Genetic polymorphisms and surface expression of CTLA-4 and PD-1 on T cells of silica-exposed workers

Autor(es)

Rocha, Michelle C. ^[1] ; Santos, Leonilda M. B. ^[2] ; Bagatin, Ericson ^[3] ; Tervaert, Jan W. Cohen ^[4] ; Damoiseaux, Jan G. M. C. ^[5] ; Lido, Alessandro V. ^[3] ; Longhini, Ana L. ^[2] ; Torello, Cristiane O. ^[1] ; Queiroz, Mary L. S. ^[1]

Afiliação do(s) autor(es)

^[1] State Univ Campinas UNICAMP, FCM, Fac Med Sci, Dept Pharmacol & Hemoctr, BR-13083878 Campinas, SP - Brazil

^[2] State Univ Campinas UNICAMP, Inst Biol, Neuroimmunol Unit, Dept Genet, BR-13083878 Campinas, SP - Brazil

^[3] State Univ Campinas UNICAMP, FCM, Fac Med Sci, Occupat Med Area, Dept Prevent & Social Med, BR-13083878 Campinas, SP - Brazil

^[4] Maastricht Univ, Med Ctr, Div Clin & Expt Immunol, Dept Internal Med, Maastricht - Netherlands

^[5] Maastricht Univ, Med Ctr, Clin Immunol Lab, Maastricht - Netherlands

• Tipo de documento: Artigo Científico
• Fonte: INTERNATIONAL JOURNAL OF HYGIENE AND ENVIRONMENTAL HEALTH; v. 215, n. 6, p. 562-569, NOV 2012.
• Citações Web of Science: 8

Resumo

Exposure to silica dust has been examined as a possible risk factor for autoimmune diseases, including scleroderma, rheumatoid arthritis and systemic lupus erythematosus. Since CTLA-4 {[}CD152] and PD-1 {[}CD279] are important for the maintenance of peripheral tolerance by regulating T cell responsiveness, we evaluated the expression of these molecules on the surface of CD4 and CD8 T cells, as well as single nucleotide polymorphisms (SNP) in CTLA-4 and PDCD1 genes, of 70 silica-exposed workers and 30 non-exposed, age-, ethnically- and sex-matched controls. Expression of CTLA-4 was significantly (P < 0.05) reduced in CD4 T cells of exposed individuals {[}median = 0.1% and interquartile range, IQR 0.0-0.1% (exposed), median = 0.20%, IQR 0.0-0.4% (control)]. Also the expression of PD-1 was significantly (P<0.0001) reduced in both CD4 {[}median = 0.9%, IQR 0.4-2.3% (exposed), median = 5.7%, IQR 1.4-13.3% (control)] and CD8 T cells {[}median = 0.9%, IQR 0.3-1.9% (exposed), median = 5.0%, IQR 3.4-8.9% (control)]. The study of polymorphisms demonstrated a lower frequency of the A allele in the analysis of the PD1.3 SNP in the exposed group, which might be associated with the lower expression of PD-1 on the surface of CD4 T cells. Our findings provide evidence for the association of silica exposure and the maintenance of self-tolerance, i.e., the susceptibility to autoimmune disorders. (C) 2011 Elsevier GmbH. All rights reserved. (AU)

• Processo FAPESP: 01/13823-8 - Alterações imunotoxicológicas e estresse oxidativo de eritrócitos e neutrófilos em trabalhadores expostos à silica
• Beneficiário: Mary Luci de Souza Queiroz
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 07/53901-4 - Investigação da autoimunidade em associação à exposição ocupacional à sílica
• Beneficiário: Michelle Rocha Parise
• Modalidade de apoio: Bolsas no Brasil - Doutorado