Interferon‐regulated chemokines as biomarkers of systemic lupus erythematosus disease activity: A validation study

Abstract

Objective. Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by unpredictable flares of disease activity and irreversible damage to multiple organ systems. An earlier study showed that SLE patients carrying an interferon (IFN) gene expression signature in blood have elevated serum levels of IFN-regulated chemokines. These chemokines were associated with more-severe and active disease and showed promise as SLE disease activity biomarkers. This study was designed to validate IFN-regulated chemokines as biomarkers of SLE disease activity in 267 SLE patients followed up longitudinally.Methods. To validate the potential utility of serum chemokine levels as biomarkers of disease activity, we measured serum levels of CXCL10 (IFN␥-inducible 10-kd protein), CCL2 (monocyte chemotactic protein 1), and CCL19 (macrophage inflammatory protein 3␤) in an independent cohort of 267 SLE patients followed up longitudinally over 1 year (1,166 total clinic visits).Results. Serum chemokine levels correlated with lupus activity at the current visit (P ‫؍‬ 2 ؋ 10 ؊10 ), rising at the time of SLE flare (P ‫؍‬ 2 ؋ 10 ؊3 ) and decreasing as disease remitted (P ‫؍‬ 1 ؋ 10 ؊3 ); they also performed better than the currently available laboratory tests. Chemokine levels measured at a single baseline visit in patients with a Systemic Lupus Erythematosus Disease Activity Index of <4 were predictive of lupus flare over the ensuing year (P ‫؍‬ 1 ؋ 10 ؊4 ).Conclusion. Monitoring serum chemokine levels in SLE may improve the assessment of current disease activity, the prediction of future disease flares, and the overall clinical decision-making.Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease defined by autoantibodies to nuclear components, immune complex deposition, and systemic vasculitis (1). Many organ systems are targeted, including the skin, joints, blood cells, kidneys, and nervous system. The disease affects 0.1% of the US population, with a striking 9:1 preponderance in women. The factors that contribute to the onset and progression of SLE are not well understood; however, genetic, environmental, and hormonal factors are likely to be important. SLE disease activity can be difficult to monitor, and flares are unpredictable, both in frequency and in severity. Certain clinical laboratory tests, including antidouble-stranded DNA (anti-dsDNA) antibody titers, complement factor levels, and the erythrocyte sedimen-

Protein microarray analysis reveals BAFF-binding autoantibodies in systemic lupus erythematosus

“…We found that BAFF reactivity was linked to IFN signature in the ABCoN cohort, and there was also partial overlap in the clinical and serum protein correlates that have previously been described for IFN signature, including elevated levels of anti-dsDNA and anti-La autoantibodies and elevated levels of proinflammatory chemokines (18,41,43). While our observations were based on a limited number of samples, these results suggest that BAFF reactivity may be one facet of a more severe SLE disease state, with at least partial overlap with increased inflammatory pathology associated with an elevated IFN signature.…”

CCL19 as a Chemokine Risk Factor for Posttreatment Lyme Disease Syndrome: a Prospective Clinical Cohort Study

“…Consistent with this, in the mouse model of Lyme disease, CCL19 mRNA expression is increased in the lymph nodes of acutely infected mice (33). Elevated levels of CCL19 have also been observed during states of immune-mediated inflammation, including HIV infection, systemic lupus erythematosus, and rheumatoid arthritis (34)(35)(36)(37). The origin of persistent CCL19 levels among participants with PTLDS is less clear, as patients do not display signs of ongoing immune-mediated processes, such as joint synovitis.…”

Interplay of Cytokines and Chemokines in the Pathogenesis of Systemic Lupus Erythematosus

“…Our result is restricted with the study of (Lit et al, 2006) and (Bauer et al, 2009). They have showed that CCL-2 and CXCL 10 were higher in SLE patients and plasma IL-18 concentration showed strong positive correlation with inflammatory chemokines; CXCL 10 and may be better indicators to assess the current disease activity, prediction of future disease flares and overall clinical decision-making.…”

“…Also, a good association between CXCL 10 and ESR in SLE may suggest Th1 chemokine activity in the disease which may have important roles in leukocyte homing, in the perpetuation of inflammation and concomitant tissue damage (Lee et al, 2009). Parallel to the positive correlation of plasma IL-18 with IP-10 ( Bauer et al, 2009), in the present study, strong positive correlations were obtained between some of the cytokines and chemokines; the level of IFN-γ was positively correlated with CXCL 10, the level of IL-6 was positively associated with CCL 5 and the level of IL-12 was also positively linked with the level of CXCL 10 in SLE patients. These correlation may suggests that increase level of IFN-γ may be due to excessive accumulation of neutrophils at the inflammatory site and increased production of CXCL 10 in SLE patients (Gasperini et al, 1999).…”