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

Author(s):Show less -

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]

Affiliation

^[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

• Document type: Journal article
• Source: FRONTIERS IN IMMUNOLOGY; v. 11, FEB 12 2021.
• Web of Science Citations: 0

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 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)

• FAPESP's process: 16/05617-4 - EVALUATION OF ANTIGENIC POTENTIAL OF THE COLLAGEN TYPE V IN SYSTEMIC SCLEROSIS
• 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: promise therapeutic targets
• Grantee: Vera Luiza Capelozzi
• Support type: Research Projects - Thematic Grants