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

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Autor(es):
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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]
Número total de Autores: 12
Afiliação do(s) autor(es):
[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
Número total de Afiliações: 4
Tipo de documento: Artigo Científico
Fonte: FRONTIERS IN IMMUNOLOGY; v. 11, FEB 12 2021.
Citações Web of Science: 0
Resumo

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)

Processo FAPESP: 16/05617-4 - Avaliação do potencial antigênico do colágeno tipo v em esclerose sistêmica
Beneficiário:Ana Paula Pereira Velosa
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 17/11865-3 - Fracionamento bioquímico e avaliação da imunogenicidade do colágeno V em esclerose sistêmica
Beneficiário:Lais Brito
Linha de fomento: Bolsas no Brasil - Iniciação Científica
Processo FAPESP: 18/20403-6 - Marcadores biomoleculares de proliferação e remodelamento em doenças respiratórias agudas e crônicas: promissores alvos terapêuticos
Beneficiário:Vera Luiza Capelozzi
Linha de fomento: Auxílio à Pesquisa - Temático