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Autoreactive IgE is prevalent in systemic lupus erythematosus and is associated with increased disease activity and nephritis.

ABSTRACT: The presence of autoantibodies in systemic lupus erythematosus, particularly those of the IgG subclass, have long been associated with disease onset and activity. Here we explored the prevalence of autoreactive IgE in SLE and its relevance to disease in French (n = 79) and United States (US) (n = 117) cohorts with a mean age of 41.5 ± 12.7 and 43.6 ± 15.3 years and disease duration of 13.5 ± 8.5 and 16.6 ± 11.9 years, respectively. Our findings show that approximately 65% of all SLE subjects studied produced IgE antibodies to the seven autoantigens tested. This positivity was increased to almost 83% when only those subjects with active disease were considered. SLE subjects who were positive for anti-dsDNA, -Sm, and -SSB/La -specific IgE showed a highly significant association in the levels of these antibodies with disease activity similar to that of the corresponding IgG's. A strong association of IgE autoantibodies with active nephritis was also found in the combined cohort analysis. A test of the predictive value of autoreactive IgE's and IgGs for disease activity (SLE Disease Activity Index (SLEDAI) ? 4) revealed that the best predictors were dsDNA-specific IgE and IgG, and that the age of an SLE subject influenced this predictive model. The finding argue that the overall levels of IgE autoantibodies, independently or in combination with IgG autoantibodies, may serve as indicators of active disease.

SUBMITTER: Dema B

PROVIDER: S-EPMC3938730 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Autoreactive IgE is prevalent in systemic lupus erythematosus and is associated with increased disease activity and nephritis.

Dema Barbara B Pellefigues Christophe C Hasni Sarfaraz S Gault Nathalie N Jiang Chao C Ricks Tiffany K TK Bonelli Michael M MM Scheffel Jörg J Sacré Karim K Jablonski Mathieu M Gobert Delphine D Papo Thomas T Daugas Eric E Illei Gabor G Charles Nicolas N Rivera Juan J

PloS one 20140228 2

The presence of autoantibodies in systemic lupus erythematosus, particularly those of the IgG subclass, have long been associated with disease onset and activity. Here we explored the prevalence of autoreactive IgE in SLE and its relevance to disease in French (n = 79) and United States (US) (n = 117) cohorts with a mean age of 41.5 ± 12.7 and 43.6 ± 15.3 years and disease duration of 13.5 ± 8.5 and 16.6 ± 11.9 years, respectively. Our findings show that approximately 65% of all SLE subjects stu ...[more]

PMID: 24587356

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Project description:BackgroundLupus nephritis (LN) is a major and severe organ involvement in systemic lupus erythematosus (SLE), whose diagnosis and treatment necessitate to perform kidney biopsy, which is an invasive procedure. Non-invasive urine biomarkers are an active area of investigation to support LN diagnosis and management.ObjectiveTo investigate the role of urinary galectin-3 binding protein (u-Gal-3BP) as a candidate biomarker of renal disease in biopsy proven LN.Patients and methodsLevels of u-Gal-3BP were investigated in a cross-sectional fashion by ELISA in 270 subjects: 86 LN patients, 63 active SLE patients with no kidney involvement, 73 SLE patients with inactive disease and 48 age and sex-matched population-based controls (PBC). Moreover, urine samples were analysed separately by ELISA for additional markers of kidney pathology: neutrophil gelatinase-associated lipocalin (NGAL), osteopontin (OPN), kidney injury molecule-1 (KIM-1) and galectin-3 (Gal-3). The concentrations of all studied molecules were normalized to urine creatinine levels. In 10 patients, post-treatment levels of the biomarkers were measured.ResultsNormalized u-Gal-3BP levels were higher in LN patients compared to the other groups (p < .0001). Comparing different LN classes, u-Gal-3BP levels were higher among patients with proliferative (class III/IV) and membranous (class V) as compared to mesangial (class II) forms (p = .04). In proliferative forms, u-Gal-3BP levels correlated with the activity index in renal biopsies (r = 0.42, p = .004). Moreover, in a subset of 10 patients with repeated kidney biopsy and urine sampling before and after induction treatment, a significant decrease of u-Gal-3BP was observed (p = .03). Among the other markers, KIM-1 was also able to discriminate LN from the other groups, while NGAL, OPN and Gal-3 could not in this cohort.ConclusionGiven its ability to discriminate LN patients from active non-renal and inactive SLE patients, the observed correlation with the activity index in renal biopsies, and its levels declining following treatment, u-Gal-3BP shows promise as a non-invasive urinary biomarker to help detecting and to monitor renal involvement in SLE patients and should be validated in larger cohorts.

Project description:Objective:Systemic lupus erythematosus (SLE) is an immune disease characterized by multiorgan involvement. Neuropsychiatric systemic lupus erythematosus (NPSLE) is one of the most devastating complications of SLE, which lacks efficient diagnostic biomarkers. The recent studies on the anti-GAPDH autoantibodies suggested its potential pathogenic roles in NPSLE. However, the clinical relevance of the anti-GAPDH autoantibodies in patients with SLE is still elusive. In this study, we sought to determine the serum levels of the anti-GAPDH autoantibodies in patients with SLE to investigate the clinical significance of the anti-GAPDH autoantibodies in SLE. Methods:Concentrations of the glyceraldehyde 3-phosphate dehydrogenase autoantibodies (anti-GAPDH autoantibodies) in the serum of 130 SLE patients and 55 healthy individuals were determined by enzyme-linked immunosorbent assay (ELISA). Among the 130 SLE patients, 95 were SLE patients without neuropsychiatric symptoms and 35 had NPSLE. White blood cell (WBC) count, hemoglobin (HB), platelet count (PLT), IgG, IgA, IgM, anti-dsDNA, C3, C4, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), RF, anti-cardiolipin (Acl), ANA, AnuA, anti-SSA, anti-SSB, β2-GPI, urinalysis, and 24 h urine protein were measured by standard laboratory techniques. Systemic lupus erythematosus disease activity index 2000 (SLEDAI-2K) and Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index scores were evaluated accordingly. Results:The serum levels of the anti-GAPDH autoantibodies were significantly elevated in the SLE patients, especially in the patients with NPSLE (P = 0.0011). Elevated serum anti-GAPDH was correlated with increased SLEDAI-2K (P = 0.017), ESR, IgG, and IgM and associated with increased intracranial pressure and incidence of cerebrovascular lesions, but it was protective for seizure disorder incidence. Conclusions:Serum anti-GAPDH autoantibody was increased in both groups of SLE patients with or without neuropsychiatric symptoms and associated with disease severity. It could become an indicator of tissue damages in the brain for the future clinical practice.

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Autoreactive IgE is prevalent in systemic lupus erythematosus and is associated with increased disease activity and nephritis.

Publications

Autoreactive IgE is prevalent in systemic lupus erythematosus and is associated with increased disease activity and nephritis.

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