RESUMO
Systemic Lupus Erythematosus (SLE) remains a challenging disease to diagnose and follow, as no reliable biomarkers are known to date. We designed a gene expression panel with 40 genes known to play a role in SLE pathogenesis. We found that the combined expression of these genes in SLE T cells can accurately differentiate SLE from healthy individuals and patients with other autoimmune diseases. The accuracy of the test increased further (83%) when only three out of the initial genes (OAS2, CD70 and IL10) were used. A T cell score, calculated from the combined expression levels of these genes, correlated positively with various SLE activity markers in a cross-sectional cohort and in a few patients that were followed prospectively. These data showcase the usefulness of measuring mRNA levels of key molecules in diagnosing and following patients with SLE.
Assuntos
Regulação da Expressão Gênica , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/imunologia , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , 2',5'-Oligoadenilato Sintetase/genética , Adulto , Idoso , Artrite Reumatoide/genética , Artrite Reumatoide/imunologia , Biomarcadores , Ligante CD27/genética , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Interleucina-10/genética , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Lúpus Eritematoso Sistêmico/diagnóstico , Masculino , Pessoa de Meia-Idade , TranscriptomaRESUMO
OBJECTIVE: To quantify the expression of CD44 and variant isoforms CD44v3 and CD44v6 on T cells from patients with systemic lupus erythematosus (SLE), and to assess correlations of the level of expression of these molecules with disease manifestations. METHODS: Information on clinical and demographic characteristics was collected, and blood samples were obtained from 72 patients with SLE and 32 healthy control subjects matched to the patients by sex, race, and age. Expression of CD44 and variants CD44v3 and v6 on T cell subsets was determined by flow cytometry, and Pearson's correlations of their expression levels with clinical variables, SLE Disease Activity Index (SLEDAI) scores, and presence of lupus nephritis were determined. Wilcoxon's rank sum tests and conditional multivariable regression analyses were applied to identify differences in the expression of CD44 between patients with SLE and healthy controls. RESULTS: Expression of CD44 was higher on CD4+ and CD8+ T cells from SLE patients compared with controls (P Assuntos
Biomarcadores
, Marcadores Genéticos
, Receptores de Hialuronatos/genética
, Lúpus Eritematoso Sistêmico/genética
, Lúpus Eritematoso Sistêmico/imunologia
, Linfócitos T/imunologia
, Adulto
, Idoso
, Progressão da Doença
, Feminino
, Expressão Gênica/imunologia
, Variação Genética
, Humanos
, Lúpus Eritematoso Sistêmico/fisiopatologia
, Masculino
, Pessoa de Meia-Idade
, Análise Multivariada
, Análise de Regressão
, Adulto Jovem