IL-10 EXPRESSION LEVELS AS POTENTIAL BIOMARKER IN WOMEN WITH SLE

Autores

DOI:

https://doi.org/10.25110/arqsaude.v28i2.2024-11246

Palavras-chave:

rs1800896, rs1800871, anti-RO, Brasil

Resumo

Systemic Lupus Erythematosus (SLE) is a multi-systemic autoimmune disease. Its etiology is unclear; however, genetics, environmental, and immunological factors have already been related to the pathogenesis of the disease. There is evidence that cytokines can contribute to SLE, modulating innate and adaptive immune responses. Interleukin-10 (IL-10) is a pleiotropic cytokine previously related to SLE patients and disease activity status. Genetic polymorphisms at the promoter region of IL-10 have been associated with differential protein production, but the findings are conflicting. To assess the potential involvement of polymorphisms -1082 A/G (rs1800896) and -819 A/C (rs1800871) on the susceptibility to disease and clinical features, we identified these variants by TaqMan® SNP assay in a sample of 135 SLE cases and 130 matched controls from an admixed Brazilian population. High IL-10 expression genotypes (-1082 AG or GG) were associated with a protection for SLE (OR 0.317; 95% CI 0.189–0.525; p = 0.001), while no significant results were found for -819 A/C (OR 1.907; 95% CI 0.966–3.921; p = 0.063). Haplotypes of medium or high IL-10 expression were associated with anti-RO positive autoantibodies (p = 0.038), early diagnosis (p = 0.022), and longer fertility time (p = 0.019), possibly predicting a premature but milder disease. These findings indicate that IL-10 polymorphisms influence the susceptibility to SLE in this Brazilian South population and could predict a phenotype characterized by positivity to Anti-RO, premature diagnosis, and longer fertility time.

Biografia do Autor

Maria Luiza Guimarães de Oliveira, Universidade Federal de Santa Catarina

PhD., Universidade Federal de Santa Catarina

Luan Viana Santin, Universidade Federal de Santa Catarina

Sc.M., Universidade Federal de Santa Catarina.

Amanda Carvalho de Barros, Universidade Federal de Santa Catarina

Sc.M., Universidade Federal de Santa Catarina.

Danton Magri, Universidade Federal de Santa Catarina

BSc., Universidade Federal de Santa Catarina.

Manuela Nunes Drehmer, Universidade Federal de Santa Catarina

Sc.M., Universidade Federal de Santa Catarina.

Yara Costa Netto Muniz, Universidade Federal de Santa Catarina

PhD., Universidade Federal de Santa Catarina.

Juliana Dal-Ri Lindenau, Universidade Federal de Santa Catarina

PhD., Universidade Federal de Santa Catarina.

Referências

AKDIS, C. A.; BLASER, K. Mechanisms of interleukin-10-mediated immune suppression. Immunology, v. 103, p. 131–136, 2001.

CAIELLI, S.; WAN, Z.; PASCUAL, V. Annual Review of Immunology Systemic Lupus Erythematosus Pathogenesis: Interferon and Beyond. Annu. Rev. Immunol., v. 41, p. 533–560, 2023.

CHUN, H. Y.; CHUNG, J. W.; KIM, H. A.; YUN, J. M.; JEON, J. Y.; YE, Y. M.; KIM, S. H.; PARK, H. S.; SUH, C. H. Cytokine IL-6 and IL-10 as biomarkers in systemic lupus erythematosus. J Clin Immunol., v. 27, p. 461–466, 2007.

CUTOLO, M.; STRAUB, R. H. Sex steroids and autoimmune rheumatic diseases: state of the art. Nat Rev Rheumatol., v. 16, p. 628–644 2020.

DENG, Y.; TSAO, B. P. Updates in Lupus Genetics. Curr Rheumatol Rep., v.19, n. 68, p. 1-13, 2017.

DORIA, A.; CUTOLO, M.; GHIRARDELLO, A.; ZAMPIERI, S.; VESCOVI, F.; SULLI, A.; GIUSTI, M.; PICCOLI, A.; GRELLA, P.; GAMBARI, P. F. Steroid Hormones and Disease Activity During Pregnancy in Systemic Lupus Erythematosus. Arthritis Rheum., v. 47, p. 202–209, 2002.

ESKDALE, J.; GALLAGHER, G.; VERWEIJ, C. L.; KEIJSERS, V.; WESTENDORP, R. G. J.; HUIZINGA, T. W. J. Interleukin 10 secretion in relation to human IL-10 locus haplotypes. Immunology, v. 95, p. 9465–9470, 1998.

EXCOFFIER, L.; LISCHER, H. E. L. Arlequin suite version 3.5: A new series of programs to perform population genetics analyses under Linux and Windows. Mol Ecol Resour., v. 10, p. 564–567, 2010.

GEGINAT, J.; VASCO, M.; GEROSA, M.; TAS, S.W.; PAGANI, M.; GRASSI, F.; FLAVELL, R. A.; MERONI, P.; ABRIGNANI, S. IL-10 producing regulatory and helper T-cells in systemic lupus erythematosus. Semin Immunol., v. 44, p. 1–9, 2019.

GODSELL, J.; RUDLOFF, I.; KANDANE-RATHNAYAKE, R.; HOI, A.; NOLD, M. F.; MORAND, E. F.; HARRIS, J. CLINICAL ASSOCIATIONS OF IL-10 AND IL-37 in systemic lupus erythematosus. Sci Rep., v. 6, p. 1–10, 2016.

GUO, S. W.; THOMPSON, E. A. Performing the Exact Test of Hardy-Weinberg Proportion for Multiple Alleles. Biometrics, v. 48, p. 361–372, 1992.

HAGIWARA, E.; GOURLEY, M. F.; LEE, S.; KLINMAN, D. M. Disease severity in patients with systemic lupus erythematosus correlates with an increased ratio of interleukin-10: interferon-γ-secreting cells in the peripheral blood. Arthritis Rheum., v. 39, p. 379–385, 1996.

ISHIDA, H.; MUCHAMUEL, T.; SAKAGUCHI, S.; ANDRADE, S.; MENON, S.; HOWARD, M. Continuous Administration of Anti-Interleukin Antibodies Delays Onset of Autoimmunity in NZB/W F1 Mice. J. Exp. Med., v. 179, p. 305–310, 1994.

KIM, J. W.; KIM, H. A.; SUH, C. H.; JUNG, J. Y. Sex hormones affect the pathogenesis and clinical characteristics of systemic lupus erythematosus. Front Med (Lausanne), v. 9, p. 1–15, 2022.

LIU, P.; SONG, J.; SU, H.; LI, L.; LU, N.; YANG, R.; PENG, Z. IL-10 Gene Polymorphisms and Susceptibility to Systemic Lupus Erythematosus: A Meta-Analysis. PLoS One, v. 8, p. 1–11, 2013.

LLORENTE, L.; RICHAUD-PATIN, Y.; GARCÍA-PADILLA, C.; CLARET, E.; JAKEZ-OCAMPO, J.; CARDIEL, M. H.; ALCOCER-VARELA, J.; GRANGEOT-KEROS, L.; ALARCÓN-SEGOVIA, D.; WIJDENES, J.; GALANAUD, P.; EMILIE, D. Clinical and biologic effects of anti-interleukin-10 monoclonal antibody administration in systemic Lupus erythematosus. Arthritis Rheum., v. 43, p. 1790–1800, 2000.

LLORENTE, L.; ZOU, W.; LEVY, Y.; RICHAUD-PATIN, Y.; WIJDENES, J.; ALCOCER-VARELA, J.; MOREL-FOURRIER, B.; BROUET, J.-C.; ALARCON-SEGOVIA, D.; GALANAUD, P.; EMILIE, D. Role of Interleukin 10 in the B Lymphocyte Hyperactivity and Autoantibody Production of Human Systemic Lupus Erythematosus. J. Exp. Med., v. 181, p. 839–844, 1995.

MEILOF, J. F.; VELDHOVEN, C. H. A.; SWAAK, A. J. G.; SMEENK, R. J. T. Production of anti-Ro/SS-A and anti-La/SS-B Autoantibodies is Closely Coordinated in Systemic Lupus Erythematosus and Independent of anti-dsDNA Production. J Autoimmun., v. 10, p. 67–75, 1997.

MILLER, S. A.; DYKES, D. D.; POLESKY, H. F. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res., v. 15, p. 278–282, 1987.

NOVAK, G. V.; MARQUES, M.; BALBI, V.; GORMEZANO, N. W. S.; KOZU, K.; SAKAMOTO, A. P.; PEREIRA, R. M. R.; TERRERI, M. T.; MAGALHÃES, C. S.; GUARIENTO, A.; SALLUM, A. M. E.; MARINI, R.; FERRIANI, V. P. L.; BARBOSA, C. M.; DE CASTRO, T. C. M.; RAMOS, V. C.; BONFÁ, E.; SILVA, C.A. Anti-RO/SSA and anti-La/SSB antibodies: Association with mild lupus manifestations in 645 childhood-onset systemic lupus erythematosus. Autoimmun Rev., v. 16, n. 2, p. 132-135, 2017.

RIGO, D.; WEBER, G.; FRANZ, L.; MIRANDA, G. B. DE, BOFF, E.; PALU, F. H.; CHIELLE, E. O. Correlation between polymorphism (-1082) of interleukin-10 and the injury of development cancer of skin. Brazilian Journal of Oncology, v. 13, n. 45, p. 1-8, 2017.

WESTENDORP, R. G. J. Genetic influence on cytokine production and fatal meningococcal disease. The Lancet, v. 349, p. 170–173, 1997.

SABAT, R.; GRÜTZ, G.; WARSZAWSKA, K.; KIRSCH, S.; WITTE, E.; WOLK, K.; GEGINAT, J. Biology of interleukin-10. Cytokine Growth Factor Rev., v. 21, p. 331–344, 2010.

SIM, J. H.; KIM, H.R.; CHANG, S. H.; KIM, I. J.; LIPSKY, P. E.; LEE, J. Autoregulatory function of interleukin-10-producing pre-naïve B cells is defective in systemic lupus erythematosus. Arthritis Res Ther., v. 17, n. 190, p. 1-15, 2015.

SPITS, H.; MALEFYT, R. DE W. Functional characterization of human IL-10. Int Arch Allergy Immunol., v. 99, p. 8–15, 1992.

TAKAHASHI, S.; FOSSATI, L.; IWAMOTO, M.; MERINO, R.; MOTTA, R.; KOBAYAKAWA, T.; IZUI, S. Imbalance towards Th1 predominance is associated with acceleration of lupus-like autoimmune syndrome in MRL mice. Journal of Clinical Investigation, v. 97, p. 1597–1604, 1996.

TALAAT, R. M.; MOHAMED, S.F.; BASSYOUNI, I. H.; RAOUF, A. A. Th1/Th2/Th17/Treg cytokine imbalance in systemic lupus erythematosus (SLE) patients: Correlation with disease activity. Cytokine, v. 72, p. 146–153, 2015.

TRIFUNOVIĆ, J.; MILLER, L.; DEBELJAK, Ž.; HORVAT, V. Pathologic patterns of interleukin 10 expression - A review. Biochem Med (Zagreb), v. 25, n. 1, p. 36-48, 2015.

TSOKOS, G. C. Autoimmunity and organ damage in systemic lupus erythematosus. Nat Immunol., v. 21, n. 6, p. 605-614, 2020.

TSOKOS, G. C.; LO, M. S.; REIS, P. C.; SULLIVAN, K. E. New insights into the immunopathogenesis of systemic lupus erythematosus. Nat Rev Rheumatol., v. 12, p. 716-730, 2016.

TURNER, D. M.; WILLIAMS, D. M.; SANKARAN, D.; LAZARUS, M.; SINNOTT, P. J.; HUTCHINSON, I. V. An investigation of polymorphism in the interleukin-10 gene promoter. European Journal of Immunogenetics, v. 24, p. 1–8, 1997.

WARD, L. D.; KELLIS, M. HaploReg v4: Systematic mining of putative causal variants, cell types, regulators and target genes for human complex traits and disease. Nucleic Acids Res., v. 44, p. 877–881, 2016.

XIANG, S.; ZHANG, J.; ZHANG, M.; QIAN, S.; WANG, R.; WANG, Y.; XIANG, Y.; DING, X. Imbalance of helper T cell type 1, helper T cell type 2 and associated cytokines in patients with systemic lupus erythematosus: A meta-analysis. Front Pharmacol., v. 13, p. 1–17, 2022.

YIN, Z.; BAHTIYAR, G.; ZHANG, N.; LIU, L.; ZHU, P.; ROBERT, M. E.; MCNIFF, J.; MADAIO, M. P.; CRAFT, J. IL-10 Regulates Murine Lupus. The Journal of Immunology, v. 169, p. 2148–2155, 2002.

ZHAO, N.; CHEN, H. LAN, CHEN, ZHEN, LI, J.; CHEN, ZONG B. IL-10 -592 polymorphism is associated with IL-10 expression and severity of enterovirus 71 infection in Chinese children. Journal of Clinical Virology, v. 95, p. 42–46, 2017.

ZHOU, M.; DING, L.; PENG, H.; WANG, B.; HUANG, F.; XU, W. D.; LI, J. H.; YE, X. R.; PAN, H. F.; YE, D. Q. Association of the interleukin-10 gene polymorphism (-1082A/G) with systemic lupus erythematosus: A meta-analysis. Lupus, v. 22, p. 128–135, 2013.

Downloads

Publicado

11-12-2024

Como Citar

OLIVEIRA, Maria Luiza Guimarães de; SANTIN, Luan Viana; BARROS, Amanda Carvalho de; MAGRI, Danton; DREHMER, Manuela Nunes; MUNIZ, Yara Costa Netto; LINDENAU, Juliana Dal-Ri. IL-10 EXPRESSION LEVELS AS POTENTIAL BIOMARKER IN WOMEN WITH SLE. Arquivos de Ciências da Saúde da UNIPAR, [S. l.], v. 28, n. 2, p. 483–498, 2024. DOI: 10.25110/arqsaude.v28i2.2024-11246. Disponível em: https://revistas.unipar.br/index.php/saude/article/view/11246. Acesso em: 21 dez. 2024.

Edição

Seção

Artigos