BackgroundIdentification of universal biomarkers to predict systemic lupus erythematosus (SLE) flares is challenging due to the heterogeneity of the disease. Several biomarkers have been reported. However, the data of validated biomarkers to use as a predictor for lupus flares show variation. This study aimed to identify the biomarkers that are sensitive and specific to predict lupus flares.MethodsOne hundred and twenty-four SLE patients enrolled in this study and were prospectively followed up. The evaluation of disease activity achieved by the SLE disease activity index (SLEDAI-2K) and clinical SLEDAI (modified SLEDAI). Patients with active SLE were categorized into renal or non-renal flares. Serum cytokines were measured by multiplex bead-based flow cytometry. The correlation and logistic regression analysis were performed.ResultsLevels of IFN-α, MCP-1, IL-6, IL-8, and IL-18 significantly increased in active SLE and correlated with clinical SLEDAI. Complement C3 showed a weakly negative relationship with IFN-α and IL-18. IL-18 showed the highest positive likelihood ratios for active SLE. Multiple logistic regression analysis showed that IL-6, IL-8, and IL-18 significantly increased odds ratio (OR) for active SLE at baseline while complement C3 and IL-18 increased OR for active SLE at 12 weeks. IL-18 and IL-6 yielded higher sensitivity and specificity than anti-dsDNA and C3 to predict active renal and active non-renal, respectively.ConclusionThe heterogeneity of SLE pathogenesis leads to different signaling mechanisms and mediates through several cytokines. The monitoring of cytokines increases the sensitivity and specificity to determine SLE disease activity. IL-18 predicts the risk of active renal SLE while IL-6 and IL-8 predict the risk of active non-renal. The sensitivity and specificity of these cytokines are higher than the anti-dsDNA or C3. We propose to use the serum level of IL-18, IL-6, and IL-8 to monitor SLE disease activity in clinical practice.
Background: Nonscarring alopecia in systemic lupus erythematosus (SLE) is widely recognized, but reports on its clinical, trichoscopic, histopathologic, and direct immunofluorescence (DIF) features are still limited.Objective: To summarize the different clinical patterns, trichoscopic, histopathologic, and DIF features of nonscarring alopecia in SLE and to prove its association with disease activity.Methods: Patients with SLE with and without nonscarring alopecia had full physical/trichoscopic examination and scalp biopsy. Their disease activity scores and laboratory data were evaluated and statistically analyzed.Results: Thirty-two patients with SLE had different patterns of nonscarring alopecia, including mild diffuse alopecia (43.8% [n = 14]), severe diffuse alopecia (15.6% [n = 5]), patchy alopecia (28.1% [n = 9]), and lupus hair (12.5% [n = 4]). The most common trichoscopic findings were arborizing/interconnecting vessels (83% [n = 26]). Histopathologic examination showed interface changes along the dermoepidermal junction (87.5% [n = 28]) and follicular epithelium (40.6% [n = 13]). On DIF, homogeneous granular deposition was detected along the dermoepidermal junction (78.1% [n = 25]) and follicular epithelium (78.1% [n = 25]). When compared with 10 patients with SLE without alopecia, there was a significantly higher SLE Disease Activity Index 2000 score and prevalence of proteinuria ([1 g/d).Limitations: This was a small, cross-sectional, single-center study.Conclusions: Nonscarring alopecia in SLE shows lupus erythematosusespecific changes on histology and DIF. Hair loss in SLE can be considered as an indicator of active disease.
Systemic Lupus Erythematosus (SLE) is an autoimmune disease resulting in autoantibody production, immune complex deposition, and complement activation. The standard biomarkers such as anti-dsDNA and complements (C3 and C4) do not always correlate with active clinical SLE. The heterogeneity of SLE patients may require additional biomarkers to designate disease activity. Ninety SLE patients participated in this study. Evaluation of disease activity was achieved with the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and modified SLEDAI-2K. The measured serum biomarkers were anti-dsDNA, C3, C4, ESR, interleukin-6 (IL-6), and circulating immune complexes (CIC). IL-6, ESR and CIC significantly increased in active clinical SLE. Complement, anti-dsDNA, ESR and CIC correlated with SLEDAI-2K while only anti-dsDNA, CIC, ESR and IL-6 correlated with modified SLEDAI-2K. A combination of biomarkers gave a higher odds ratio (OR) than any single biomarker. A combination of IL-6 or CIC exhibited the highest OR (OR = 7.27, 95%CI (1.99–26.63), p = 0.003) while either complement or anti-dsDNA showed a moderate odds ratio (OR = 3.14, 95%CI (1.16–8.48), p = 0.024) of predicting clinical active SLE. The combination of CIC and IL-6 strongly predicts active clinical SLE. CIC and IL-6 can be used in addition to standard biomarkers to determine SLE activity.
We performed a systematic review and meta-analysis of randomized controlled trials to compare complete remission and adverse events (that is, infection, leukopenia, and gastrointestinal [GI] symptoms) between mycophenolate mofetil (MMF) and cyclophosphamide (CYC) for the treatment of lupus nephritis (LN). We identified trials from MEDLINE using the PubMed and Ovid search engines, and from The Cochrane Central Register of Randomized Controlled Trials. Eligible studies were randomized controlled trials comparing MMF with CYC with 1 of following outcomes: complete remission, complete/partial remission, infection, leukopenia, GI symptoms, serum creatinine, 24-hour urine protein, and urine albumin. Data were independently extracted by 2 reviewers. Five trials with a total of 638 patients were eligible for review. While the MMF group tended to achieve complete remission more frequently than the CYC group, this was not significant (pooled risk ratio [RR], 1.60; 95% confidence interval [CI], 0.87-2.93). Pooling based on the 4 homogeneous trials yielded similar results-that is, no benefit of MMF compared with CYC groups (RR, 1.15; 95% CI, 0.74-1.77). The complete or partial remission rates were also not different (pooled RR, 1.21; 95% CI, 0.97-1.48) among the groups. The adverse events (infection, renal function, and GI symptoms) were not significantly different, except for leukopenia, which was lower in the MMF group. In summary, patients treated with MMF and CYC had similar remission rates, but the MMF group had less frequent leukopenia than the CYC group. Further large-scale trials are needed to confirm these results.
BackgroundPatients with SLE display marked clinical and immunlogical heterogeneity. The purpose of the study was to investigate patterns of serum cytokines in patients with active and stable systemic lupus erythematosus (SLE) and to determine how they relate to clinical phenotype.MethodsSerum levels of 10 cytokines were measured retrospectively in a cohort of patients with SLE and in healthy controls using a high-sensitivity multiplex bead array. Disease activity was determined using the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and British Isles Lupus Assessment Group (BILAG-2004) indices. Logistic regression models were used to determine the association between cytokine levels and active SLE. Principal component analysis (PCA) and cluster analysis was then used to identify subgroups of patients on the basis of cytokine levels.ResultsSerum chemokine (C-X-C motif) ligand 10 (CXCL10) and CXCL13 were significantly higher in patients with SLE compared to healthy controls. Two cytokines (pentraxin-related protein (PTX3) and CXCL10) were significantly higher in patients with active disease after adjustment for potential confounding factors. Measurement of four cytokines (CXCL10, IL-10, IL-21 and PTX3) significantly improved the performance of a model to identify patients with clinically active disease. Cluster analysis revealed that the patients formed 3 distinct groups, characterised by higher levels of interferon alpha (IFNα) and B lymphocyte stimulator (BLyS) (group 1), increased CXCL10 and CXCL13 (group 2) or low levels of cytokines (group 3). Group 2 had significantly lower serum complement and higher anti-double-stranded DNA antibodies and increased prevalence of inflammatory arthritis.ConclusionsMultiplex analysis has identified a serum cytokine signature for active SLE. Within the SLE population distinct cytokine subgroups were identified, with differing clinical and immunological phenotypes that appeared stable over time. Assessment of cytokine profiles may reveal unique insights into disease heterogeneity.Electronic supplementary materialThe online version of this article (10.1186/s13075-018-1666-0) contains supplementary material, which is available to authorized users.
BackgroundThe definition of remission in systemic lupus erythematosus (SLE) remains unclear, especially how background treatment should be interpreted.ObjectiveTo determine preferences of clinicians in treatment of patients in clinical remission from SLE and to assess how previous severity, duration of remission and serology influence changes in treatment.MethodsWe undertook an internet-based survey of clinicians managing patients with SLE. Case scenarios were constructed to reflect different remission states, previous organ involvement, serological abnormalities, duration of remission and current treatment (hydroxychloroquine (HCQ), steroids and/or immunosuppressive (ISS) agents).Results130 clinicians from 30 countries were surveyed. The median (range) duration of practice and number of patients with SLE seen each month was 13 (2–42) years and 30 (2–200), respectively. Management decisions in all scenarios varied with greater caution in treatment reduction with shorter duration of remission, extent of serological abnormalities and previous disease severity. Even with mild disease, normal serology and a 5-year clinical remission, 113 (86.9%) clinicians continue to prescribe HCQ. Persistent abnormal serology in any scenario led to a reluctance to reduce or discontinue medications. Prescribing in remission, particularly of steroids and HCQ, varied significantly according to geographical location.ConclusionsClinicians preferences in withdrawing or reducing treatment in patients with SLE in clinical remission vary considerably. Serological abnormalities, previous disease severity and duration of remission all influence the decision to reduce treatment. It is unusual for clinicians to stop HCQ even after prolonged periods of clinical remission. Any definition(s) of remission needs to take into consideration such evidence on how maintenance treatments are managed.
Background Adult-onset immunodeficiency associated with interferon-γ autoantibody (IGA) is an emerging disease. The majority of patients require both antimicrobial and immunosuppressive treatments. However, anti-CD20 therapy is not fully accessible in a resource-limited setting to date. Background The objectives of this work were to study the efficacy of cyclophosphamide treatment and the role of laboratory biomarkers for disease progression monitoring. Methods A prospective pilot cohort study was conducted among patients with anti-interferon-γ autoantibodies (IGA) who had recurrent infections and required long-term antimicrobial therapy between 2015 and 2018. The patients were categorized into 2 groups: receipt of intravenous cyclophosphamide (IVCY) and receipt of anti-CD20 therapy (RTX). Clinical and laboratory data were determined. Results A total of 17 IGA patients were enrolled. Prolonged fever was the most common manifestation, and the most common infection identified was nontuberculous mycobacterial infections. Both were found in 88.24% of all patients. After completion of IVCY, 9/11 patients achieved complete remission and tended to reach remission faster compared with individuals in the RTX group. The median duration from treatment initiation to remission (interquartile range) was 84 (42–154) days in the IVCY group and 99 (51–202) days in the RTX group. In remission patients, the biomarkers of interest had normalized after treatment, except interferon γ autoantibody titers. There were no differences in adverse events among the 2 groups. Conclusion IVCY may be considered as alternative therapy in this population, especially in resource-limited countries. A comparable clinical outcome to RTX may support its use on a larger scale. However, further study is encouraged.
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