What is the clinical significance of anti-Sm antibodies in systemic lupus erythematosus? A comparison with anti-dsDNA antibodies and C3.

OBJECTIVES: To investigate the clinical value of anti-Sm antibodies in diagnosis and monitoring of systemic lupus erythematosus (SLE) and their ability to predict lupus flares compared with that of anti-dsDNA antibody and complement (C3) assays. METHODS: Autoantibodies against Smith antigen (Sm) and double-stranded DNA (dsDNA) in sera from SLE (n=232), myositis (n=26), systemic sclerosis (n=81), Sjögren's syndrome (n=88), and rheumatoid arthritis patients (n=165) and healthy donors (n=400) were determined by using enzyme-linked immunosorbent assays (both from Euroimmun). New thresholds for both autoantibodies were calculated by receiver operating characteristics (ROC) curve analysis. Cross-sectional, longitudinal and predictive analyses of anti-Sm and disease activity were also performed. RESULTS: Sensitivities of 25.9% for anti-Sm (cut-off: 3.6 relative units/ml) and 30.2% for anti-dsDNA (cut-off 157.4 international units/ml) were obtained at a specificity of 99%. 14.8% of anti-dsDNA-negative patients were positive for anti-Sm, and more than half (51.4%) of anti-dsDNA-positive patients were also positive for anti-Sm. Anti-Sm antibodies were associated with age (p=0.0174), the number of ACR criteria (p=0.0242), the ACR criteria renal (p=0.0350) and neurologic disorder (p=0.0239), the BILAG category constitutional symptoms (p=0.0227), fatigue (p=0.0311) and cross-sectional disease activity (r=0.2519, p=0.0224). Although no correlations with lupus activity were observed in the longitudinal and predictive analysis, a remarkable association was found between anti-Sm and proteinuria. CONCLUSIONS: Anti-Sm antibodies are essential for diagnosis of SLE, especially in anti-dsDNA-negative patients. However, our data suggest that anti-Sm monitoring is only helpful in SLE patients with active lupus nephritis.

Type I interferon as a biomarker in autoimmunity and viral infection: a leukocyte subset-specific analysis unveils hidden diagnostic options.

Interferon alpha and its surrogates, including IP-10 and SIGLEC1, paralleled changes of disease activity in systemic lupus erythematosus (SLE). However, the whole blood interferon signature (WBIFNS)-the current standard for type I IFN assessment in SLE-does not correlate with SLE disease activity in individual patients over time. The underlying causes for this apparent contradiction have not been convincingly demonstrated. Using a multicenter dataset of gene expression data from leukocyte subsets in SLE, we identify distinctive subset-specific contributions to the WBIFNS. In a subsequent analysis, the effects of type I interferon on cellular blood composition in patients with SLE and hepatitis B were also studied over time. We found that type I interferon mediates significant alterations in whole blood composition, including a neutropenia and relative lymphocytosis. Given different effects of type 1 interferon on different leukocyte subsets, these shifts confound measurement of a type 1 interferon signature in whole blood. To minimize and overcome these limitations of the WBIFNS, we suggest to measure IFN-induced transcripts or proteins in a specific leukocyte subset to improve clinical impact of interferon biomarkers. KEY MESSAGES: Myeloid cells contribute more to the WBIFNS in SLE than their lymphocytic counterpart. Very similar leukocyte subsets reveal distinctive IFN signatures. IFN alpha mixes up composition of blood and leads to a preferential neutropenia, yielding relative lymphocytosis.