No abstract

The improved survival of childhood-onset systemic lupus erythematosus (cSLE) has resulted in longer patients' exposure to disease inflammation, medications and/or comorbid diseases, which can all contribute to the development of organ damage. The aim of this study was to assess the evolution of damage accrual in cSLE patients overtime and investigate for predisposing factors. Disease characteristics and treatment in 47 Northern Greek Caucasian cSLE patients were retrospectively reviewed. The Systemic Lupus International Collaboration Clinics/American College of Rheumatology Damage Index (SDI) was used for damage assessment and the European Consensus Lupus Activity Measurement (ECLAM) to monitor cSLE activity. After a median disease duration of 7.4 years, 17/47 patients (36 %) had developed damage (SDI > 0). The most frequent domains damaged were the ocular (41 %), neuropsychiatric (35 %) and peripheral vascular (35 %) one. Peripheral vascular and neuropsychiatric damage was seen more frequently during the first 5 years of the disease. Longer exposure to azathioprine was associated with higher SDI at the end of follow-up (β = 0.008 for every additional month of use, p = 0.041). The mean annual flare frequency was associated with a shorter time interval until the development of the first damage (hazard's ratio, HR 2.38 for each unit of increase, p = 0.018), while hydroxychloroquine use was associated with longer time interval (HR 0.19, p = 0.007). The lower rates of damage accrual in this study compared to other cohorts might be due to milder disease phenotype in Greek Caucasian cSLE patients, prompt diagnosis and effective disease control. Damage was noticed early in the disease course, and one-third of patients had an SDI > 0 at study completion. Disease flares and a severe disease course leading to prolonged use of immunosuppressives were significant risk factors, while hydroxychloroquine use was protective against cSLE damage accrual.

The discovery of serum biomarkers specific for paediatric lupus nephritis (pLN) will facilitate the non-invasive diagnosis, follow-up and more appropriate use of treatment. The aim of this study was to explore the role of serum high-mobility group box 1 (HMGB1) protein, antibodies against nucleosomes (anti-NCS), complement factor C1q (anti-C1q) and glomerular basement membrane (anti-GBM) in pLN. Serum samples of 42 patients with paediatric systemic lupus erythematosus (pSLE) (22 with pLN and 20 without renal involvement), 15 patients with other autoimmune nephritis (AN) and 26 healthy controls (HCs) were examined using enzyme-linked immunosorbent assay (ELISA). The activity of both pSLE and pLN was assessed by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) tool. The levels of all four biomarkers were significantly higher in pLN compared to AN and to HCs. The anti-NCS, anti-GBM and HMGB1 serum levels were significantly higher in pLN than in pSLE without renal involvement. The anti-C1q and the HMGB1 serum levels were correlated positively with pSLE activity. The HMGB1 serum levels were also correlated positively with pLN activity. These findings suggest that serum anti-NCS, anti-GBM and HMGB1 may serve as biomarkers specific for the presence of nephritis in pSLE. HMGB1 emerged as a useful biomarker for the assessment of pLN and pSLE activity, whereas anti-C1q only of pSLE activity.

Lupus nephritis (LN) is the major determinant of outcome in pediatric systemic lupus erythematosus (pSLE), and its treatment remains a challenge. The aim of this study was to report the experience of our center in treating with rituximab (RTX) SLE patients with severe LN. Four pSLE patients with biopsy-proven LN, who are refractory to conventional immunosuppressive treatment, received four doses of 375-500 mg/m(2) RTX, 2-3 weeks apart. All patients were concurrently receiving corticosteroids (CSs) and mycophenolate mofetil. Patients' clinical and laboratory findings were recorded at RTX initiation, after each infusion and at 3.4 ± 2.1 month intervals thereafter. pSLE activity was assessed using the European Consensus Lupus Activity Measurement (ECLAM), while LN activity using 24-hour urine protein excretion and serum cystatin C. Patients were followed up for 6-21 months (median: 16 months). Full Β-cell depletion was noticed 2-4 weeks after RTX initiation and lasted 4-7 months. All patients achieved complete LN remission 3.5 months (range: 2-4) after RTX initiation, which was retained in 3 patients through the follow-up period. One patient relapsed 15 months after RTX initiation and received one additional RTX dose. ECLAM scores and CSs doses were markedly reduced in all patients, while complement levels were increased. No side effects or infections were observed. In conclusion, RTX is an alternative, safe and efficient treatment for refractory LN.

Background Nephritis is the most common severe manifestation of pediatric Systemic Lupus Erythematosus (pSLE) and the major predictor of poor prognosis. Research for the detection of novel and accurate biomarkers, predictive of the nephritis outcome, is globally in progress. Ethnicity affects the disease outcome but data on purely Caucasian populations are still limited. Objectives The exploration of the role of serum biomarkers, namely anti-nucleosome antibodies (anti-NCS), anti-C1q antibodies (anti-C1q), anti-glomerular basement membrane antibodies (anti-GBM) and high mobility group box 1 (HMGB1) in pSLE nephritis and the association of their levels with pSLE nephritis and pSLE disease activity. Methods Twenty-four patients (16 female) with pSLE nephritis (44 serum samples, 22 in active nephritis) and 21 patients (18 female) with pSLE without nephritis (32 serum samples, 19 in active pSLE) were enrolled in the study. The disease control group included 17 patients with nephritis of other causality (Henoch-Schönlein purpura nephritis, IgA nephropathy, postinfectious glomerulonephritis, membranous glomerulonephritis), who provided equal serum samples. The SLICC renal activity score was applied for assessing pSLE nephritis disease activity and ECLAM for global pSLE disease activity. The biomarkers’ levels were determined by ELISA. Results The pSLE nephritis patients had significantly higher serum levels of anti-NCS [median: 48.89 (IQR: 31.48-80.81) U/ml versus 12.5 (11.5-27.8) U/ml, p<0.001], anti-C1q [22.75 (12.77-56.4) U/ml versus 12.5 (12.5-12.5) U/ml, p<0.001], anti-GBM [3.88 (2.25-6.94) U/ml versus 2.2 (2.2-2.4) U/ml, p=0.002] and HMGB1 [9.9 (5.7-32.23) ng/ml versus 2.5 (2.5-2.5) ng/ml, p<0,001], than the patients with nephritis of other causality. Serum anti-GBM levels were significantly higher in the pSLE nephritis patients compared to the pSLE patients without nephritis [3.88 (2.25-6.94) U/ml versus 2.25 (2.2-2.83) U/ml, p=0.014], while this was not true for the rest of the biomarkers. In the pSLE nephritis patients no correlation was found between serum anti-GBM levels and pSLE nephritis disease activity. Serum anti-NCS and anti-C1q levels were positively correlated with the ECLAM score in the pSLE patients as a whole (p=0.002, rho=0.492 and p=0.007, rho=0.461, respectively). Conclusions In this pure Caucasian Northern Greek pSLE population, high serum anti-GBM levels were found to be associated with the presence of nephritis, but not with the disease activity. Serum anti-GBM, anti-NCS, anti-C1q and HMGB1 may be used to differentiate patients with pSLE nephritis from patients with nephritis of other causality. Furthermore, serum anti-NCS and anti-C1q may be useful for the estimation of pSLE disease activity. References Mok CC. Biomarkers for lupus nephritis: a critical appraisal. J Biomed Biotechnol. 2010;2010:638413. Petri M et al. Systemic lupus international collaborating clinics renal activity/response exercise: development of a renal activity score and renal response index. Arthritis Rheum....