RESUMO
The last 2 decades have witnessed the discovery and characterization of a new family of cytokines with immunological characteristics similar to those described for type I interferons, type III or lambda interferons. Unraveling the molecular mechanisms underlying each type of interferon has allowed us to understand how some autoimmune diseases can be considered as interferonopathies. Under normal conditions, type III interferons play a key role in the defense against viruses by modulating the functioning of several types of innate and adaptive immune cells. These effects include upregulation of major histocompatibility complex molecules by myeloid dendritic cells, increased functioning of pattern recognition receptors by plasmacytoid dendritic cells, decreased activity of regulatory T cells, enhanced production of antibodies by plasmatic cells and increased expression of chemokines and adhesion molecules by leukocytes and endothelial cells. Notably, all these mechanisms have been described to boost autoimmunity, and type III interferons pathway activation has been related to the pathogenesis of autoimmune conditions such as systemic lupus erythematosus, systemic sclerosis and Sjögren's syndrome. This review provides an overview of the current evidence on the contribution of type III interferons in the pathogenesis of rheumatic autoimmune diseases in humans.
Assuntos
Doenças Autoimunes/imunologia , Interferons/imunologia , Doenças Reumáticas/imunologia , Autoimunidade , Citocinas/imunologia , Humanos , Inflamação , Interferon Tipo I/imunologia , Interferons/genética , Interferons/metabolismo , Especificidade de Órgãos , Transdução de Sinais/imunologia , Interferon lambdaRESUMO
OBJECTIVE: To assess whether anti-Ro/SSA antibodies are associated with cardiac valve disease in lupus. METHODS: A single-center, medical chart review was performed. Lupus patients were divided according to its anti-Ro/SSA status and subgroups were compared for valvular abnormalities and other characteristics. Dependence of anti-Ro/SSA reactivity to anti-Ro52/TRIM21 antibodies was also evaluated. RESULTS: Eighty-nine lupus patients were analyzed. The most common valvular abnormalities were tricuspid (60%), mitral (41%) and pulmonary (14%) regurgitation. Thirty-six patients were positive and 53 negative for anti-Ro/SSA antibodies. In patients positive to anti-Ro/SSA, a difference was noted for anti-dsDNA (67 versus 45%; p = 0.04) and anti-La/SSB (19 versus 2%; p = 0.004) antibodies. An association between anti-Ro/SSA antibodies and severe mitral regurgitation was observed; indeed, 4/15 patients with anti-Ro/SSA and mitral regurgitation had severe forms of valvulopathy as compared to only 1/22 patients with mitral regurgitation but negative to such antibody (27 versus 5%; p = 0.02). Anti-Ro/SSA antibodies significantly elevated the risk of severe mitral regurgitation (OR = 5). Anti-Ro52/TRIM21 levels (103 ± 29 versus 42 ± 43 U/mL; p = 0.03) and anti-Ro52/TRIM21: anti-Ro/SSA ratios (0.88 ± 0.02 versus 0.35 ± 0.37; p = 0.03) were higher in patients with mitral valve regurgitation than in those with no valvulopathy. CONCLUSION: Anti-Ro/SSA antibodies, mainly against Ro52/TRIM21 antigens, may be pathologically involved in lupus-associated mitral valve regurgitation.