RESUMEN

OBJECTIVES: Evaluation of disease activity in systemic lupus erythematosus (SLE) nephritis is a challenge, and repeated renal biopsies are usually needed in order to confirm a suspicion of flare. In a previous cross-sectional study, we reported that serum soluble form of the interleukin-7 receptor (sIL7R) levels is strongly associated with nephritis in SLE patients. In the present study, we wanted to confirm the association between changes in serum sIL7R concentrations and renal disease activity in a large longitudinal cohort of SLE nephritis patients. METHODS: Sera were harvested longitudinally in 105 SLE nephritis patients. Serum sIL7R cut-off value for the detection of SLE nephritis activity was determined as the mean sIL7R concentration in non-nephritis SLE patients + 2 SDs using data collected in our previous study. Patients with glomerular filtration rate (GFR) <60 mL/min/1.73 m(2) (n=17) were excluded from the study due to persistently elevated serum sIL7R values. RESULTS: Serum sIL7R concentrations above the renal cut-off value were observed in 25 (out of 88) patients with a normal GFR. These patients had significantly higher serum double-stranded DNA (dsDNA) Ab and urinary protein to creatinine (UPC) ratio. Strikingly, 12 of them developed a renal British Isles Lupus Assessment Group index (BILAG) A within the next 3 months, while this was only the case in four out of the 63 other patients (p<0.0001). The test had 75.0% sensitivity and 81.9% specificity for the detection of a renal BILAG A. Combination of serum sIL7R with any of the classical tests (anti-dsDNA Ab titres, UPC ratio, serum C3) resulted in an increased specificity for the detection of a renal flare. Administration of immunosuppressive therapy resulted in a significant decrease in serum sIL7R concentrations. CONCLUSIONS: Serum sIL7R is a sensitive and specific marker of renal disease activity in SLE. Elevated serum sIL7R values in SLE patients are associated with or predict the occurrence of an SLE nephritis flare.

RESUMEN

OBJECTIVE: Synovitis is a common feature of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), but the pattern of joint involvement differs in each disease. This study was undertaken to investigate the global gene expression profiles in synovial biopsy tissue from the swollen knees of untreated SLE patients (n = 6), RA patients (n = 7), and osteoarthritis (OA) patients (n = 6). METHODS: Synovial biopsy samples were obtained from the affected knees of patients in the 3 groups by needle arthroscopy. Half of the material was used for extraction of total RNA, amplification of complementary RNA, and high-density oligonucleotide spotted hybridization arrays. On the remaining tissue samples, real-time reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemical experiments were performed to confirm the microarray data. RESULTS: SLE synovial biopsy tissue displayed a significant down-regulation of genes involved in extracellular matrix (ECM) homeostasis and a significant up-regulation of interferon-inducible (IFI) genes. Real-time RT-PCR experiments confirmed the up-regulation of selected IFI genes (IFI27, IFI44, and IFI44L) in the SLE synovial tissue. Immunohistochemical analyses showed that 3 molecules involved in ECM regulation, chondroitin sulfate proteoglycan 2, latent transforming growth factor beta binding protein 2, and fibroblast activation protein alpha, were significantly down-regulated in SLE synovium. In contrast, immunostaining for IFI27, Toll-like receptor 4, and STAT-1 resulted in higher quantitative scores in SLE synovial tissue, which could be attributed to the fact that the RA samples had a large population of inflammatory cell infiltrates that were negative for these markers. CONCLUSION: Arthritis in SLE has a very distinct molecular signature as compared with that in OA and RA, characterized by up-regulation of IFI genes and down-regulation of genes involved in ECM homeostasis.

Asunto(s)

Perfilación de la Expresión Génica , Lupus Eritematoso Sistémico/genética , Lupus Eritematoso Sistémico/metabolismo , Membrana Sinovial/metabolismo , Adulto , Anciano , Antígenos/genética , Antígenos/metabolismo , Antígenos de Neoplasias/genética , Antígenos de Neoplasias/metabolismo , Artritis Reumatoide/genética , Artritis Reumatoide/metabolismo , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Biopsia , Proteínas del Citoesqueleto/genética , Proteínas del Citoesqueleto/metabolismo , Regulación hacia Abajo , Endopeptidasas , Femenino , Gelatinasas , Humanos , Proteínas de Unión a TGF-beta Latente/genética , Proteínas de Unión a TGF-beta Latente/metabolismo , Masculino , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Persona de Mediana Edad , Análisis de Secuencia por Matrices de Oligonucleótidos , Osteoartritis de la Rodilla/genética , Osteoartritis de la Rodilla/metabolismo , Serina Endopeptidasas/genética , Serina Endopeptidasas/metabolismo , Membrana Sinovial/patología , Regulación hacia Arriba , Versicanos/genética , Versicanos/metabolismo