (ILD), which is the main cause of morbidity and mortality in SSc. Recently autoimmunity to type V collagen (Col V) has been characterized in idiopathic pulmonary fibrosis and show promise to be related to the development in SSc. Our aim was to evaluate autoimmunity to Col V α1(V) and α2(V) chains and to the antigenic peptides of these Col V chains in early-SSc sera employing lung tissue of SSc-ILD, as antigen source. We found that sera samples from patients with early-SSc were reactive to Col V (41.18%) and presented immunoreactivity for Col5A1(1.049) and Col5A1(1.439) peptides. The IgG isolated from early-SSc patients-anti-Col V positive sera (anti-ColV IgG) was adsorbed with α1(V) chain (anti-ColV IgG/ads-α1(V)) and α2(V) chain (anti-ColV IgG/ads-α2(V)) and biotinylated to evaluate the spectrum of reactivity in SSc-ILD patients lung biopsies by immunofluorescence. The SSc-ILD lung tissue samples immunostained with anti-ColV IgG showed increased green fluorescence in the vascular basement membrane, bronchiolar smooth muscle, and adventitial layer, contrasting with the tenue immunostaining in control lungs. Col V protein expression in these pulmonary compartments immunostained with early-SSc anti-ColV IgG was confirmed by immune colocalization assays with commercial anti-human Col V antibodies. In addition, SSc-ILD lung tissues immunostained with anti-ColV IgG/ads-α1(V) (sample in which Col V α1 chain-specific antibodies were removed) showed decreased green fluorescence compared to anti-ColV IgG and anti-ColV IgG/ads-α2(V). Our data show that autoimmunity to Col V in early-SSc was related to peptides of the α1(V) chain, suggesting that these antibodies could be biomarkers of SSc stages and potential target of immunotherapy with Col V immunogenic peptides.
Highlights
Systemic sclerosis (SSc) is an autoimmune disease that belongs to the family of systemic connective tissue diseases characterized by immune dysregulation, vasculopathy, and fibrosis of the skin and various internal organs
While control lungs have a thin alveolar septa covered by a single layer of alveolar epithelium, characteristic of the normal histoarchitecture of the lung (Figure 2A), SSc-interstitial lung disease (ILD) lung biopsy tissue exhibits a homogeneous septal thickening through inflammation and fibrosis with the maintenance of the lung histoarchitecture, characterizing a nonspecific interstitial pneumonia (NSIP) histologic pattern (Figures 2B, C)
Considering that our data showed the same pattern of immunostaining in the SSc-ILD lung biopsies, incubated with anti-ColV IgG without previous absorption and after absorption with a2(V) chain (anti-ColV IgG/ads-a2(V)), we evaluated a possible correlation, between SSc-ILD lung biopsies immunostaining with anti-Collagen V (Col V) peptides (Table 1) detected in early-SSc sera, who tested positive to anti-Col V
Summary
Systemic sclerosis (SSc) is an autoimmune disease that belongs to the family of systemic connective tissue diseases characterized by immune dysregulation, vasculopathy, and fibrosis of the skin and various internal organs. An excessive expression of proteins in the extracellular matrix (ECM) leads to progressive organ stiffening, which is a hallmark of these diseases. Fibrosis causes SSc-associated interstitial lung disease (ILD), which leads to high morbidity and mortality in SSc [1, 2]. The ECM contains a significant number of “informational” proteins, glycoproteins, proteoglycans and polysaccharides whose interactions with epithelial and endothelial cells play a major role in the control of cell migration, cell adhesion, angiogenesis, and tissue development and repair [3]. One of the commonest features in SSc is a massive exposure of the epithelial/endothelial basement membrane to autoimmune cells. The literature describes marked qualitative and quantitative modifications of the interstitial collagen in SSc patients [4, 5]
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