Predictors of renal flares and long-term renal outcome in patients with lupus nephritis:results from daily clinical practice

OBJECTIVES: To describe renal outcomes of the lupus nephritis (LN) population of the University Medical Centre Groningen (UMCG) in the Netherlands and to identify predictors for renal flares and long-term renal outcome in daily clinical practice. METHODS: A retrospective analysis of biopsy-proven LN patients with induction and maintenance treatment in the UMCG between 1982 and 2016 was performed. Data were collected at time of diagnosis, after 6 months and every year up to 10 years after diagnosis. Outcome measures were renal relapse (biopsy proven), progression to chronic kidney disease (CKD) stage 3 or 4 and chronic renal replacement therapy. The ability of serum creatinine, proteinuria, creatinine clearance, serum anti-double stranded DNA (anti-dsDNA) antibodies, serum complement 3 (C3) and serum complement 4 (C4), as well as biographic data and histopathological class to predict long-term renal outcome was assessed. RESULTS: Seventy-one patients were included, with median follow-up of 120 months (IQR 48-120 months). During follow-up - up to 10 years - twenty-one (30%) patients experienced at least one relapse. Eleven (15%) patients had CKD stage 3 or 4, of whom eight showed persistent CKD since baseline and two (3%) patients required chronic renal replacement therapy. At baseline, low levels of serum C3 were a significant predictor of renal relapse. Low levels of C3 and C4 at 6 and 12 and proteinuria and high levels of anti-dsDNA at 12 months were significant predictors of renal relapse. At baseline, 6 months and 12 months serum creatinine and creatinine clearance were significant predictors for persistent or newly developed CKD 3 or 4, and need for chronic renal replacement therapy. CONCLUSIONS: Almost one-third of LN patients experience at least one renal relapse during long-term follow up, but only 3% need chronic renal replacement therapy. Our data suggests that early serological remission is associated with a low risk of renal relapse. Decreased renal function at onset and the first year after diagnosis is predictive for decreased renal function at a later stage

From incomplete to complete systemic lupus erythematosus; A review of the predictive serological immune markers

Systemic lupus erythematosus (SLE) is a complex and heterogeneous autoimmune disease. A main challenge faced by clinicians is early identification of SLE, frequently resulting in diagnostic delay. Timely treatment, however, is important to limit disease progression, and prevent organ damage and mortality. Often, patients present with clinical symptoms and immunologic abnormalities suggestive of SLE, while not meeting classification criteria yet. This is referred to as incomplete SLE (iSLE). However, not all these patients will develop SLE. Therefore, there is need for predictive biomarkers that can distinguish patients at high risk of developing SLE, in order to allow early treatment. This article reviews the current literature on immunological changes in patients with stages preceding SLE, focusing on autoantibodies, type-I and -II interferons, and the complement system. We also provide an overview of possible predictive markers for progression to SLE that are applicable in daily clinical practice

Hydroxychloroquine Suppresses Interferon-inducible Genes and B Cell Activating Factor in Patients With Incomplete and New-onset Systemic Lupus Erythematosus

OBJECTIVE: Hydroxychloroquine (HCQ) is commonly used as first-line treatment for systemic lupus erythematosus (SLE). Interferon (IFN)-inducible gene expression, IFN-γ-induced protein 10 (IP-10) and B cell activating factor (BAFF) are early mediators in SLE. The purpose of this study was to analyze the effects of HCQ on these factors. METHODS: Patients with incomplete SLE (iSLE; antinuclear antibody titer ≥ 1:80, symptoms < 5 years, ≥ 1 objectified clinical American College of Rheumatology or SLE International Collaborating Clinics criteria), or new-onset, mild SLE were included when HCQ treatment was started for clinical reasons. Blood samples were taken at start and after 16 weeks. Three SLE-related IFN-inducible genes were measured in whole blood by real-time PCR, and an IFN score was calculated. Serum levels of IP-10 and BAFF were measured using ELISA. RESULTS: In total, 9 patients were included: 7 with iSLE and 2 with new-onset SLE. The median SLE Disease Activity Index (SLEDAI) was 4. After 16 weeks of treatment with HCQ, the expression of IFN-inducible genes decreased in 8 of 9 patients, and the IFN-3 score decreased significantly (P = 0.012). There was a trend towards lower IP-10 levels (P = 0.055), and a significant decrease in BAFF levels (P = 0.023). CONCLUSION: HCQ suppresses IFN score and BAFF levels in patients with iSLE or new-onset SLE, and there is a trend towards lowering IP-10 levels. As these biomarkers are early mediators in SLE, this might support the hypothesis that HCQ could influence disease progression. However, prospective research with a larger sample size and longer follow-up is needed

Scleroderma-like Pattern in Various Rheumatic Diseases reply

We thank Dr. Lambova for her interesting comment1 on our recent article published in The Journal2 We reported that a systemic sclerosis (SSc) or scleroderma-like capillaroscopic pattern is common in patients with Raynaud phenomenon, and can be frequently observed in patients with connective tissue diseases (CTD) other than SSc

Effects of anti-beta 2-glycoprotein 1 antibodies and its association with pregnancy-related morbidity in antiphospholipid syndrome

Antiphospholipid syndrome (APS) is an autoimmune disease characterized by venous, arterial, or small-vessel thrombosis and/or pregnancy-related morbidity, associated with persistent positivity of antiphospholipid antibodies (aPL). Pregnancy-related morbidity in APS patients is characterized by unexplained fetal deaths, premature birth of morphologically normal newborns, and/or consecutive pregnancy losses before the 10th week of gestation. Beta 2-glycoprotein 1 (ß2GP1) is the main antigen recognized by aPL and plays an essential role in the pathogenesis of APS. Antibodies against ß2GP1 (aß2GP1) are involved in damage-generating mechanisms in APS due to their interaction with trophoblasts, decidua, and endothelial cells. aß2GP1 might be used as a prognostic tool for obstetric risk stratification and ß2GP1 could be a target for molecular-targeted treatment to prevent pregnancy morbidity in APS. This review describes these aspects of aß2GP1, including effects on different cellular targets, its association with the severity of obstetric manifestations and the potential of ß2GP1-targeted therapies for APS

Incomplete Systemic Lupus Erythematosus:What Remains After Application of American College of Rheumatology and Systemic Lupus International Collaborating Clinics criteria?

Incomplete systemic lupus (iSLE) is an acknowledged condition of patients with clinical signs of lupus who do not fulfill classification criteria for SLE. Some patients with iSLE have persistent mild disease, but others have serious organ involvement, and up to 55% progress to established SLE. Research on this subject could reveal predictive or diagnostic biomarkers for SLE. Ideally, it would become possible to discern those patients with critical organ involvement or a high risk for progression to SLE. This high-risk group might benefit from early treatment, which would preferably be confirmed in randomized controlled trials. This process would, however, require agreement on a definition of iSLE. The Systemic Lupus International Collaborating Clinics (SLICC) classification criteria was composed in order to diagnose SLE earlier. The present review outlines the clinical characteristics of iSLE after introduction of SLICC criteria and furthermore proposes a definition of iSLE with the aim of discriminating the high-risk group from those with a lower risk