title: Reassessing the Role of the Active TGF-β1 as a Biomarker in Systemic Sclerosis: Association of Serum Levels with Clinical Manifestations.
abstract: Objective. To determine active TGF-β1 (aTGF-β1) levels in serum, skin, and peripheral blood mononuclear cell (PBMC) culture supernatants and to understand their associations with clinical parameters in systemic sclerosis (SSc) patients.Methods. We evaluated serum samples from 56 SSc patients and 24 healthy controls (HC). In 20 SSc patients, we quantified spontaneous or anti-CD3/CD28 stimulated production of aTGF-β1 by PBMC. The aTGF-β1 levels were measured by ELISA. Skin biopsies were obtained from 13 SSc patients and six HC, and TGFB1 expression was analyzed by RT-PCR.Results. TGF-β1 serum levels were significantly higher in SSc patients than in HC (p< 0.0001). Patients with increased TGF-β1 serum levels were more likely to have diffuse subset (p= 0.02), digital ulcers (p= 0.02), lung fibrosis (p< 0.0001), positive antitopoisomerase I (p= 0.03), and higher modified Rodnan score (p= 0.046). Most of our culture supernatant samples had undetectable levels of TGF-β1. No significant difference in TGFB1 expression was observed in the SSc skin compared with HC skin.Conclusion. Raised active TGF-β1 serum levels and their association with clinical manifestations in scleroderma patients suggest that this cytokine could be a marker of fibrotic and vascular involvement in SSc.
authors.affiliation: Hospital das Clínicas, Universidade Federal de Pernambuco (UFPE), Recife, PE, Brazil; Laboratório de Imunomodulação e Novas Abordagens Terapêuticas, Núcleo de Pesquisa em Inovação Terapêutica Suely Galdino, Recife, PE, Brazil.
authors.forename: Andréa Tavares
authors.identifier: 0000-0003-2345-3363
authors.initials: AT
authors.lastname: Dantas
authors.affiliation: Laboratório de Imunomodulação e Novas Abordagens Terapêuticas, Núcleo de Pesquisa em Inovação Terapêutica Suely Galdino, Recife, PE, Brazil.
authors.forename: Sayonara Maria Calado
authors.initials: SM
authors.lastname: Gonçalves
authors.affiliation: Laboratório de Imunomodulação e Novas Abordagens Terapêuticas, Núcleo de Pesquisa em Inovação Terapêutica Suely Galdino, Recife, PE, Brazil.
authors.forename: Anderson Rodrigues
authors.initials: AR
authors.lastname: de Almeida
authors.affiliation: Hospital das Clínicas, Universidade Federal de Pernambuco (UFPE), Recife, PE, Brazil; Laboratório de Imunomodulação e Novas Abordagens Terapêuticas, Núcleo de Pesquisa em Inovação Terapêutica Suely Galdino, Recife, PE, Brazil.
authors.forename: Rafaela Silva Guimarães
authors.initials: RS
authors.lastname: Gonçalves
authors.affiliation: Laboratório de Imunomodulação e Novas Abordagens Terapêuticas, Núcleo de Pesquisa em Inovação Terapêutica Suely Galdino, Recife, PE, Brazil.
authors.forename: Maria Clara Pinheiro Duarte
authors.initials: MC
authors.lastname: Sampaio
authors.affiliation: Laboratório de Imunomodulação e Novas Abordagens Terapêuticas, Núcleo de Pesquisa em Inovação Terapêutica Suely Galdino, Recife, PE, Brazil.
authors.forename: Kamila de Melo
authors.initials: KM
authors.lastname: Vilar
authors.affiliation: Laboratório de Imunomodulação e Novas Abordagens Terapêuticas, Núcleo de Pesquisa em Inovação Terapêutica Suely Galdino, Recife, PE, Brazil.
authors.forename: Michelly Cristiny
authors.initials: MC
authors.lastname: Pereira
authors.affiliation: Laboratório de Imunomodulação e Novas Abordagens Terapêuticas, Núcleo de Pesquisa em Inovação Terapêutica Suely Galdino, Recife, PE, Brazil.
authors.forename: Moacyr Jesus Barreto de Melo
authors.initials: MJ
authors.lastname: Rêgo
authors.affiliation: Laboratório de Planejamento e Síntese de Fármacos, UFPE, Recife, PE, Brazil.
authors.forename: Ivan da Rocha
authors.initials: ID
authors.lastname: Pitta
authors.affiliation: Hospital das Clínicas, Universidade Federal de Pernambuco (UFPE), Recife, PE, Brazil.
authors.forename: Claudia Diniz Lopes
authors.initials: CD
authors.lastname: Marques
authors.affiliation: Hospital das Clínicas, Universidade Federal de Pernambuco (UFPE), Recife, PE, Brazil.
authors.forename: Angela Luzia Branco Pinto
authors.initials: AL
authors.lastname: Duarte
authors.affiliation: Laboratório de Imunomodulação e Novas Abordagens Terapêuticas, Núcleo de Pesquisa em Inovação Terapêutica Suely Galdino, Recife, PE, Brazil.
authors.forename: Maira Galdino da Rocha
authors.identifier: 0000-0001-5881-0338
authors.initials: MG
authors.lastname: Pitta
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis*; D001706:Biopsy; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012595:Scleroderma, Systemic / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D012867:Skin / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000097:blood* / Q000235:genetics*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D012333:RNA, Messenger; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1