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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Identification of Autoimmunity to Peptides of Collagen V alpha 1 Chain as Newly Biomarkers of Early Stage of Systemic Sclerosis

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Pereira Velosa, Ana Paula [1] ; Brito, Lais [1] ; de Jesus Queiroz, Zelita Aparecida [1] ; Carrasco, Solange [1] ; de Miranda, Jurandir Tomaz [1] ; Farhat, Cecilia [2] ; Goldenstein-Schainberg, Claudia [1] ; Parra, Edwin Roger [2] ; Oliveira de Andrade, Danieli Castro [1] ; Silva, Pedro Leme [3, 4] ; Capelozzi, Vera Luiza [2] ; Teodoro, Walcy Rosolia [1]
Total Authors: 12
[1] Univ Sao Paulo, Hosp Clin FMUSP, Fac Med, Rheumatol Div, Sao Paulo - Brazil
[2] Univ Sao Paulo, Fac Med, Dept Pathol, Sao Paulo - Brazil
[3] Natl Inst Sci & Technol Regenerat Med, Rio De Janeiro - Brazil
[4] Univ Fed Rio de Janeiro, Ctr Ciencias Saude, Carlos Chagas Filho Biophys Inst, Lab Pulm Invest, Rio De Janeiro - Brazil
Total Affiliations: 4
Document type: Journal article
Source: FRONTIERS IN IMMUNOLOGY; v. 11, FEB 12 2021.
Web of Science Citations: 0

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 alpha 1(V) and alpha 2(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 alpha 1(V) chain (anti-ColV IgG/ads-alpha 1(V)) and alpha 2(V) chain (anti-ColV IgG/ads-alpha 2(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-alpha 1(V) (sample in which Col V alpha 1 chain-specific antibodies were removed) showed decreased green fluorescence compared to anti-ColV IgG and anti-ColV IgG/ads-alpha 2(V). Our data show that autoimmunity to Col V in early-SSc was related to peptides of the alpha 1(V) chain, suggesting that these antibodies could be biomarkers of SSc stages and potential target of immunotherapy with Col V immunogenic peptides. (AU)

Grantee:Ana Paula Pereira Velosa
Support type: Regular Research Grants
FAPESP's process: 17/11865-3 - Biochemical fractionation and evaluation of immunogenicity of collagen V in systemic sclerosis
Grantee:Lais Brito
Support type: Scholarships in Brazil - Scientific Initiation
FAPESP's process: 18/20403-6 - Biomolecular markers of proliferation and remodeling in acute and chronic respiratory diseases: promising therapeutic targets
Grantee:Vera Luiza Capelozzi
Support type: Research Projects - Thematic Grants