Incomplete Lupus Erythematosus Patients Research Articles

The Role of Clinical Features and Serum Biomarkers in Identifying Patients with Incomplete Lupus Erythematosus at Higher Risk of Transitioning to Systemic Lupus Erythematosus: Current Perspectives.

Discovery of antinuclear antibodies (ANA) enabled earlier diagnosis of systemic lupus erythematosus (SLE) and other ANA+ connective tissue diseases (CTD). Rheumatologists increasingly encounter high referral volume of ANA+ patients. It has been estimated that only a small percentage of these patients will eventually transition to either SLE or other specified CTD. Incomplete lupus erythematosus (ILE) has been defined as a subset of patients who have some SLE-specific clinical manifestations but do not meet currently accepted classification criteria for SLE. Several studies have been performed with the goal of identifying clinical features, serum and tissue biomarkers that can distinguish those patients with ILE at risk of transitioning to SLE from those who will not. Increased autoantibody diversity, presence of anti-double-stranded DNA (dsDNA) antibodies, high expression of type I and type II interferon (IFN)-gene products, increased serum levels of B-cell-activating factor of the TNF family (BAFF), and certain serum cytokines and complement products have been identified as markers with positive predictive value, particularly when combined together. Once this patient population is better characterized biochemically, clinical trials should be considered with the primary objective to completely halt or slow down the transition from ILE to SLE. Hydroxychloroquine (HCQ) appears to be a promising agent due to its good tolerability and low toxicity profile and open-label studies in ILE patients have already shown its ability to delay the onset of SLE. Other therapeutics, like those targeting abnormal type I and type II IFN-signatures, B-cell specific signaling pathways, complement activation pathways and high BAFF levels should also be evaluated, but the risk to benefit ratio must be carefully determined before they can be considered.

Clinical and Immunologic Profiles in Incomplete Lupus Erythematosus and Improvement with Hydroxychloroquine Treatment.

Objective. The study goals were to evaluate performance of SLE classification criteria, to define patients with incomplete lupus erythematosus (ILE), and to probe for features in these patients that might be useful as indicators of disease status and hydroxychloroquine response. Methods. Patients with ILE (N = 70) and SLE (N = 32) defined by the 1997 American College of Rheumatology criteria were reclassified using the 2012 Systemic Lupus International Collaborating Clinics criteria. Disease activity, patient reported outcomes, and levels of Type I interferon- (IFN-) inducible genes, autoantibodies, and cytokines were measured. Subgroups treated with hydroxychloroquine (HCQ) were compared to patients not on this drug. Results. The classification sets were correlated (R2 = 0.87). ILE patients were older (P = 0.0043) with lower disease activity scores (P < 0.001) and greater dissatisfaction with health status (P = 0.034) than SLE patients. ILE was associated with lower levels of macrophage-derived cytokines and levels of expressed Type I IFN-inducible genes. Treatment of ILE with HCQ was associated with better self-reported health status scores and lower expression levels of Type I IFN-inducible genes than ILE patients not on HCQ. Conclusion. The 2012 SLICC SLE classification criteria will be useful to define ILE in trials. Patients with ILE have better health status and immune profiles when treated with HCQ.

AB0194 HLA DRB1 alleles in incomplete lupus erithematosus

BackgroundSystemic lupus erythematous (SLE) represents a heterogeneous group of patients. Some of them are diagnosed with SLE with mild articular and cutaneous symptoms, while others present with severe organ damage....

Organ damage in high-risk patients with systemic and incomplete lupus syndromes

The objective of this study was to characterize organ damage in lupus patients enrolled in Dallas Regional Autoimmune Disease Registry (DRADR). Retrospective chart review was carried out on 99 patients with four or more diagnostic criteria for systemic lupus erythematosus (SLE) and 15 with less than four of these criteria, who were designated as having incomplete lupus erythematosus (ILE). The majority of patients (84 %) were African American or Hispanic/Latino; mean disease duration was 9.5 years. The mean damage score was 1.57 (range 0-8), and a damage score greater than 0 was present in 64 % of the patients. The ILE group had lower mean damage scores (0.67) than the SLE group (1.67; P = 0.04), explained in part by the shorter disease duration in the ILE patients (4.33 vs. 10.24 years; P = 0.003). The most prevalent damage category was renal, present in 24 % of patients. Malignancies occurred in individuals who were significantly older than those who had renal or peripheral vascular damage (P = 0.0007). The findings confirm clinical impressions that DRADR includes a high-risk lupus population. The ILE patients have less damage but also shorter disease duration, suggesting that this might represent an earlier disease stage. These results are consistent with the hypothesis that ILE patients include a subset that is likely to experience progressive organ damage. Longitudinal study of these patients has significant likelihood of tracking the changes that are correlated with disease progression to SLE.

Interferon signature gene expression is correlated with autoantibody profiles in patients with incomplete lupus syndromes

Interferon (IFN) signature genes have been shown to be expressed highly in peripheral blood of patients with systemic lupus erythematosus (SLE), especially in the presence of active disease. However, the expression of this gene signature in individuals with incomplete forms of lupus and the pathogenic relationship between IFN signature genes and autoantibody production have not been explored fully. In the present study, we examined the gene expression and autoantibody profiles of patients diagnosed with incomplete lupus erythematosus (ILE) to determine correlations of the gene expression signature with autoantibody production. Gene expression analysis was carried out on the 24K Illumina Human Refseq-8 arrays using blood samples from 84 subjects, including patients with SLE (n = 27) or ILE (n = 24), first-degree relatives (FDR) of these patients (n = 22) and non-autoimmune control (NC) individuals (n = 11). Autoantibody expression was measured using standard immunoassays and autoantigen proteomic arrays. Up-regulation of a set of 63 IFN signature genes was seen in 83% of SLE patients and 50% of ILE patients. High levels of IFN gene expression in ILE and SLE showed significant correlations with the expression of a subset of IgG autoantibodies, including chromatin, dsDNA, dsRNA, U1snRNP, Ro/SSA, La/SSB, topoisomerase I and Scl 70, while low IFN levels were correlated with immunoglobulin (Ig)M autoreactivity. These studies suggest that in patients with ILE the IFN gene expression signature may identify a subset of these individuals who are at risk for disease progression. Furthermore, high levels of alpha IFN may promote autoantibody class-switch from IgM to the more pathogenic IgG class.

Clinical outcome and predictors of disease evolution in patients with incomplete lupus erythematosus.

To determine the outcome and identify risk factors for evolution into systemic lupus erythematosus (SLE) in a population of incomplete lupus erythematosus (ILE) patients, we studied the clinical and serologic manifestations in a cohort of 87 ILE patients. ILE patients had at least one but less than four of the American College of Rheumatology (ACR) classification criteria of SLE and did not present distinctive clinical features or meet classification criteria of other connective tissue diseases. The patients that remained with ILE were compared with patients that evolved into SLE and with a cohort of 94 SLE patients. The mean disease duration and follow up of ILE patients were 4.4 +/- 4.1 and 2.2 +/- 2.4 years respectively. Eight patients evolved into SLE, but none presented major organ damage. At baseline, patients that remained with ILE were less likely to have photosensitivity, elevated anti-dsDNA and decreased C3 complement than patients that evolved into SLE. At the end of the study, malar rash and oral ulcerations were also less frequent in the ILE group. Compared with all SLE cases, ILE patients were less likely to have photosensitivity, malar rash, oral ulcers, Raynaud's phenomenon, arthritis, low C3, low C4, positive anti-dsDNA, anti-Sm, anti-RNP, anti-Ro and anti-La antibodies at baseline. Hazard analyses showed that malar rash, oral ulcers, elevated anti-dsDNA and decreased C4 were associated with SLE occurrence. In conclusion, this study suggests that ILE represents a mild spectrum of lupus in which mucocutaneous and serological abnormalities are associated with progression into SLE.