Systemic Lupus Erythematosus Disease Manifestations Research Articles

Epitope-Specific Anti-C1q Autoantibodies in Systemic Lupus Erythematosus.

ObjectiveIn patients with systemic lupus erythematosus (SLE) complement C1q is frequently targeted by autoantibodies (anti-C1q), that correlate best with active renal disease. Anti-C1q bind to largely unknown epitopes on the collagen-like region (CLR) of this highly functional molecule. Here we aimed at exploring the role of epitope-specific anti-C1q in SLE patients.MethodsFirst, 22 sera of SLE patients, healthy controls and anti-C1q positive patients without SLE were screened for anti-C1q epitopes by a PEPperMAP® microarray, expressing CLR of C1q derived peptides with one amino acid (AA) shift in different lengths and conformations. Afterwards, samples of 378 SLE patients and 100 healthy blood donors were analyzed for antibodies against the identified epitopes by peptide-based ELISA. Relationships between peptide-specific autoantibodies and SLE disease manifestations were explored by logistic regression models.ResultsThe epitope mapping showed increased IgG binding to three peptides of the C1q A- and three of the C1q B-chain. In subsequent peptide-based ELISAs, SLE sera showed significantly higher binding to two N-terminally located C1q A-chain peptides than controls (p < 0.0001), but not to the other peptides. While anti-C1q were associated with a broad spectrum of disease manifestations, some of the peptide-antibodies were associated with selected disease manifestations, and antibodies against the N-terminal C1q A-chain showed a stronger discrimination between SLE and controls than conventional anti-C1q.ConclusionIn this large explorative study anti-C1q correlate with SLE overall disease activity. In contrast, peptide-antibodies are associated with specific aspects of the disease suggesting epitope-specific effects of anti-C1q in patients with SLE.

Tolerance of COVID-19 vaccination in patients with systemic lupus erythematosus: the international VACOLUP study.

Tolerance of COVID-19 vaccination in patients with systemic lupus erythematosus: the international VACOLUP study.

Pancreatitis in systemic lupus erythematosus: Clinical characterization and outcome analysis in concurrent pancreatitis and lupus

Objective: Pancreatitis in systemic lupus erythematosus (SLE) continues is an often under-diagnosed entity with high morbidity and mortality. The objective of this case series is to study the demographics and outcomes of lupus pancreatitis and to compare with available medical literature. Materials and Methods: Records of SLE patients admitted in our hospital between January 2012 and May 2018, were examined retrospectively. Clinical and laboratory parameters of the patients who were diagnosed with SLE and pancreatitis were obtained and analyzed. Results: The prevalence of pancreatitis in our cohort was 1.33% with 77% female preponderance. All the patients presented within 3 years of lupus onset. Pancreatitis was often associated with other disease manifestations of SLE and the mean Systemic Lupus Erythematosus Disease Activity Index 2K score at presentation was 17.4 ± 7.82. None of the patients were positive for APLA antibodies. All our patients were treated with high-dose steroids and other immunosuppression as indicated for concomitant disease activity. Complications were seen in only one patient who eventually succumbed to the disease. Conclusions: Pancreatitis in SLE is associated with disease activity. High index of suspicion, early diagnosis, and institution of steroids and immunosuppressive therapy lead to a good outcome.

Systemic Lupus Erythematosus: Symptoms and Signs at Initial Presentations.

Systemic Lupus Erythematosus (SLE) is an autoimmune multisystem inflammatory condition that causes microvascular inflammation with the production of various auto-antibodies that play a major role in its pathogenesis. SLE can affect both sexes, all ages, and all ethnic groups with widespread geographical and socioeconomic backgrounds. Asia encompasses people of many sociocultural backgrounds with diverse ethnic. Due to a lack of national epidemiological research, the incidence and prevalence of SLE in Middle Eastern and Arab countries, have only recently been studied. This article aims to explore the status of SLE in Oman and to record symptoms and signs of SLE at first presentation. Medical records of all patients diagnosed with SLE at the Royal Hospital from 2006 to 2014 were reviewed for information recorded at first visit. SLE diagnosis was based on the American College of Rheumatology classification criteria; ACR97 (which includes the clinical manifestation and laboratory evidence). Patients with SLE disease manifestations extrapolated and analyzed. There were 966 patients diagnosed with SLE during the period from 2006 to 2014. Mean (SD) age at presentations was 35.5 (11.5) years. Majority of patients were female which constitutes 88.7% of the total SLE patients with mean age 27.6 (1.4) years. Constitutional symptoms were found in 48.68 of SLE population including fatigue in 35.22%, and weight changes in 13.43%. The cutaneous manifestations that were present included malar rash 37.69%, photosensitivity 35.10%, discoid lupus 17.63%, and hair loss 39.29%. Musculoskeletal manifestations were commonly seen among the studied population including arthralgia in 68.75%, myalgia in 55.65%, arthritis in 48.31%, whilst myositis, tendon abnormalities and avascular necrosis were found in only 2.47%, 0.31% and 1.98%. respectively. This is the first study of the symptoms and signs at initial clinical presentation of SLE patients compared to other studies done regionally where most have focused on clinical manifestations during the progression course of SLE. SLE manifestations may be related to the differences in the genetic make-up of the patients who come from various ethnic groups despite similar geography or sociocultural background, or to referral bias, as some studies were performed in the nephrology units and others in the rheumatology units. There is a pressing need to establish a nationwide and regional collaboration to establish LUPUS and to put forward a strategic planning with each MOH to provide an easy and efficient report of SLE cases and provide various effective management for such a debilitating syndrome.

B-Cell-Attracting Chemokine CXCL13 As a Marker of Disease Activity in Systemic Lupus Erythematosus (SLE)

Abstract Background A correlation was detected between the chemokine CXC ligand 13 (CXCL13) and lupus nephritis, but there is no data recorded in the literature about a relationship with other disease manifestations in systemic lupus erythematosus (SLE). Therefore, we sought to investigate the relationship between CXCL13 and overall disease activity and other disease manifestations in SLE. Patients and Methods Fifty-seven SLE patients (51 female, 6 male) aged 18–60 years, fulfilling≥4 SLICC classification criteria for the classification of SLE, were enrolled in a cross-sectional study. Disease activity was scored using the SLE Disease Activity Index (SLEDAI) scoring system. The serological workup included routine lab investigations (full blood count, liver and kidney function tests, and urinalysis) as well as ESR, CRP, anti-ds DNA, C3, C4, 24-h urine protein, and creatinine clearance. Plasma CXCL13 levels were detected by ELISA. Results CXCL13 levels were elevated in active SLE patients. A significant positive correlation was found between the total score of SLEDAI and CXCL13 levels (r=0.547, p-value &lt;0.0001). A statistically significant difference was found regarding the mean CXCL13 levels between the patient groups (classified according to SLEDAI score) (inactive &lt;3, mild/moderate ≥3–12, severe ˃12) (p-value&lt;0.001). The anti-ds DNA antibody titre showed a significant positive correlation with CXCL13 levels (r=0.335, p-value&lt;0.05). The complement levels (C3, C4) showed a significant negative correlation with CXCL13 levels (p-value&lt;0.001). Also there was a significant positive correlation between 24-h urine protein and urinary casts and CXCL13 levels (p-value&lt;0.05). Conclusion Our study revealed elevated levels of serum CXCL13 in active SLE patients. We demonstrated a highly significant positive correlation between serum CXCL13 levels in active SLE patients and SLE disease activity, which supports the role of CXCL13 in the pathogenesis of SLE disease and its activity. Among the variants used in calculating the SLEDAI score, we detected significant relations between level of serum CXCL13 and each of total and extra-renal SLEDAI score.

Variations in the epidemiology of systemic lupus erythematosus in southern Sweden.

The epidemiology of systemic lupus erythematosus (SLE) within a defined region in southern Sweden was studied during the time period 1981-2006. Furthermore, whether the phenotypic expression of SLE changed during the study period was investigated. Patients with suspected SLE were retrieved from diagnosis registries, hospital records and central laboratory databases. All new cases of SLE in this region were identified using validated retrieval methods and observed prospectively in a structured follow-up program. SLE disease manifestations, including classification criteria, were followed over time. A total of 174 cases were diagnosed with SLE during 1981-2006. In the first period of the study, from 1981 to 1993, the incidence of SLE was 5.0/100,000 inhabitants and in the second period of the study, 1994-2006, the annual incidence decreased to 2.8/100,000. During the first period the highest incidence was among females between the ages of 45 and 54 years; 15.1/100,000 inhabitants, which was reduced in the second period to 3.8/100,000. During the second period the highest age and sex specific incidence was among women between 25 and 34 years (6.6/100,000 inhabitants). The point prevalence of SLE on 31 December 1993 was 55/100,000 inhabitants compared with 31 December 2006, when it was 65/100,000 inhabitants. The phenotype of the disease did not vary significantly during the study period. The incidence rate of SLE in younger females remained stable from 1981 to 2006. However, in middle-aged women the incidence was substantially reduced in the latter half of the study period.

SLE: Another Autoimmune Disorder Influenced by Microbes and Diet?

Systemic lupus erythematosus (SLE) is a multi-system autoimmune disease. Despite years of study, the etiology of SLE is still unclear. Both genetic and environmental factors have been implicated in the disease mechanisms. In the past decade, a growing body of evidence has indicated an important role of gut microbes in the development of autoimmune diseases, including type 1 diabetes, rheumatoid arthritis, and multiple sclerosis. However, such knowledge on SLE is little, though we have already known that environmental factors can trigger the development of lupus. Several recent studies have suggested that alterations of the gut microbial composition may be correlated with SLE disease manifestations, while the exact roles of either symbiotic or pathogenic microbes in this disease remain to be explored. Elucidation of the roles of gut microbes – as well as the roles of diet that can modulate the composition of gut microbes – in SLE will shed light on how this autoimmune disorder develops, and provide opportunities for improved biomarkers of the disease and the potential to probe new therapies. In this review, we aim to compile the available evidence on the contributions of diet and gut microbes to SLE occurrence and pathogenesis.

Specific systemic lupus erythematosus disease manifestations in the six months prior to conception are associated with similar disease manifestations during pregnancy.

Past studies have focused on aggregate lupus disease activity during pregnancy and have produced conflicting results. Our study evaluated lupus activity based on involvement of five specific organ systems during the six months prior to conception and during pregnancy. We assessed 147 pregnancies among 113 women followed at Brigham and Women's Lupus Center, 1990-2013. Organ-specific activity included hematologic disorder, nephritis, skin disease, arthritis, and serositis. We hypothesized that the presence of organ-specific activity six months prior to conception would increase the risk for that same type of activity during pregnancy. Our study population was 68% white; 100% had a positive ANA and 30% had a history of nephritis. Among women with organ-specific lupus activity during the six months before conception, the crude odds for the same type of activity during pregnancy was 7.7- to 32.5-fold higher compared to women without that type of activity immediately before conception. An adjusted logistic regression model also indicated significantly higher odds of organ-specific activity during pregnancy if that type of activity were present six months before conception. Approaching lupus based on specific organ systems may be a useful way for women and their physicians to consider the potential risk for disease activity during pregnancy.

Chance, genetics, and the heterogeneity of disease and pathogenesis in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a remarkably complex and heterogeneous systemic autoimmune disease. Disease complexity within individuals and heterogeneity among individuals, even genetically identical individuals, is driven by stochastic execution of a complex inherited program. Genome-wide association studies (GWAS) have progressively improved understanding of which genes are most critical to the potential for SLE and provided illuminating insight about the immune mechanisms that are engaged in SLE. What initiates expression of the genetic program to cause SLE within an individual and how that program is initiated remains poorly understood. If we extrapolate from all of the different experimental mouse models for SLE, we can begin to appreciate why SLE is so heterogeneous and consequently why prediction of disease outcome is so difficult. In this review, we critically evaluate extrinsic versus intrinsic cellular functions in the clearance and elimination of cellular debris and how dysfunction in that system may promote autoimmunity to nuclear antigens. We also examine several mouse models genetically prone to SLE either because of natural inheritance or inheritance of induced mutations to illustrate how different immune mechanisms may initiate autoimmunity and affect disease pathogenesis. Finally, we describe the heterogeneity of disease manifestations in SLE and discuss the mechanisms of disease pathogenesis with emphasis on glomerulonephritis. Particular attention is given to discussion of how anti-DNA autoantibody initiates experimental lupus nephritis (LN) in mice.

FRI0374 Outcomes in Systemic Lupus Erythematosus Patients with High Disease Activity Treated with Belimumab: 18 Month Results from the US Observe Study

BackgroundCertain baseline factors in the BLISS trials were associated with high disease activity and identified as predictors of improved belimumab response.ObjectivesWe examined clinical effectiveness of belimumab 10 mg/kg plus standard...

Differential microRNA Profile and Post-Transcriptional Regulation Exist in Systemic Lupus Erythematosus Patients with Distinct Autoantibody Specificities

Systemic lupus erythematosus (SLE) patients have anti-nuclear autoantibodies directed against dsDNA and RNA-associated antigens (extractable nuclear antigens; ENA). In this study, we investigated the differences in microRNA (miRNA) expression and its biological implications in SLE patients with distinct autoantibody specificities. The SLE patients were grouped into three subsets based on the type of autoantibodies present in their sera (anti- ENA+ group with autoantibodies against ENA alone; antidsDNA+ group having autoantibodies against dsDNA only, and anti-ENA+dsDNA+ group having autoantibodies to both dsDNA and ENA). Global miRNA expression profiling was done for each of these three groups using TaqMan® low density miRNA arrays. We report that different sets of miRNAs are dysregulated in SLE patients with different autoantibody specificities. Further, Ingenuity pathway analysis (IPA) software revealed specific biological pathways that were targeted by miRNAs dysregulated in different SLE subsets. Molecules involved in cell cycle and cytoskeleton remodeling were the prime targets of miRNAs dysregulated in anti-ENA+ patients whereas miRNAs dysregulated in anti-dsDNA+ patients were found to be implicated in multiple cytokine signaling pathways. IPA analysis of gene targets of miRNAs commonly dysregulated in all three SLE subsets identified several metabolic-, hormone-, and interferon-related pathways to be affected. The differential miRNA expression in patients with distinct autoantibodies is suggestive of different regulatory mechanisms operating among them. Based on these observations, we are hopeful that this 'sub-grouping' approach could be used to identify other defective processes associated with varying disease manifestations in SLE and may be considered when designing therapeutic interventions.

A3.26 Proteasome inhibition with bortezomib in refractory SLE inhibits type I interferon and depletes plasma cells but does not inhibit their regeneration

BackgroundThe proteasome inhibitor bortezomib, approved for the treatment of multiple myeloma, has been demonstrated to deplete short- and long-lived plasma cells (PCs) and ameliorate nephritis in murine models of systemic...

High sensitivity C-reactive protein (hsCRP): Association with clinical subsets in systemic lupus erythematosus (SLE) patients from Western India

BackgroundHigh-sensitivity C-reactive protein (hsCRP) is a marker of systemic inflammation. hsCRP have been related to disease presence and clinical activity in systemic lupus erythematosus (SLE). AimTo understand the association between hsCRP and SLE disease manifestations and other associated immune parameters. Material & methodsOne hundred and ten SLE patients were studied and SLE disease activity was evaluated by SLE Disease Activity Index (SLEDAI). Among these 42.7% patients had lupus nephritis (LN). hsCRP and complement levels were detected by nephelometer. ResultsA total of 40/110 (36.4%) had elevated hsCRP levels. High CRP was associated with presence of infection (p < 0.001) Patients having bacterial, parasitic and viral infections had elevated levels of hsCRP. LN patients showed slightly higher hsCRP levels (29.3 ± 29.9 mg/L than non-LN group (27.3 ± 21.3 mg/L) but this difference was not significant. Patients with raised hsCRP levels showed a higher prevalence of low complement levels as compared to patients with normal CRP levels (p = 0.03). ConclusionElevated hsCRP levels were found to be associated with infections in SLE patients and low complement levels. Elevated hsCRP levels can be used as a marker of active infection in SLE patients.

Oral administration of different forms of a tolerogenic peptide to define the preparations and doses that delay anti-DNA antibody production and nephritis and prolong survival in SLE-prone mice

Therapeutic agents currently in use to treat systemic lupus erythematosus (SLE) are predominantly immunosuppressive agents with limited specificities. Multiple groups, including ours, have illustrated that inducing tolerance in SLE animal models ameliorates disease symptoms and increases survival. We examined if oral administration of a tolerogenic peptide could affect SLE disease progression. The pConsensus (pCons) peptide, based on protein sequences of anti-double stranded (anti-ds)DNA antibodies, induces tolerance through upregulation of regulatory T cells when administered intravenously. Six different forms of pCons, including multiple antigenic peptides (MAP) and cyclic peptides made up of L- and D-amino acids, at three different concentrations, were fed to BWF1 SLE-susceptible mice for 30 weeks. Mice fed 100 µg of L-MAP or D-MAP had less cumulative proteinuria and serum anti-dsDNA antibody levels than controls. In addition, animals in these groups also survived significantly longer than controls with a corresponding increase in serum transforming growth factor beta (TGFβ, implying a protective role for pCons-induced regulatory T cells. Oral administration of a tolerogenic peptide is a safe, effective method for ameliorating SLE disease manifestations and prolonging survival in SLE-prone mice. Induction of oral tolerance using modified pCons peptides could lead to a novel targeted therapy for human SLE.

Avascular necrosis of bone in systemic lupus erythematosus

IntroductionAvascular necrosis (AVN) is a major cause of morbidity in SLE. Several factors have been associated with the development of osteonecrosis in SLE but corticosteroid therapy has been the most consistent. Many factors such as thromboembolism, fat embolism, thrombophilia, hypofibrinolysis, intramedullary haemorrhage, vasculitis and increased bone marrow pressure are related to corticosteroid-induced osteonecrosis. Aim of the workTo determine the prevalence of avascular necrosis (AVN) of bone in patients with systemic lupus erythematosus (SLE) and to study the predictive factors for AVN in patients with SLE and its association with other SLE disease manifestations. Patients and methodsOne hundred consecutive SLE patients, diagnosed according to the updated American College of Rheumatology criteria (ACR), were studied. A full medical history and rheumatologic examination were administered to all patients. Laboratory and serologic tests were also carried out. Systemic disease activity was scored using the systemic lupus erythematosus disease activity index (SLEDAI). Cases of symptomatic AVN were identified by plain X-ray and magnetic resonance imaging (MRI). Comparisons between groups of patients with and without AVN, and associations between groups were analyzed by the t-test, Pearson correlation as well as multiple regression models to study the predictive factors for AVN in patients with SLE. ResultsAVN was detected in 15% (n=15) of SLE patients. Osteonecrosis of one hip joint was highly predictor for the other (p=0.000). Cumulative corticosteroid dose, Gait disturbance, myalgia and hypertension are the clinical predictors of AVN (p=0.000, 0,000, 0.001, 0.000), respectively, in the regression analysis model. Haemoglobin and proteinuria were the laboratory predictive (p=0.000, 0.000), respectively. ConclusionsLupus patients are at high risk for avascular necrosis (AVN), this risk extended to those on high dose corticosteroid of which patient's screening should be considered and closely monitored by sensitive techniques such as MRI.

Interferon‐α treatment of female (NZW × BXSB)F1 mice mimics some but not all features associated with the Yaa mutation

Male (NZW x BXSB)F(1) mice develop antiphospholipid syndrome (APS) and proliferative glomerulonephritis that is markedly accelerated by the Yaa locus encoding an extra copy of Tlr7. Female (NZW x BXSB)F(1) mice with only 1 active copy of Tlr7 develop late-onset glomerulonephritis but not APS. Because a major function of Toll-like receptor 7 is to induce type I interferons (IFNs), our goal was to determine whether IFNalpha can induce or accelerate the manifestations of systemic lupus erythematosus (SLE) in female (NZW x BXSB)F(1) mice. Eight-week-old female (NZW x BXSB)F(1) mice were injected with a single dose of adenovirus expressing IFNalpha. Mice were monitored for the development of thrombocytopenia and proteinuria. Sera were tested for anticardiolipin and anti-Sm/RNP antibodies. Mice were killed at 17 or 22 weeks of age, and their kidneys and hearts were examined histologically and by immunohistochemistry. Spleen cells were phenotyped, and enzyme-linked immunospot assays for autoantibody-producing B cells were performed. IFNalpha markedly accelerated nephritis and death in female (NZW x BXSB)F(1) mice. A significant increase in spleen cell numbers associated with a striking increase in the number of activated B and T cells was observed. Marginal-zone B cells were retained. IFNalpha-induced increased titers of autoantibodies were observed, but thrombocytopenia was not observed. Cardiac damage was milder than that in male mice. IFNalpha accelerates the development of renal inflammatory disease in female (NZW x BXSB)F(1) mice but induces only mild APS and does not induce thrombocytopenia. The effect of IFNalpha on SLE disease manifestations is strain dependent. These findings are relevant to our understanding of the physiologic significance of the IFN signature.

Haplotypes of the HRES‐1 endogenous retrovirus are associated with development and disease manifestations of systemic lupus erythematosus

Endogenous retroviral sequences represent a link between viral and genetic factors that may influence the development of systemic lupus erythematosus (SLE). The HRES-1 human endogenous retroviral sequence is centrally located at the 1q42 chromosomal region relative to microsatellites previously associated with SLE. We therefore undertook the present study to determine the haplotypes of the HRES-1 locus and their linkage to SLE. One hundred six patients with SLE, 82 unrelated healthy Caucasian individuals, and 70 healthy members of 34 lupus families were examined. HRES-1 was amplified by polymerase chain reaction (PCR) and analyzed by sequencing and restriction enzyme mapping. Microsatellites were analyzed by PCR. Haplotype construction and transmission disequilibrium testing (TDT) were performed in lupus families. Based on 4 single-nucleotide polymorphisms (SNPs) within a 935-base interval, we detected 6 HRES-1 haplotypes that were differentially segregated in unrelated Caucasian patients and control subjects (chi(2) = 16.86, P = 0.0048) and were in linkage disequilibrium (LD) with the D1S225 microsatellite (P = 0.0002). The microsatellites D1S225, D1S235, and D1S2785 (but not D1S229) were linked to SLE by TDT. Interestingly, LD between HRES-1 SNPs at bases 653 and 1259 was reduced in patients with SLE (P = 0.048). The HRES-1 653C/1259C-harboring alleles were associated with the presence of renal disease (P = 0.0021) and with the absence of lung disease (P = 0.0323), while the 956A allele was associated with the antiphospholipid syndrome in patients with SLE (P = 0.0036). The HRES-1 locus represents a recombination hot spot at the 1q42 chromosomal region that influences the development and disease manifestations of SLE.

SLE, atherosclerosis and cardiovascular disease

Atherosclerosis is an inflammatory disease and the major cause of cardiovascular disease (CVD) in general. Atherosclerotic plaques are characterized by the presence of activated immune competent cells, but antigens and underlying mechanisms causing this immune activation are not well defined. During recent years and with improved treatment of acute disease manifestations, it has become clear that the risk of CVD is very high in a prototypic autoimmune disease, systemic lupus erythematosus (SLE). SLE-related CVD and atherosclerosis are important clinical problems but may in addition also shed light on how immune reactions are related to premature atherosclerosis and atherothrombosis. A combination of traditional and nontraditional risk factors, including dyslipidaemia (and to a varying degree hypertension, diabetes and smoking), inflammation, antiphospholipid antibodies (aPL) and lipid oxidation are related to CVD in SLE. Premature atherosclerosis in some form leading to atherothrombosis is likely to be a major underlying mechanism, though distinctive features if any, of SLE-related atherosclerosis when compared with 'normal' atherosclerosis are not clear. One interesting possibility is that factors such as inflammation or aPL make atherosclerotic lesions in autoimmune disease more prone to rupture than in 'normal' atherosclerosis. Whether premature atherosclerosis is a general feature of SLE or only affects a subgroup of patients remains to be demonstrated. Treatment of SLE patients should also include a close monitoring of traditional risk factors for CVD. In addition, attention should also be paid to nontraditional risk factors such as inflammation and SLE-related factors such as aPL. Hopefully novel therapeutic principles will be developed that target the causes of the inflammation and immune reactions present in atherosclerotic lesions.

Nonstandard and adjunctive medical therapies for systemic lupus erythematosus

Nonstandard and adjunctive medical therapies for systemic lupus erythematosus

Production of IL-1β, IL-1 Receptor Antagonist and IL-10 by Mononuclear Cells from Patients with SLE

Depositions of immune-complexes are responsible for many of the pathological features of systemic lupus erythematosus (SLE). For example, immune-complex-induced tissue damage in glomerulonephritis has been shown to be mediated, at least in part, by interleukin (IL)-1. Inappropriate production or function of IL-1 may therefore contribute to disease manifestations in SLE. We investigated lipopolysaccharide (LPS)- and adherent IgG-stimulated release of IL-1β, IL-1 receptor antagonist (IL-1ra) and IL-10, a potent modulator of IL-1, by blood mononuclear cells from patients with SLE. Mediator production was measured as ng cytokines/106 monocytes and compared with clinical parameters. Release of IL-1β was only detectable in LPS-stimulated cultures and substantially reduced in patients with both active and inactive disease (P < 0.001). LPS-stimulated IL-1ra release was normal and the IL-1ra/IL-1β ratio was therefore increased (P < 0.05) and correlated inversely to prednisolone dosage (P = 0.009). IgG-stimulated release of IL-1ra was reduced in patients with active disease compared to those with inactive disease and controls (P = 0.002). IL-10 release was similar in patients and controls. We conclude that monocytes from patients with active SLE are deficient in Fcγ-R-mediated production of IL-1ra, whereas LPS-stimulated IL-1β release by SLE monocytes is reduced regardless of disease activity. The former may contribute to immune-complex-mediated tissue damage in SLE.