British Isles Lupus Assessment Group Scores Research Articles

Effects of N-acetylcysteine on systemic lupus erythematosus disease activity and its associated complications: a randomized double-blind clinical trial study

BackgroundsN-acetylcysteine (NAC) has broadly been used as an anti-oxidant agent in various types of diseases. This study aimed to assess the effect of NAC on the systemic lupus erythematosus (SLE) disease activity and outcome.MethodsIn this randomized, double-blind clinical trial study, 80 SLE patients were recruited that were classified into two groups: 40 patients received NAC (1800 mg/day; 3 times per day with 8-h intervals) for 3 months and 40 patients as the control group received normal therapies. Laboratory measurements and disease activity based on the British Isles Lupus Assessment Group (BILAG) and SLE Disease Activity Index (SLEDAI) were determined before the initiation of treatment and after the study time period.ResultsA statistically significant decrease in BILAG (P= 0.023) and SLEDAI (P= 0.034) scores after receiving NAC for a 3-month period was observed. BILAG (P= 0.021) and SLEDAI (P= 0.030) scores were significantly lower in NAC-receiving patients compared to the control group after 3 months. The disease activity in each organ based on BILAG score after treatment indicated a significant decrease in the NAC group compared to the baseline level in general (P=0.018), mucocutaneous (P=0.003), neurological (P=0.015), musculoskeletal (P=0.048), cardiorespiratory (P=0.047), renal (P=0.025), and vascular (P=0.048) complications. Analysis indicated a significant increase in CH50 level in the NAC group after treatment compared to the baseline level (P=0.049). No adverse event was reported by the study subjects.ConclusionsIt appears that the administration of 1800 mg/day NAC to SLE patients can decrease the SLE disease activity and its complications.

Low-dose belimumab for patients with systemic lupus erythematosus at low disease activity: protocol for a multicentre, randomised, double-blind, placebo-controlled clinical trial

IntroductionSLE is a chronic inflammatory systemic autoimmune disease with relapsing–remitting pattern. B-lymphocyte stimulator was involved in the pathogenesis of SLE. The humanised monoclonal antibody belimumab with 10 mg/kg was effective...

BNT162b2 vaccine-induced humoral and cellular responses against SARS-CoV-2 variants in systemic lupus erythematosus

ObjectivesOur aim was to evaluate systemic lupus erythematosus (SLE) disease activity and SARS-CoV-2-specific immune responses after BNT162b2 vaccination.MethodsIn this prospective study, disease activity and clinical assessments were recorded from the...

Why do some patients with systemic lupus erythematosus fail to respond to B-cell depletion using rituximab?

The Centre for Rheumatology has treated 165 lupus patients with rituximab (RTX) since 2000. Our aim was to identify patients who failed to respond, identify any obvious distinguishing features, and to optimise individual patient treatment. We reviewed all 165 lupus patients treated with RTX and reviewed the data up to 6 months after treatment. We excluded those who developed allergic reactions, had discoid lupus only or were lost to follow-up. We assessed patients with active disease after 6 months, using the British Isles Lupus Assessment Group (BILAG) disease activity scores. Those patients whose A and B scores did not decrease, were deemed to have failed to respond. 144 patients were included in the final analysis. The median disease duration was 6.68 (IQR 2.32-11.90) years. 13.9% of the patients failed to decrease their BILAG scores. Two of the 144 patients died during the 6 months after treatment. The median BILAG at baseline was lower in the failure group (8.50, SD 6.00-12.75) at the time of treatment as opposed to those patients who improved (17, SD12.0-23.0) (p<0.001).We found that patients with renal involvement failed less often than those without it (p=0.021). No other significant differences were observed. Patients with a lower BILAG score are less likely to benefit from RTX treatment. Patients with renal involvement were less likely to fail to respond to RTX. We could not identify other features predictive of failure.

Repository corticotropin injection in patients with persistently active SLE requiring corticosteroids: post hoc analysis of results from a two-part, 52-week pilot study.

ObjectivePost hoc analyses evaluated the effectiveness and safety of repository corticotropin injection (RCI) in patients with persistently active SLE over 52 weeks.MethodsPatients were initially randomised to 40 U daily or 80 U every other day RCI (n=26) or placebo (n=12) for the 8-week double-blind period. Completers entered the open-label extension (OLE; n=33) receiving 16, 40 or 80 U RCI 1–3 times/week and were followed through week 52. Outcomes included proportion of responders based on a novel index (resolution of joint or skin activity using hybrid Systemic Lupus Erythematosus Disease Activity Index (hSLEDAI) without any worsening British Isles Lupus Assessment Group (BILAG) scores in other organ systems) or revised novel index (using SLE Responder Index (SRI) definition of BILAG worsening (1A or 2B)), proportion of responders by SRI and changes in total hSLEDAI and BILAG scores. Adverse events and laboratory values were assessed.ResultsAt week 52, 12.0% (3/25) RCI/RCI patients and 36.4% (4/11) placebo/RCI patients were responders using the novel index. The revised novel responder index demonstrated response rates of 48.0% (12/25) and 54.5% (6/11) in the RCI/RCI and placebo/RCI groups, respectively. Proportions of SRI responders were 40.0% (10/25) and 54.5% (6/11). In the RCI/RCI group, total hSLEDAI and BILAG scores declined from 10.0 and 15.7 at week 0 to 3.5 and 4.6 at week 52, respectively. Reductions in the placebo/RCI group on switching were observed (mean hSLEDAI: 9.1–3.3; BILAG: 13.5–2.6). Other disease activity endpoints also improved in both groups. No new safety signals were observed during the OLE.ConclusionsRCI demonstrated durable effectiveness in patients with persistently active SLE despite moderate-dose corticosteroid therapy. Switching from placebo resulted in reduced disease activity during the OLE. These data provide the foundation for evaluation of RCI in a robustly powered study.

Identification of biomarkers of response to abatacept in patients with SLE using deconvolution of whole blood transcriptomic data from a phase IIb clinical trial

ObjectiveTo characterise patients with active SLE based on pretreatment gene expression-defined peripheral immune cell patterns and identify clusters enriched for potential responders to abatacept treatment.MethodsThis post hoc analysis used baseline...

Use of Rituximab in Systemic Lupus Erythematosus: A Single Center Experience Over 14 Years.

To describe the clinical outcome and safety of rituximab (RTX) treatment in systemic lupus erythematosus (SLE) patients with severe manifestations or whose disease is refractory to standard immunosuppressive therapy, treated at a single center. This was a retrospective analysis of all patients with SLE treated with RTX at 1 center between June 2000 and December 2013. The clinical outcome was assessed by determining British Isles Lupus Assessment Group (BILAG) scores and anti-double-stranded DNA (anti-dsDNA) and C3 levels before and 6 months after RTX treatment. For safety analysis, adverse events and deaths were recorded. Of a total of 115 patients, 93.9% were female, the mean ± SD age at diagnosis was 26.39 ± 11.90 years, and the mean ± SD disease duration at first RTX treatment was 91.96 ± 84.80 months. A BILAG score variation of -11.26 ± 11.38 (P < 0.001) was recorded 6 months after the first RTX treatment; 40% of patients had a complete response and 27% had a partial response; in 36.5% of patients, C3 levels increased more than 25%, and in 33.5% anti-dsDNA levels decreased more than 50%. Depletion of CD19+ cells was achieved in 94.0% of patients. Hypogammaglobulinemia was detected in 14.9% of patients, with significant reduction for IgM (P < 0.001) and IgG (P = 0.001) levels. Severe infections, infusion-related reactions, and hypersensitivity reactions occurred in 7%, 3.5%, and 2.6% of patients, respectively. Of the 115 patients, 62 patients had repeated RTX treatments, with an average number of 1.95 ± 1.17 cycles per patient and a mean ± SD interval between infusions of 21.44 ± 20.11 months. At the end of followup, 11 patients were deceased; 6 had cardiovascular events. RTX treatment was effective in decreasing disease activity, with a low incidence of adverse effects.

Efficacy and tolerability of repository corticotropin injection in patients with persistently active SLE: results of a phase 4, randomised, controlled pilot study

ObjectiveTo evaluate the efficacy of a prolonged-release formulation of a porcine adrenocorticotropic hormone analogue (repository corticotropin injection (RCI)) added to standard of care in patients requiring moderate-dose corticosteroids for symptomatic...

Retraction Note to: Correlation of ESR, C3, C4, anti-DNA and lupus activity based on British Isles Lupus Assessment Group Index in patients of rheumatology clinic. Rheumatol Int (2010)30:1605-9.

This study aimed to determine the correlation between of ESR, C3, C4, anti-DNA, and lupus activity and also the construct and criterion validity of the British Isles Lupus Assessment Group (BILAG) index for assessing disease activity in systemic lupus erythematosus (SLE). Patients with SLE were recruited into a cross-sectional study. Data were analyzed for estimating of SLE disease activity [scores on the BILAG index and Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K)]. Overall BILAG scores were determined by the highest score achieved in any of the individual systems in the respective index. Erythrocyte sedimentation rates (ESRs), C3 levels, C4 levels, anti-double-stranded DNA (anti-dsDNA) levels, and SLEDAI-2K scores were used in the analysis of construct validity. Statistical analyses were performed using ordinal logistic regression for construct validity. Of the 100 patients with SLE, 90% were women. Their mean ± SD age was 31.1 ± 9.8 years. Increasing overall scores on the BILAG index were associated with increasing ESRs, decreasing C3 levels, decreasing C4 levels, elevated anti-dsDNA levels, and increasing SLEDAI-2K scores (all P < 0.01). These findings show that the ESR, C3, C4, and anti-DNA should be used in the evaluation and management of patients with SLE. Also the results show that the BILAG index has construct validity.

Urinary podocalyxin and nephrin levels as biomarkers in lupus nephritis patients: Relation to renal involvement and disease activity

Aim of the workTo evaluate the impact of systemic lupus erythematosus (SLE) on urinary levels of podocalyxin and nephrin and to determine their relationship to renal biopsy and disease activity in lupus nephritis (LN) patients. Patients and methodsThe study included 50 LN patients with their renal biopsy classified according to the international society of nephrology. Disease activity was determined using the British Isles Lupus Assessment Group (BILAG). All patients underwent clinical and laboratory evaluation. Urine samples were collected for the assessment of urinary podocalyxin (UPx) and nephrin (UN) by ELISA and for the estimation of protein (UP) and creatinine (Cr) concentrations. The UPx:Cr, UN:Cr and UP:Cr ratios were calculated. ResultsUrinary levels of podocalyxin (593.8±282.2ng/ml), nephrin (304.1±236.8ng/ml) and protein (2.36±0.56g/l) were significantly higher, while urinary creatinine levels (101.4±28.7mg/l) lower in LN patients compared to control (38.1±9ng/ml, 19.2±4.1ng/ml, 0.34±0.13g/l and 155.4±26.7mg/l; p=0.0008, p=0.0003, p=0.00002 and 0.0009, respectively). Consequently, UNCr, UPxCr and UPCr ratios were significantly higher in patients compared to control. There was a significant correlation of the estimated ratios with the LN class and with the BILAG scores being most significant with UPx:Cr ratio. ROC curve and regression analyses defined UPx:Cr ratio as the specific significant predictor of pathological LN grade. ConclusionSLE deleteriously affects fine glomerular structure as reflected by increased urinary levels of podocyte-related proteins; podocalyxin and nephrin. Urinary podocalyxin/creatinine ratio significantly predicts the pathological impact of SLE on the kidney and could be used as a non-invasive marker for such effect and its progression.

THU0509 Longer Duration of B Cell Depletion in Patients with Systemic Lupus Erythematosus is Associated with A Better Outcome

BackgroundWe were alerted to the possibility of very long term B cell depletion (BCD) in Systemic Lupus Erythematosu (SLE) by a patient treated with rituximab in 2001 whose CD19 counts...

SAT0006 The Real (Rapid Evaluation of Activity in Lupus) Correlates Well with Bilag and Sledai

BackgroundDisease activity measures used in clinical studies of lupus, the SLEDAI (SLE Disease Activity Index) and BILAG (British Isles Lupus Assessment Group) are complicated and challenging due to potential scoring...

A156: Pharmacokinetics and Pharmacogenetics of Mycophenolic Acid and Response to Therapy in Childhood‐Onset Systemic Lupus Erythematosus

Background/Purpose:Mycophenolate mofetil (MMF) is a prodrug that is pre‐systemically hydrolyzed by esterases to the biologically active mycophenolic acid (MPA) and is mainly inactivated by UDP‐glucuronosyltransferases (UGTs) in the liver, intestine and kidney. MMF has been used off‐label in SLE because of its favorable side effect spectrum. Optimal MMF dosing in childhood‐onset SLE (cSLE) is not well‐established. Little is known about the pharmacokinetics (PK) and pharmacogenetics (PG) of MPA in cSLE although in pediatric transplant populations, graft survival is more closely related to individualized dosing based on systemic exposure (PK) to MPA rather than weight‐adjusted dosing. Transplant literature has also elucidated the potential influence of genetic variants in UGTs on the large variability of MPA exposure and the occurrence of common MMF‐associated adverse events. The purpose of this study is to explore the importance and potential benefits of individualized MMF therapy in cSLE by determining whether MPA PK correlates with cSLE therapeutic response and whether MPA PG influences MMF exposure.Methods:Full 9‐hour pharmacokinetic profiles were obtained from cSLE patients (n = 18; F:M = 17:1; age 10–30 years, 43% Caucasian, 57% African‐American, 81% non‐Hispanic) who were on stable MMF therapy. The MPA PK parameters dose‐normalized area under the curve from 0 to 12 hours (AUC0–12h), peak concentration (Cmax), time to peak concentration (Tmax) and oral clearance (CL/F) were assessed and analyzed by non‐compartmental analysis. Genomic DNA was extracted using standard procedures and genotyped for UGT1A8*3 (830G&gt;A), UGT1A9*3 (98T&gt;C), 1A9–2152T&gt;C, 1A9–440C&gt;T, 1A9–331T&gt;C, 1A9–275T&gt;A and UGT2B7–900A&gt;G by TaqMan assay and direct sequencing. Change in SLE disease activity while on MMF was measured using the British Isles Lupus Assessment Group (BILAG) index.Results:Large inter‐patient variability in AUC0–12h (mean + S.D.: 38.7 + 19.8 mg hr/L/gMPA, range: 14.9–95.4) and oral clearance (CL/F) of MPA (mean + S.D.: 27.9 + 13.7 L/hr, range: 8.3–59.3) was observed. The AUC0–12h and weight‐adjusted MMF dosing were only moderately correlated (r = 0.56, P = 0.01). An AUC0–12h of &gt;30 mg hr/L was associated with decreased BILAG scores while on MMF (P = 0.002). Patients with UGT1A9 –440T (–331C) or UGT2B7 –900G appeared to have a trend toward lower CL/F and higher MPA exposure (AUC) than the wild‐type of all evaluated single nucleotide polymorphisms. Patients with UGT1A9 –275A showed relatively high CL/F over a wide range. In an exploratory fashion, wild‐type and –275A‐carriers were analyzed and showed significantly higher CL/F compared to the rest of the carriers of SNPs 1A9 –440T (–331C) or 2B7 –900G (p &lt; 0.05, Mann‐Whitney's U test).Conclusion:Our data suggest that weight‐adjusted MMF dosing alone does not reliably allow for the prediction of exposure to MPA in cSLE and that MPA exposure measured as AUC0–12h of at least 30 mg hr/L is required for cSLE improvement. UGT1A9 and UGT2B7 polymorphisms accounted in part for inter‐individual differences in MPA exposure in patients with cSLE.

Umbilical cord mesenchymal stem cell transplantation in active and refractory systemic lupus erythematosus: a multicenter clinical study

IntroductionIn our present single-center pilot study, umbilical cord (UC)–derived mesenchymal stem cells (MSCs) had a good safety profile and therapeutic effect in severe and refractory systemic lupus erythematosus (SLE). The present multicenter clinical trial was undertaken to assess the safety and efficacy of allogeneic UC MSC transplantation (MSCT) in patients with active and refractory SLE.MethodsForty patients with active SLE were recruited from four clinical centers in China. Allogeneic UC MSCs were infused intravenously on days 0 and 7. The primary endpoints were safety profiles. The secondary endpoints included major clinical response (MCR), partial clinical response (PCR) and relapse. Clinical indices, including Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, British Isles Lupus Assessment Group (BILAG) score and renal functional indices, were also taken into account.ResultsThe overall survival rate was 92.5% (37 of 40 patients). UC-MSCT was well tolerated, and no transplantation-related adverse events were observed. Thirteen and eleven patients achieved MCR (13 of 40, 32.5%) and PCR (11 of 40, 27.5%), respectively, during 12 months of follow up. Three and four patients experienced disease relapse at 9 months (12.5%) and 12 months (16.7%) of follow-up, respectively, after a prior clinical response. SLEDAI scores significantly decreased at 3, 6, 9 and 12 months follow-up. Total BILAG scores markedly decreased at 3 months and continued to decrease at subsequent follow-up visits. BILAG scores for renal, hematopoietic and cutaneous systems significantly improved. Among those patients with lupus nephritis, 24-hour proteinuria declined after transplantation, with statistically differences at 9 and 12 months. Serum creatinine and urea nitrogen decreased to the lowest level at 6 months, but these values slightly increased at 9 and 12 months in seven relapse cases. In addition, serum levels of albumin and complement 3 increased after MSCT, peaked at 6 months and then slightly declined by the 9- and 12-month follow-up examinations. Serum antinuclear antibody and anti-double-stranded DNA antibody decreased after MSCT, with statistically significant differences at 3-month follow-up examinations.ConclusionUC-MSCT results in satisfactory clinical response in SLE patients. However, in our present study, several patients experienced disease relapse after 6 months, indicating the necessity to repeat MSCT after 6 months.Trial registryClinicalTrials.gov identifier: NCT01741857. Registered 26 September 2012.

AB0220 Serum phosphatidylserine-specific phospholipase A1 (PS-PLA1) is increased in active systemic lupus erythematosus (SLE) and is correlated with disease activity

BackgroundLysophospholipids (LPLs) such as lysophosphatidic acid (LPA) and lysophosphatidylserine (LPS) are lipid mediators with multiple biological roles including immuno-regulatory functions (1,2). LPA and LPS are known to be produced by...

Rituximab in the treatment of resistant lupus nephritis: therapy failure in rapidly progressive crescentic lupus nephritis

The objective of this paper is to report the clinical outcome of B cell depletion therapy in 18 patients with refractory lupus nephritis (LN). Eighteen patients received rituximab on an open-label basis with prospective evaluations. All patients had renal disease refractory to conventional immunosuppressive therapy, including intravenous cyclophosphamide (CyC). All patients fulfilled the revised ACR classification criteria for SLE. Rituximab was given as 2 × 1 g infusions with 500 mg iv CyC and 500 mg iv methylprednisolone, two weeks apart. Complete remission (CR) of nephritis at six months was defined as normal serum creatinine and serum albumin levels, inactive urine sediment, and proteinuria < 0.5 g/day; partial remission (PR) was defined as a ≥50% improvement in all renal parameters that were abnormal at baseline. Clinical response was assessed by the British Isles Lupus Assessment Group (BILAG) score pre- and post-rituximab treatment, and efficacy was recorded by extent and duration of B lymphocyte depletion (normal range 0.100-0.500 × 10(9)/l). Follow-up data were collected at six months, one year post-treatment and at the most recent clinic visit. At six months, 11/18 patients reached renal CR and two of 18 PR. The mean global BILAG scores for responders decreased from 15 (SD 10) to 5 (SD 3), and a total of ten A scores disappeared. Five patients failed to show complete or partial renal response despite peripheral B lymphocyte count depletion, and progressed to end-stage renal failure (ESRF) and dialysis. Four of these patients had severe proliferative, crescentic nephritis, of whom three had Class IV-G, one Class III and one late membranous glomerulonephritis. One patient died six years after rituximab therapy from overwhelming sepsis while on long-term haemodialysis. Rituximab therapy achieved a response in 13/18 patients with refractory LN. However, in patients with rapidly progressive crescentic LN, when there is already evidence of significant renal impairment, rituximab therapy may not prevent progression to ESRF and dialysis. Our data also suggest that severe Class IV-G LN may be associated with a poor response to therapy.

Brief Report: Attention Deficit and Hyperactivity Disorder Scores Are Elevated and Respond to N‐Acetylcysteine Treatment in Patients With Systemic Lupus Erythematosus

To investigate whether attention deficit hyperactivity disorder (ADHD) may serve as a marker of neuropsychiatric disease and as a target for N-acetylcysteine (NAC) treatment in patients with systemic lupus erythematosus (SLE). The ADHD Self-Report Scale (ASRS) was used to assess 49 patients with SLE and 46 matched healthy control subjects. Twenty-four of the patients with SLE were randomized to receive either placebo, NAC at a dosage of 2.4 gm/day, or NAC at a dosage of 4.8 gm/day. Disease activity was evaluated monthly using the British Isles Lupus Assessment Group (BILAG) index, the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), the Fatigue Assessment Scale (FAS), and the ASRS, before and during the 3-month treatment period and after a 1-month washout period. The cognitive/inattentive (ASRS part A), hyperactivity/impulsive (ASRS part B), and combined (total) ASRS scores were increased in patients with SLE compared with control subjects (mean ± SEM 17.37 ± 1.03 [P = 3 × 10(-7) ], 14.51 ± 0.89 [P = 2 × 10(-4) ], and 31.92 ± 1.74 [P = 8 × 10(-7) ], respectively, versus 10.41 ± 1.02, 9.61 ± 1.21, and 20.02 ± 1.98, respectively. ASRS part A scores correlated with SLEDAI (r = 0.53, P < 0.0001) and BILAG scores (r = 0.36, P = 0.011). ASRS total scores also correlated with SLEDAI (r = 0.45, P = 0.0009) and BILAG scores (r = 0.31, P = 0.025). ASRS part A (r = 0.73, P < 0.0001), ASRS part B (r = 0.47, P = 0.0006), and ASRS total scores (r = 0.67, P < 0.0001) correlated with the FAS score. Relative to the scores in placebo-treated patients, ASRS total scores were reduced in SLE patients treated with NAC dosages of 2.4 gm/day and 4.8 gm/day combined (P = 0.037). ASRS part A scores were reduced by NAC dosages of 2.4 gm/day (P = 0.001) and 4.8 gm/day (P < 0.0001) as well as by NAC at dosages of 2.4 gm/day and 4.8 gm/day combined (P = 0.001). In patients with SLE, elevated ASRS scores reveal previously unrecognized and clinically significant symptoms of ADHD that respond to NAC treatment.

N‐acetylcysteine reduces disease activity by blocking mammalian target of rapamycin in T cells from systemic lupus erythematosus patients: A randomized, double‐blind, placebo‐controlled trial

Systemic lupus erythematosus (SLE) patients exhibit T cell dysfunction, which can be regulated through mitochondrial transmembrane potential (Δψm) and mammalian target of rapamycin (mTOR) by glutathione (GSH). This randomized, double-blind, placebo-controlled study was undertaken to examine the safety, tolerance, and efficacy of the GSH precursor N-acetylcysteine (NAC). A total of 36 SLE patients received either daily placebo or 1.2 gm, 2.4 gm, or 4.8 gm of NAC. Disease activity was evaluated monthly by the British Isles Lupus Assessment Group (BILAG) index, the SLE Disease Activity Index (SLEDAI), and the Fatigue Assessment Scale (FAS) before, during, and after a 3-month treatment period. Mitochondrial transmembrane potential and mTOR were assessed by flow cytometry. Forty-two healthy subjects matched to patients for age, sex, and ethnicity were studied as controls. NAC up to 2.4 gm/day was tolerated by all patients, while 33% of those receiving 4.8 gm/day had reversible nausea. Placebo or NAC 1.2 gm/day did not influence disease activity. Considered together, 2.4 gm and 4.8 gm NAC reduced the SLEDAI score after 1 month (P = 0.0007), 2 months (P = 0.0009), 3 months (P = 0.0030), and 4 months (P = 0.0046); the BILAG score after 1 month (P = 0.029) and 3 months (P = 0.009); and the FAS score after 2 months (P = 0.0006) and 3 months (P = 0.005). NAC increased Δψm (P = 0.0001) in all T cells, profoundly reduced mTOR activity (P = 0.0009), enhanced apoptosis (P = 0.0004), reversed expansion of CD4-CD8- T cells (mean ± SEM 1.35 ± 0.12-fold change; P = 0.008), stimulated FoxP3 expression in CD4+CD25+ T cells (P = 0.045), and reduced anti-DNA production (P = 0.049). This pilot study suggests that NAC safely improves lupus disease activity by blocking mTOR in T lymphocytes.

Urinary monocyte chemoattractant protein 1 and alpha 1 acid glycoprotein as biomarkers of renal disease activity in juvenile-onset systemic lupus erythematosus

A higher proportion of patients with juvenile-onset systemic lupus erythematosus (JSLE) will have renal involvement compared with adult-onset disease, some progressing to renal failure in adulthood. Histological examination is the gold standard for diagnosing lupus nephritis (LN), but its invasive nature limits routine use. Using cross-sectional cohort analysis, we aimed to determine whether urinary concentrations of monocyte chemoattractant protein-1 (MCP1), alpha-1-acid glycoprotein (AGP) and interferon-inducible protein 10 (IP10) are biomarkers of active LN. Sixty JSLE patients recruited to the UK JSLE Cohort Study were categorized according to the British Isles Lupus Assessment Group (BILAG) activity index. Patients with active renal JSLE (n = 8; renal BILAG score A, B) had significantly higher urinary MCP1 concentrations than patients with inactive renal disease (n = 52; renal BILAG score C, D, E; 582 pg/mg creatinine [Cr], 207 pg/mg Cr; p = 0.018) or healthy controls (n = 23; 117 pg/mg Cr; p = 0.005). Urinary AGP concentration was significantly elevated in patients with active renal disease compared with inactive renal disease (1517 ng/mg Cr, 485 ng/mg Cr; p = 0.027) or healthy controls (313 ng/mg Cr; p = 0.013). Urinary IP10 concentration was not significantly different between groups, but did strongly correlate with uMCP and uAGP levels (rho = 0.38, p = 0.009; rho = 0.33, p = 0.021). Urinary MCP1 and AGP are biomarkers of LN, providing insight into its pathophysiology. Longitudinal studies are warranted.

B cell biomarkers of rituximab responses in systemic lupus erythematosus

Rituximab appears to be effective in many studies of systemic lupus erythematosus (SLE), with variable initial clinical response and time to relapse. However, results of a randomized controlled trial of rituximab were negative. This study was undertaken to evaluate the effectiveness of rituximab in SLE, using highly sensitive flow cytometry (HSFC), which can define B cell numbers 50-100 times lower than conventional techniques and predicts responses in rheumatoid arthritis. Thirty-nine patients with active SLE were started on a standard regimen of rituximab with intravenous and oral steroids. Clinical response and relapse were defined using the British Isles Lupus Assessment Group (BILAG) index with criteria for major clinical response, partial clinical response, and nonresponse. HSFC, including analysis of B cell subsets, was performed. There was a significant reduction from baseline in global BILAG score at all time points analyzed (P<0.0001), and major clinical response and partial clinical response rates were 51% and 31%, respectively. Time to relapse was highly variable. Fifty percent of the patients relapsed after 6-18 months (earlier relapse); the remainder relapsed at a slower rate (later relapse). B cell depletion and repopulation were variable and were predictive of these clinical outcomes. There was a persistent B cell presence in 21 patients after 2 infusions of rituximab, which included all 7 patients with no response (P=0.012 versus patients with complete depletion of B cells). Memory B cell (P=0.02) and plasmablast (P<0.001) repopulation after 26 weeks was markedly faster in patients with earlier relapse versus patients with later relapse. Our findings indicate that rituximab is effective in SLE, and clinical responses are supported by close correlation with B cell numbers. HSFC is a valuable tool in the assessment and prediction of response in SLE.