British Isles Lupus Assessment Group Index Research Articles

Serum Levels of T Cell Immunoglobulin and Mucin-Domain Containing Molecule 3 in Patients with Systemic Lupus Erythematosus.

Objective: T cell immunoglobulin and mucin-domain-containing molecule 3 (TIM-3) is implicated in the development of various autoimmune diseases. We aimed to investigate the levels of soluble TIM-3 (sTIM-3) and their associations between clinical parameters in patients with systemic lupus erythematosus (SLE). Methods: Serum samples were collected from 65 patients with SLE and 35 age-matched healthy controls (HCs). The SLE Disease Activity Index 2000 (SLEDAI-2K) and the Systemic Lupus International Collaborating Clinics (SLICC) damage index (SDI) were used to assess SLE disease activity and SLE-related organ damage. British Isles Lupus Assessment Group (BILAG)-2004 index was also used to assess SLE disease activity. Soluble TIM-3 (sTIM-3) in sera from patients with SLE and HCs were evaluated by enzyme-linked immunosorbent assay (ELISA). The results were compared with the clinical parameters of SLE including SLE disease activity. Results: Serum sTIM-3 levels in patients with SLE (median 2123 pg/mL (interquartile range (IQR), 229–7235)) were significantly higher than those in HCs (1363 pg/mL; IQR, 1097–1673; p = 0.0015). Serum levels of sTIM-3 were correlated with disease activity of SLE using the SLEDAI-2K score (p < 0.001, r = 0.53). The serum sTIM-3 levels in SLE patients with active renal disease (BILAG renal index A-B) were significantly higher than those without the active renal disease (BILAG renal index C–E). However, no significant difference was observed in serum sTIM-3 levels between SLE patients with and without active involvement in other organs (BILAG index). Serum sTIM-3 levels were significantly elevated in SLE patients with organ damage (2710 pg/mL; IQR, 256–7235) compared to those without organ damage (1532 pg/mL; IQR, 228–5274), as assessed by the SDI (p = 0.0102). Conclusions: Circulating sTIM-3 levels are elevated in SLE patients, and serum sTIM-3 levels are associated with SLE disease activity and SLE-related organ damage. The data indicate a possible link between the TIM-3/Gal-9 pathway and SLE clinical phenotypes, and further investigation of the TIM-3 pathway in SLE pathophysiology is warranted.

Interferon blockade in systemic lupus erythematosus: Light at the end of the tunnel for novel therapies for lupus?

Interferon blockade in systemic lupus erythematosus: Light at the end of the tunnel for novel therapies for lupus?

Trial of Anifrolumab in Active Systemic Lupus Erythematosus

BackgroundAnifrolumab, a human monoclonal antibody to type I interferon receptor subunit 1 investigated for the treatment of systemic lupus erythematosus (SLE), did not have a significant effect on the primary end point in a previous phase 3 trial. The current phase 3 trial used a secondary end point from that trial as the primary end point.MethodsWe randomly assigned patients in a 1:1 ratio to receive intravenous anifrolumab (300 mg) or placebo every 4 weeks for 48 weeks. The primary end point of this trial was a response at week 52 defined with the use of the British Isles Lupus Assessment Group (BILAG)–based Composite Lupus Assessment (BICLA). A BICLA response requires reduction in any moderate-to-severe baseline disease activity and no worsening in any of nine organ systems in the BILAG index, no worsening on the Systemic Lupus Erythematosus Disease Activity Index, no increase of 0.3 points or more in the score on the Physician Global Assessment of disease activity (on a scale from 0 [no disease activity] to 3 [severe disease]), no discontinuation of the trial intervention, and no use of medications restricted by the protocol. Secondary end points included a BICLA response in patients with a high interferon gene signature at baseline; reductions in the glucocorticoid dose, in the severity of skin disease, and in counts of swollen and tender joints; and the annualized flare rate.ResultsA total of 362 patients received the randomized intervention: 180 received anifrolumab and 182 received placebo. The percentage of patients who had a BICLA response was 47.8% in the anifrolumab group and 31.5% in the placebo group (difference, 16.3 percentage points; 95% confidence interval, 6.3 to 26.3; P=0.001). Among patients with a high interferon gene signature, the percentage with a response was 48.0% in the anifrolumab group and 30.7% in the placebo group; among patients with a low interferon gene signature, the percentage was 46.7% and 35.5%, respectively. Secondary end points with respect to the glucocorticoid dose and the severity of skin disease, but not counts of swollen and tender joints and the annualized flare rate, also showed a significant benefit with anifrolumab. Herpes zoster and bronchitis occurred in 7.2% and 12.2% of the patients, respectively, who received anifrolumab. There was one death from pneumonia in the anifrolumab group.ConclusionsMonthly administration of anifrolumab resulted in a higher percentage of patients with a response (as defined by a composite end point) at week 52 than did placebo, in contrast to the findings of a similar phase 3 trial involving patients with SLE that had a different primary end point. The frequency of herpes zoster was higher with anifrolumab than with placebo. (Funded by AstraZeneca; ClinicalTrials.gov number, NCT02446899.)

Withdrawal of low-dose prednisone in SLE patients with a clinically quiescent disease for more than 1 year: a randomised clinical trial

ObjectivesTo compare the efficacy to prevent flares of maintenance versus withdrawal of 5 mg/day prednisone in systemic lupus erythematosus (SLE) patients with clinically quiescent disease.MethodsA monocentric, 12-month, superiority, open-label, randomised...

Sirolimus in patients with clinically active systemic lupus erythematosus resistant to, or intolerant of, conventional medications: a single-arm, open-label, phase 1/2 trial

Patients with systemic lupus erythematosus have T-cell dysfunction that has been attributed to the activation of the mammalian target of rapamycin (mTOR). Rapamycin inhibits antigen-induced T-cell proliferation and has been developed as a medication under the generic designation of sirolimus. We assessed safety, tolerance, and efficacy of sirolimus in a prospective, biomarker-driven, open-label clinical trial. We did a single-arm, open-label, phase 1/2 trial of sirolimus in patients with active systemic lupus erythematosus disease unresponsive to, or intolerant of, conventional medications at the State University of New York Upstate Medical University (Syracuse, NY, USA). Eligible participants (aged ≥18 years) had active systemic lupus erythematosus fulfilling four or more of 11 diagnostic criteria defined by the American College of Rheumatology. We excluded patients with allergy or intolerance to sirolimus, patients with life-threatening manifestations of systemic lupus erythematosus, proteinuria, a urine protein to creatinine ratio higher than 0·5, anaemia, leucopenia, or thrombocytopenia. Patients received oral sirolimus at a starting dose of 2 mg per day, with dose adjusted according to tolerance and to maintain a therapeutic range of 6-15 ng/mL. Patients were treated with sirolimus for 12 months. Safety outcomes included tolerance as assessed by the occurrence of common side-effects. The primary efficacy endpoint was decrease in disease activity, assessed using the British Isles Lupus Assessment Group (BILAG) index and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Blood samples of 56 matched healthy individuals were obtained as controls for immunobiological outcomes monitored at each visit. The primary efficacy endpoint was assessed in all patients who completed 12 months of treatment, and all patients who received at least one dose of treatment were included in the safety analyses. This trial is registered with ClinicalTrials.gov, number NCT00779194. Between March 9, 2009, and Dec 8, 2014, 43 patients were enrolled, three of whom did not meet eligibility criteria. 11 of the 40 eligible patients discontinued study treatment because of intolerance (n=2) or non-compliance (n=9). SLEDAI and BILAG disease activity scores were reduced during 12 months of treatment in 16 (55%) of 29 patients who completed treatment. Mean SLEDAI score decreased from 10·2 (SD 5·6) at enrolment to 4·8 (4·5) after 12 months of treatment (p<0·001) and the mean total BILAG index score decreased from 28·4 (12·4) at enrolment to 17·4 (10·7) after 12 months of treatment (p<0·001). The mean daily dose of prednisone required to control disease activity decreased from 23·7 mg (SD 9·6) to 7·2 mg (2·3; p<0·001) after 12 months of treatment. Sirolimus expanded CD4+CD25+FoxP3+ regulatory T cells and CD8+ memory T-cell populations and inhibited interleukin-4 and interleukin-17 production by CD4+ and CD4-CD8- double-negative T cells after 12 months. CD8+ memory T cells were selectively expanded in SRI-responders. Patient liver function and lymphocyte counts were unchanged. Although HDL-cholesterol (Z=-2·50, p=0·012), neutrophil counts (Z=-1·92, p=0·054), and haemoglobin (Z=-2·83, p=0·005) were moderately reduced during treatment, all changes occurred within a range that was considered safe. Platelet counts were slightly elevated during treatment (Z=2·06, p=0·0400). These data show that a progressive improvement in disease activity is associated with correction of pro-inflammatory T-cell lineage specification in patients with active systemic lupus erythematosus during 12 months of sirolimus treatment. Follow-up placebo-controlled clinical trials in diverse patient populations are warranted to further define the role of mTOR blockade in treatment of systemic lupus erythematosus. Pfizer, the National Institutes of Health, and the Central New York Community Foundation.

The Association Between Erythrocyte Sedimentation Rate, C3, C4, Anti-dsDNA Levels, and Renal Disease Activity, Based on BILAG Index in Females With Lupus Nephritis

Background: Systemic lupus erythematosus (SLE) is a chronic inflammatory disease that involves many organs, such as the kidneys. Females are most affected and early detection of renal disease activity is very important for morbidity and mortality reduction. Objectives: The aim of this study was to determine the relationships between ESR, C3, C4, and anti-dsDNA levels and renal disease activity, based on renal components of the British Isles lupus assessment group (BILAG) index, in females with lupus nephritis (LN). Methods: This study retrospectively reviewed the medical files of 150 females, diagnosed as LN, who were on routine follow-up at Hafez hospital lupus clinic located in Shiraz, Southern part of Iran (during years 2014 to 2015). The BILAG index score was extracted and data was analyzed (α = 0.05). Results: In all 150 females with SLE, the mean (SD) age was 37.1 (10.6) years. There were significant relationships between BILAG index score and higher ESR level (P value = 0.01), positive anti-dsDNA (P value < 0.001) and low C4 level (P value = 0.003), statistically. However, the results were not significant for mild level of ESR and low level of C3. Conclusions: This study confirmed that the BILAG index score was a valuable predictive index for renal disease involvement in females with LN; thus the authors suggest clinicians to use this index for better LN management.

Mycobacterium tuberculosis infection in systemic lupus erythematosus patients

Aim of the workTo estimate prevalence of tuberculosis (TB) infection in systemic lupus erythematosus (SLE) patients; to study its relation to disease duration, activity, damage and treatment as well as to compare the performance of interferon gamma (IFN-γ) release assay and tuberculin skin test (TST) in detection of TB infection. Patients and methodsThe study enrolled 100 adult SLE patients. Disease activity was assessed using the British Isles Lupus Assessment Group (BILAG) activity index and damage using the Systemic Lupus International Collaborative Clinics damage Index (SLICCDI). Tuberculin skin tests and QuantiFERON-TB GOLD In-Tube (QFT-GIT) test were performed. ResultsThe mean age of the patients was 29.82±7.9years; 90% females and 10% males with a mean disease duration 5.5±5.4years. The BILAG index showing that 30% had category A renal activity and the mean of SLICCDI was 1.4±1.7. All patients were Bacille Calmette-Guérin(BCG) vaccinated; none of them had a previous history or contact to members with TB infection. QFT-GIT was positive in 13 patients and TST was positive in 2 patients. 15 patients were diagnosed as latent tuberculosis infection (LTBI). No patients were identified with active TB and microscopic examination and culture were negative. The agreement between the QFT-GIT and TST was poor. No significant difference between patients with positive and negative QFT-GIT results as regard disease duration, corticosteroids and immunosuppressive drugs used, BILAG, SLICCDI, chest X-ray and laboratory investigations. ConclusionThe prevalence of LTBI in SLE patients in our study was 15% with poor agreement between the QFT-GIT and TST.

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.

Vitamin D deficiency and its association with disease activity in new cases of systemic lupus erythematosus

Evidence has shown a relationship between vitamin D deficiency and systemic lupus erythematosus (SLE). We evaluated the frequency of vitamin D deficiency and its association with disease activity in new cases of SLE. Women with newly diagnosed SLE, based on the American College of Rheumatology (ACR) criteria, were enrolled consecutively. Those receiving vitamin D supplements and postmenopausal women were not included. Disease activity was measured by the BILAG index (2004) and serum concentration of 25-hydroxyvitamin D (25[OH]D) was measured by radioimmunoassay method. Forty SLE patients with mean age of 25.3 ± 4.2 years were studied. Severe, moderate, and mild vitamin D deficiency, corresponding to serum 25[OH]D concentrations of <12.5, 12.5-24.9, and 25-39.9 nmol/l, were found in 12.5%, 62.5%, and 17.5% of the patients, respectively. Serum 25[OH]D concentration was inversely correlated with the British Isles Lupus Assessment Group (BILAG) index score (r = -0.486, p = 0.001). Those with a more severe vitamin D deficiency had also higher concentrations of liver enzymes (p < 0.05), lower serum albumin and hemoglobin concentrations (p < 0.05), and higher titers of antibodies to double-stranded DNA (ds-DNA) (p < 0.001). This study showed that most of the SLE patients in our society have vitamin D deficiency at the time of diagnosis that is associated with a higher disease activity. Routine screening for vitamin D deficiency and its prompt treatment in patients with newly diagnosed SLE is recommended.

Urinary monocyte chemoattractant protein-1 correlates with disease activity in lupus nephritis

Monocyte chemoattractant protein-1 (MCP-1) has a pathogenic role in murine lupus nephritis (LN). We recruited 25 pediatric and adolescent systemic lupus erythematosus (SLE) patients from our lupus clinic [13 (52%) patients with LN and 12 (48%) lupus non-nephritis patients] and evaluated their urinary and plasma MCP-1 levels compared to adult and childhood controls. The median age and SLE disease duration of patients were 14.4 and 5.5 years, respectively. LN patients had a higher median renal (p=0.01) British Isles Lupus Assessment Group (BILAG) index, with a tendency for higher total BILAG scores (p=0.2). There were significantly increased urinary MCP-1 levels in the LN patients compared to healthy controls (p<0.001) whose values were significantly higher than lupus non-nephritis children (p<0.004). Urinary MCP-1 levels correlated well with total BILAG scores (r=0.82, p=0.04). There were no differences in plasma MCP-1 levels between SLE patient groups and pediatric controls, although the levels in the childhood controls were elevated compared to those of the adult controls (p<0.04). These results provide evidence of increased urinary--but not plasma--MCP-1 levels in children with LN, which correlates well with SLE disease activity as measured by the BILAG index.

Raised serum level of APRIL in patients with systemic lupus erythematosus: Correlations with disease activity indices

The aim of the present study is to assess serum APRIL levels in SLE patients versus rheumatoid arthritis (RA) patients and normal control and to correlate serum APRIL levels in SLE patients with disease activity indices. Serum APRIL levels was measured in 40 SLE patients, 20 patients with RA and 20 healthy volunteers who served as control group. Disease activity in SLE patients was assessed by the British Isles Lupus Assessment Group (BILAG) index and SLE disease activity index (SLEDAI), and results were correlated with serum APRIL levels. Significantly higher serum APRIL levels was observed in SLE patients compared to RA patients and normal controls (p=0.003 and p < or = 0.001, respectively). Positive correlations were found between serum APRIL levels and total BILAG index (r=0.486 and p=0.001), BILAG musculoskeletal score (r=0.848 and p < or = 0.001) and BILAG cardiorespiratory score (r=0.326 and 0.04). Serum APRIL was higher in SLE patients compared to RA patients and normal control subjects and positively correlates with BILAG index and higher levels may be associated with musculoskeletal manifestations of the disease. APRIL antagonism could be a potential therapeutic target in SLE.

RETRACTED ARTICLE: Correlation of ESR, C3, C4, anti-DNA and lupus activity based on British Isles Lupus Assessment Group Index in patients of rheumatology clinic

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.

Mycophenolate Mofetil for Remission Induction in Severe Lupus Nephritis

Background: Mycophenolate mofetil (MMF) is a potential alternative immunosuppressive to cyclophosphamide or azathioprine for the treatment of lupus nephritis. It has a superior toxicity profile to cyclophosphamide and is more effective than azathioprine when used in combination with cyclosporin for renal transplantation. Methods: This open label study assessed the safety and efficacy of an induction regimen of MMF and prednisolone in 24 patients, with active WHO Class III, IV or V lupus nephritis, without previous exposure to cyclophosphamide or MMF. Patients received MMF 2 g/day and a tapering dose of oral prednisolone and were followed for 12 months. Renal response was defined using the validated BILAG (British Isles Lupus Assessment Group) Index. Results: 20 patients achieved complete renal remission, 2 partial renal remission and 2 had renal disease refractory to MMF. Five patients were withdrawn, 2 for progressive renal disease, 2 for extra-renal flares and 1 following a severe infection. No patient was withdrawn for drug intolerance. There were 18 adverse events of which 10 were infections. Clinical improvement was mirrored by normalisation of complement levels and marked falls in circulating anti-double-stranded DNA antibodies. Follow-up for a mean period of 35 months documented only one episode of renal relapse which subsequently remitted with re-introduction of MMF. One patient died after 18 months’ follow-up with uterine malignancy. Conclusions: MMF with prednisolone was effective for remission induction in severe lupus nephritis and was well tolerated.

The use of the British Isles Lupus Assessment Group (BILAG) index as a valid tool in assessing disease activity in childhood-onset systemic lupus erythematosus.

The British Isles Lupus Assessment Group (BILAG) index is a standardized systemic lupus erythematosus (SLE) disease activity assessment. The main aim of this study was to correlate the BILAG index with laboratory measures of disease activity in childhood-onset SLE with and without biopsy-proven lupus nephritis. Prospective observational comparison study of the BILAG index in 21 SLE patients under 18 yr of age over a 12-month period in a tertiary referral paediatric outpatient clinic. Eleven patients with lupus non-nephritis and 10 patients with lupus nephritis were reviewed. The lupus nephritis patients had significantly (P<0.001) more admissions over a similar time interval since diagnosis. The renal BILAG disease activity scores were significantly greater (P = 0.013) in the lupus nephritis group (range 1-9, median 3.0, compared with 0-3 and 1.0 in the lupus non-nephritis group). The total BILAG scores and patient visual analogue scores (VAS) were higher in the lupus nephritis groups, unlike the lower physician VAS, but these differences were not statistically significant compared with other laboratory indices of disease activity. The BILAG index is a useful tool in monitoring disease activity in children and adolescents with SLE. The data collected for the BILAG index can be used serially and effectively by different clinicians over time to enable recording of disease status at sequential assessments. The lower patient VAS in the lupus non-nephritis group was not significant and may reflect the patients' own perception of lethargy at times of increased disease activity.

Further validation of the BILAG disease activity index in patients with systemic lupus erythematosus.

To examine the association among the BILAG disease activity index components and their relations with global assessments, health status, and laboratory tests with regard to the validity of the BILAG index. A cross sectional study of consecutive patients with systemic lupus erythematosus (SLE) attending a specialist lupus outpatient clinic between July 1994 and February 1995. The internal consistency of the British Isles Lupus Assessment Group (BILAG) index-a disease activity assessment system for SLE patients, based on the principle of the physician's intention to treat-was examined using Cronbach's coefficient alpha. The association of the components of the BILAG index with health status as measured with the MOS Short Form 20 (SF-20), with patients' and doctors' global assessments of patient wellbeing and with laboratory tests was analysed with Spearman rank correlations. 133 female and eight male patients, age 20.1 to 88.7 years (mean 41.1, SD 12.5), were included. With few exceptions, the components of the BILAG index which reflect disease activity in different organ systems were not associated with each other. With the exception of the mucocutaneous component, we found a significant relation between all components of BILAG and global assessment of patient wellbeing, health status, erythrocyte sedimentation rate, or serum C3 level. The study confirms the validity of all but the mucocutaneous component of the BILAG index. However, disease activity in different organ systems in SLE does not follow a common pattern. Thus the individual BILAG components should be used rather than the total BILAG score as a primary endpoint in clinical and epidemiological studies. To capture the total effect of SLE on an individual measures of disease activity, damage, and health status are all needed.

Antineutrophil cytoplasmic antibodies in systemic lupus erythematosus

To examine the prevalence, subspecificities, and clinical associations of antineutrophil cytoplasmic antibodies (ANCA) in patients with systemic lupus erythematosus (SLE). One hundred fifty-seven sera from 120 patients with SLE were examined for classic (c) and perinuclear (p) pattern ANCA by indirect immunofluorescence. Antibody subspecificities were determined by enzyme-linked immunosorbent assay (ELISA). Serologic results were correlated with clinical manifestations as categorized by the BILAG (British Isles Lupus Assessment Group) index. ANCA were found in 40 of the 157 sera (25%). Only a pANCA, not a cANCA, pattern of fluorescence was seen. By ELISA testing, 16 sera reacted to lactoferrin, 8 to elastase, and 4 to lysozyme. There was no reactivity to proteinase 3 (PR3) or myeloperoxidase (MPO). No correlation of pANCA, or any of the ANCA subspecificities, with organ system involvement, as categorized by the BILAG index, was found. Notably, there was no correlation of ANCA results with lupus vasculitis. The absence of cANCA, anti-PR3, and anti-MPO shows that with appropriate assay conditions, ANCA testing assists in the differentiation between SLE and the ANCA-associated vasculitides. The lack of a correlation between pANCA or any ANCA subspecificity and clinical manifestations suggests that ANCA do not identify particular clinical subsets among SLE patients, including those with lupus vasculitis.

Urine neopterin: a new parameter for serial monitoring of disease activity in patients with systemic lupus erythematosus.

To investigate the role of serial measurement of urine neopterin concentration in monitoring the progression of systemic lupus erythematosus (SLE) disease activity scored using the British Isles Lupus Assessment Group (BILAG) index. We followed prospectively 68 unselected SLE patients for a total of 464 patient months during which 233 separate assessments were carried out. At each assessment, urine neopterin, determined by high performance liquid chromatography, together with erythrocyte sedimentation rate (ESR) and plasma C3, C4, and C3d were measured and the SLE disease activity scored by a single observer. Serial data sets were analysed using time series modelling techniques. Single time point analysis showed a significant increase in urine neopterin concentrations in 14 patients who suffered flares of their disease during the study period (p = 0.02). Thirty patients with active disease went into disease remission with significant decreases in their urine neopterin values (p = 0.02). In the time series analysis, a statistically significant association was found between serial concentrations of urine neopterin and BILAG score (r = 0.6, p < 0.05); no other study parameter (ESR and serum C3, C4, and C3d) mirrored SLE disease activity as effectively. This study provides initial evidence that changes in urine concentrations of neopterin are significantly correlated with fluctuations in disease activity over time, scored using the BILAG index, amongst individual patients with SLE. Consequently, serial urine neopterin measurements appear to be clinically useful for monitoring disease activity and may contribute substantially to therapeutic decision making in these patients.

The BILAG index: a reliable and valid instrument for measuring clinical disease activity in systemic lupus erythematosus

The British Isles Lupus Assessment Group (BILAG) index is a computerized index for measuring clinical disease activity in systemic lupus erythematosus (SLE), which was developed according to the principle of the physician's 'intention to treat'. The index allocates separate alphabetic scores to each of eight organ-based systems; a total score is not calculated. This study demonstrated good between-rater reliability for the BILAG index for each organ-based system. There was no evidence of bias between observers. The BILAG index had good overall sensitivity (87%) and specificity (99%) when compared with the 'gold standard' criterion (starting or increasing disease-modifying therapy). There were high positive predictive values overall (80%), and for each organ-based system, with the exception of the neurological system.

Urine neopterin as a parameter of disease activity in patients with systemic lupus erythematosus: comparisons with serum sIL-2R and antibodies to dsDNA, erythrocyte sedimentation rate, and plasma C3, C4, and C3 degradation products.

OBJECTIVES--To investigate urine neopterin as a parameter of disease activity in an unselected group of patients with systemic lupus erythematosus (SLE) and to study the relation between urine neopterin and certain patterns of organ disease and differing drug regimens in the treatment of SLE. METHODS--Neopterin was determined by high performance liquid chromatography in 115 early morning urine samples from 68 patients with SLE. Serum soluble interleukin 2 receptor (sIL-2R) and antibodies to double stranded DNA (dsDNA) were determined by enzyme linked immunosorbent assay (ELISA), and the erythrocyte sedimentation rate (ESR), plasma C3, C4, and C3 degradation products (C3dg) were measured in corresponding blood samples. Disease activity was scored using the British Isles Lupus Assessment Group (BILAG) index. RESULTS--Urine neopterin was significantly increased in patients with active and inactive SLE compared with the control group and was significantly higher in patients with active than in those with inactive SLE. Urine neopterin did not distinguish between subsets of patients with SLE with particular patterns of organ disease, as defined by the BILAG index, nor was its level primarily influenced by differing drug regimens. Levels of serum sIL-2R, antibodies to dsDNA, the ESR, and plasma C3, C4, and C3dg were also significantly different between the patients with active and inactive SLE. Unlike urine neopterin there was considerable overlap in the values of these parameters between the two activity groups. Highly significant correlations found between urine neopterin and serum sIL-2R, ESR, and plasma C3, C4, and C3dg suggest the close association of neopterin with clinical activity in SLE. Multivariate logistic regression analysis showed that urine neopterin > 300 mumol/mol creatinine was a highly significant predictor of disease activity with an odds ratio of 3.51. CONCLUSIONS--Determination of urine neopterin, a non-invasive, relatively simple and inexpensive measurement, appears to be the best parameter for assessing and monitoring disease activity and treatment in patients with SLE.