Immunopathogenesis Of Systemic Lupus Erythematosus Research Articles

Type I interferon blockade with anifrolumab in patients with systemic lupus erythematosus modulates key immunopathological pathways in a gene expression and proteomic analysis of two phase 3 trials

IntroductionAnifrolumab is a type I interferon (IFN) receptor 1 (IFNAR1) blocking antibody approved for treating patients with systemic lupus erythematosus (SLE). Here, we investigated the immunomodulatory mechanisms of anifrolumab using...

Platelet TLR7 is essential for the formation of platelet-neutrophil complexes and low-density neutrophils in lupus nephritis.

Platelets and low-density neutrophils (LDNs) are major players in the immunopathogenesis of SLE. Despite evidence showing the importance of platelet-neutrophil complexes (PNCs) in inflammation, little is known about the relationship between LDNs and platelets in SLE. We sought to characterize the role of LDNs and Toll-like receptor 7 (TLR7) in clinical disease. Flow cytometry was used to immunophenotype LDNs from SLE patients and controls. The association of LDNs with organ damage was investigated in a cohort of 290 SLE patients. TLR7 mRNA expression was assessed in LDNs and high-density neutrophils (HDNs) using publicly available mRNA sequencing datasets and our own cohort using RT-PCR. The role of TLR7 in platelet binding was evaluated in platelet-HDN mixing studies using TLR7-deficient mice and Klinefelter syndrome patients. SLE patients with active disease have more LDNs, which are heterogeneous and more immature in patients with evidence of kidney dysfunction. LDNs are platelet bound, in contrast to HDNs. LDNs settle in the peripheral blood mononuclear cell (PBMC) layer due to the increased buoyancy and neutrophil degranulation from platelet binding. Mixing studies demonstrated that this PNC formation was dependent on platelet-TLR7 and that the association results in increased NETosis. The neutrophil:platelet ratio is a useful clinical correlate for LDNs, and a higher NPR is associated with past and current flares of LN. LDNs sediment in the upper PBMC fraction due to PNC formation, which is dependent on the expression of TLR7 in platelets. Collectively, our results reveal a novel TLR7-dependent crosstalk between platelets and neutrophils that may be an important therapeutic opportunity for LN.

Host-derived mannose glycans trigger a pathogenic γδ T cell/IL-17a axis in autoimmunity.

Autoimmune diseases are life-threatening disorders that cause increasing disability over time. Systemic lupus erythematosus (SLE) and other autoimmune diseases arise when immune stimuli override mechanisms of self-tolerance. Accumulating evidence has demonstrated that protein glycosylation is substantially altered in autoimmune disease development, but the mechanisms by which glycans trigger these autoreactive immune responses are still largely unclear. In this study, we found that presence of microbial-associated mannose structures at the surface of the kidney triggers the recognition of DC-SIGN-expressing γδ T cells, inducing a pathogenic interleukin-17a (IL-17a)-mediated autoimmune response. Mice lacking Mgat5, which have a higher abundance of mannose structures in the kidney, displayed increased γδ T cell infiltration into the kidney that was associated with spontaneous development of lupus in older mice. N-acetylglucosamine supplementation, which promoted biosynthesis of tolerogenic branched N-glycans in the kidney, was found to inhibit γδ T cell infiltration and control disease development. Together, this work reveals a mannose-γδ T cell-IL-17a axis in SLE immunopathogenesis and highlights glycometabolic reprogramming as a therapeutic strategy for autoimmune disease treatment.

Toll-like receptors 7 and 9 regulate the proliferation and differentiation of B cells in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune illness marked by the loss of immune tolerance and the production of autoantibodies against nucleic acids and other nuclear antigens (Ags). B lymphocytes are important in the immunopathogenesis of SLE. Multiple receptors control abnormal B-cell activation in SLE patients, including intrinsic Toll-like receptors (TLRs), B-cell receptors (BCRs), and cytokine receptors. The role of TLRs, notably TLR7 and TLR9, in the pathophysiology of SLE has been extensively explored in recent years. When endogenous or exogenous nucleic acid ligands are recognized by BCRs and internalized into B cells, they bind TLR7 or TLR9 to activate related signalling pathways and thus govern the proliferation and differentiation of B cells. Surprisingly, TLR7 and TLR9 appear to play opposing roles in SLE B cells, and the interaction between them is still poorly understood. In addition, other cells can enhance TLR signalling in B cells of SLE patients by releasing cytokines that accelerate the differentiation of B cells into plasma cells. Therefore, the delineation of how TLR7 and TLR9 regulate the abnormal activation of B cells in SLE may aid the understanding of the mechanisms of SLE and provide directions for TLR-targeted therapies for SLE.

Investigating the Role of T-bet+ B Cells (ABCs/DN) in the Immunopathogenesis of Systemic Lupus Erythematosus.

Age-associated B cells (ABCs) constitute a B cell subset, defined as CD19+CD21-CD11c+, that expands continuously with age and accumulates strongly in individuals with autoimmune and/or infectious diseases. In humans, ABCs are principally IgD-CD27- double-negative (DN) B cells. Data from murine models of autoimmunity, implicate ABCs/DN in the development of autoimmune disorders. T-bet, a transcription factor which is highly expressed in these cells, is considered to play a major role in various aspects of autoimmunity, such as the production of autoantibodies and the formation of spontaneous germinal centres. Despite the available data, the functional features of ABCs/DN and their exact role in the pathogenesis of autoimmunity remain elusive. This project focuses on the investigation of the role of ABCs/DN in the pathogenesis of systemic lupus erythematosus (SLE) in humans, as well as the effects that various pharmacological agents may have on these cells. Samples from patients with active SLE will be used to enumerate and immunophenotype - via flow cytometry - the ABCs/DN found in the peripheral blood of the patients. Transcriptomic analysis and functional assays for the cells, both before and after in vitro pharmacological treatments, will also be performed. The results of the study are expected to allow characterization of the pathogenetic role of ABCs/DN in SLE and could probably contribute, following careful association with the clinical state of the patients, towards the discovery and validation of novel prognostic and diagnostic markers of disease.

Expanding Roles of Noncoding RNAs in the Pathogenesis of Systemic Lupus Erythematosus.

The exact pathogenesis of systemic lupus erythematosus (SLE) remains unclear. Accumulating finds have indicated the roles of the non-coding RNAs (ncRNAs) acting as novel epigenetic regulatory elements in the dysfunction of the immune system in SLE. This review will introduce recent studies on how ncRNAs are involved in the development of SLE. Recent advances in ncRNAs biology have greatly expanded our understanding of epigenetic regulation of immune responses and inflammation, and increasing evidence suggests ncRNAs are important players in SLE development. Identifications of abnormal expression patterns of ncRNAs and relevant biological impacts in lupus patients have revealed their potential as novel biomarkers and therapeutic targets for SLE. The dysregulation of ncRNAs contributes to the immunopathogenesis of SLE. Clarifying the functions and mechanisms of SLE-associated ncRNAs provides new opportunities for disease biomarkers and targeted therapies.

Pathological relevance and treatment perspective of JAK targeting in systemic lupus erythematosus

ABSTRACT Introduction The pathogenesis of systemic lupus erythematosus (SLE) involves abnormalities in both acquired and innate immune system, which is mediated by numerous cytokines. Janus kinase (JAK) plays important roles in the signaling pathways of those cytokines and is an attractive therapeutic target for SLE. Currently, multiple clinical trials using JAK inhibitors with different selectivities for JAK family proteins are being conducted in SLE. Area covered In this article, we provide an overview of the pathological relevance of JAK and the clinical implications of JAK inhibitors in SLE based on recent reports. Expert opinion JAK inhibitors have the potential to modulate various immune networks through a variety of mechanisms, potentially regulating the complex immunopathogenesis in SLE. SLE is a clinically and immunologically heterogeneous disease; therefore, precision medicine is required to maximize the efficacy of JAK inhibitors. Further studies are needed to determine their risk-benefit ratio and selection of the most appropriate patients for JAK inhibitors.

Immunogenetic Relationship of HLA-G 14 bp Insertion/Deletion Polymorphism and Toll-Like Receptor 9 with Systemic Lupus Erythematosus in Egyptian Patients: A Case-Control Study.

IntroductionThe level of expression of the immunoregulatory human leukocyte antigen-G (HLA-G) has been suggested to play a role in the immunopathogenesis of systemic lupus erythematosus (SLE). A 14 bp insertion/deletion (ins/del) polymorphism in the 3ˊuntranslated region of HLA-G gene may influence the level of expression. The role of Toll-like receptor 9 (TLR9) in the pathogenesis of SLE has been highlighted. Data among Egyptian patients are quite limited.PurposeTo detect the association of HLA-G 14 bp ins/del gene polymorphism with the susceptibility to SLE and to correlate TLR9 serum level with disease activity among Egyptian patients.Patients and MethodsA case-control study that included 102 SLE female patients and 102 healthy matched volunteers as controls was carried out. Disease activity in patients was determined using the modified Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). HLA-G 14 bp ins/del genotype was detected by polymerase chain reaction (PCR). TLR9 serum level was estimated using enzyme-linked immunosorbent assay (ELISA) technique.ResultsThe ins/ins genotype was significantly increased among SLE patients compared to healthy subjects (58.8% vs 9.8%; odds ratio [OR] = 11.79, P < 0.001). The 14 bp ins allele was significantly more frequent in SLE patients than in healthy subjects (65.7% vs 27.9%, respectively) and significantly associated with an increased risk of SLE (OR 4.94, P < 0.001). The mean TLR9 serum level showed a significant increase in SLE patients compared to healthy subjects (397.04±137.86 vs 195.22±45.14 ng/L, p < 0.001) and was significantly associated with disease activity as well as to patients’ HLA-G genotypes (p < 0.001).ConclusionAmong Egyptian population, HLA-G 14 bp ins/ins homozygous genotype and ins allele may constitute a potential risk for SLE susceptibility, while TLR9 serum level is significantly associated with disease activity.

Clinical significance of interferon lambda-3 (IFNλ3)/interleukin 28B (IL28B) in systemic lupus erythematosus patients

BackgroundInappropriate and excessive activation of type I interferon (IFN) system is a key feature of systemic lupus erythematosus (SLE), and its targeting has led to important achievements in the development of novel drugs for SLE. Aim of the workTo evaluate the serum levels of interferon lambda IFNλ3 (IL28B) in Egyptian patients with SLE and investigate its potential relation with different clinical and laboratory parameters. Patients and methodsThe study included 40 SLE patients and 40 controls. The SLE disease activity index (SLEDAI) was assessed. The measurement of serum levels of IFNλ3 was performed in all participants using enzyme linked immunosorbent assay (ELISA). ResultsThe mean age of the patients was 26.8 ± 7.8 years with disease duration 5.1 ± 4.5 years and they were 35 females and 5 males. The serum levels of IFNλ3 were significantly higher in SLE patients (9.7 ± 12.47 pg/mL) compared to the control (5.13 ± 1.63 pg/mL)(p = 0.02). Significant correlations were observed between serum IFNλ3 and serositis (r = 0.35,p = 0.03), C3 consumption (r −0.33, p = 0.04) and SLEDAI (r 0.34, p = 0.03). On multivariate regression analysis, serositis and SLEDAI (but not C3) were significant independent predictors of IFNλ3 levels (β = 0.08, p = 0.037 and β = 0.06, p = 0.014 respectively). ConclusionThe results support a possible role of IFNλ3/IL28B in the immunopathogenesis of SLE. The significant association of serum IFNλ3 with disease activity highlights the utility of IFNλ3 as a novel biomarker for monitoring disease activity and predicting severity in SLE. Further studies on IFNλ3 in SLE could be promising in the development of personalized therapy for lupus patients.

New possibilities of pharmacotherapy for systemic lupus erythematosus: Prospects for the use of anifrolumab (monoclonal antibodies to type I interferon receptor)

Systemic lupus erythematosus (SLE) is a systemic autoimmune rheumatic disease of unknown etiology, characterized by overproduction of organ-specific autoantibodies to various components of the cell nucleus and the development of immune-inflammatory damage to internal organs. According to modern concepts, one of the key mechanisms of SLE immunopathogenesis is associated with dysregulation of type I interferon (IFN) synthesis The complex of data obtained in the process of fundamental and clinical research served as the basis for the development of a new approach to the pharmacotherapy of SLE, associated with the use of monoclonal antibodies (mAbs) that block the activity of IFN type I or its receptors. Among these drugs, anifrolumab (AFM) occupies a special place, which is a human IgG1 mAbs that bind to cellular receptors for IFN-α. The article discusses the materials of the main studies concerning the efficacy and safety of AFM in SLE, and the prospects for the use of this drug in the treatment of this disease.

Alternative Splicing: A New Cause and Potential Therapeutic Target in Autoimmune Disease.

Alternative splicing (AS) is a complex coordinated transcriptional regulatory mechanism. It affects nearly 95% of all protein-coding genes and occurs in nearly all human organs. Aberrant alternative splicing can lead to various neurological diseases and cancers and is responsible for aging, infection, inflammation, immune and metabolic disorders, and so on. Though aberrant alternative splicing events and their regulatory mechanisms are widely recognized, the association between autoimmune disease and alternative splicing has not been extensively examined. Autoimmune diseases are characterized by the loss of tolerance of the immune system towards self-antigens and organ-specific or systemic inflammation and subsequent tissue damage. In the present review, we summarized the most recent reports on splicing events that occur in the immunopathogenesis of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) and attempted to clarify the role that splicing events play in regulating autoimmune disease progression. We also identified the changes that occur in splicing factor expression. The foregoing information might improve our understanding of autoimmune diseases and help develop new diagnostic and therapeutic tools for them.

RNA receptors, TLR3 and TLR7, are potentially associated with SLE clinical features.

The influence of intracellular Toll-like-receptors (TLR), recognized as nucleic acid sensors, in the immunopathogenesis of systemic lupus erythematosus (SLE) is increasingly explored. Yet, the results of both functional and genetic studies remain conflictual. We evaluated the association between TLR3 and TLR7 genes selected variants and SLE and investigated the possible relationship with clinical and serological parameters. Then, we studied the genetic expression of these receptors, and if the TLR7 gene evades X chromosome inactivation (XCI). Our study covers 106 cases and 200 controls, genotyped using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. TLR3 and TLR7 expression level was assessed by qPCR carried, respectively, on renal tissues and PBMC, and methylation status was evaluated by methylation-specific PCR. Results were statistically analysed using Shesis software, χ2 , and Mann-Whitney test. Significant associations with SLE susceptibility were found for the TLR3 rs3775291, rs5743305 and rs3775294 polymorphisms. Further subgroup analysis, TLR3 rs3775291 and rs3775294 polymorphisms were significantly associated with lupus nephritis (LN) and even correlate with the presence of auto-antibodies binding RNA molecules. SLE and LN were more common in men with rs3853839-G variant within TLR7 gene versus those carrying the C allele. Moreover, the role of the G allele in the TLR7 expression up-regulation was confirmed. However, gene expression analysis showed no significant differences in TLR3 and TLR7 mRNA levels between LN patient biopsies and healthy tissues (p>.05). When comparing patients and controls, no statistical difference was observed in XCI pattern. Otherwise, notable associations were raised between TLR3 and TLR7 gene variants and clinical and serological lupus features pointing towards the role of genetic background in the physiopathogenesis of the disease.

B Cell Aberrance in Lupus: the Ringleader and the Solution.

Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease with high heterogeneity but the common characterization of numerous autoantibodies and systemic inflammation which lead to the damage of multiple organs. Aberrance of B cells plays a pivotal role in the immunopathogenesis of SLE via both antibody-dependent and antibody-independent manners. Escape of autoreactive B cells from the central and peripheral tolerance checkpoints, over-activation of B cells and their excessive cytokines release whichdrive T cells and dendritic cells stimulation, and dysregulated surface molecules, as well as intracellular signal pathways involved in B cell biology, are all contributing to B cell aberrance and participating in the pathogenesis of SLE. Based on that rationale, targeting aberrance of B cells and relevant molecules and pathways is expected to be a promising strategy for lupus control. Multiple approaches targeting B cells through different mechanisms have been attempted, including B-cell depletion via monoclonal antibodies against B-cell-specific molecules, blockade of B-cell survival and activation factors, suppressing T-B crosstalk by interrupting costimulatory molecules and inhibiting intracellular activation signaling cascade by targeting pathway molecules in B cells. Though most attempts ended in failure, the efficacy of B-cell targeting has been encouraged by the FDA approval of belimumab that blocks B cell-activating factor (BAFF) and the recommended use of anti-CD20 as a remedial therapy in refractory lupus. Still, quantities of clinical trials targeting B cells or relevant molecules are ongoing and some of them have displayed promising preliminary results. Additionally, advances in multi-omics studies help deepen our understandings of B cell biology in lupus and maypromote the discovery of novel potential therapeutic targets. The combination of real-world data with basic research achievements may pave the road to conquering lupus.

Interferon-directed therapies for the treatment of systemic lupus erythematosus: a critical update.

The interferon (IFN) pathway, especially type I IFN, plays a critical role in the immunopathogenesis of systemic lupus erythematosus (SLE). We have gained significant insights into this pathway over the past two decades, including a better understanding of the key mediators of inflammation upstream and downstream of type I IFN. This has led to the identification of multiple potential targets for the treatment of SLE, for which a significant unmet need remains due to the failure of many patients to adequately respond to standard-of-care medications. Unfortunately, most new therapies in SLE have disappointed in preclinical or clinical trials to date, including a number that target type I IFN. Nevertheless, several IFN-directed therapies aimed at specific steps within this immunologic pathway have recently shown promise, and additional agents are in the treatment pipeline. In this review, we focus on the results of key therapeutic studies targeting the type I IFN pathway and discuss the future state of IFN-blockade in SLE.

An Autoimmunogenic and Proinflammatory Profile Defined by the Gut Microbiota of Patients With Untreated Systemic Lupus Erythematosus.

Changes in gut microbiota have been linked to systemic lupus erythematosus (SLE), but knowledge is limited. Our study aimed to provide an in-depth understanding of the contribution of gut microbiota to the immunopathogenesis of SLE. Fecal metagenomes from 117 patients with untreated SLE and 52 SLE patients posttreatment were aligned with 115 matched healthy controls and analyzed by whole-genome profiling. For comparison, we assessed the fecal metagenome of MRL/lpr mice. The oral microbiota origin of the gut species that existed in SLE patients was documented by single-nucleotide polymorphism-based strain-level analyses. Functional validation assays were performed to demonstrate the molecular mimicry of newly found microbial peptides. Gut microbiota from individuals with SLE displayed significant differences in microbial composition and function compared to healthy controls. Certain species, including the Clostridium species ATCC BAA-442 as well as Atopobium rimae, Shuttleworthia satelles, Actinomyces massiliensis, Bacteroides fragilis, and Clostridium leptum, were enriched in SLE gut microbiota and reduced after treatment. Enhanced lipopolysaccharide biosynthesis aligned with reduced branched chain amino acid biosynthesis was observed in the gut of SLE patients. The findings in mice were consistent with our findings in human subjects. Interestingly, some species with an oral microbiota origin were enriched in the gut of SLE patients. Functional validation assays demonstrated the proinflammatory capacities of some microbial peptides derived from SLE-enriched species. This study provides detailed information on the microbiota of untreated patients with SLE, including their functional signatures, similarities with murine counterparts, oral origin, and the definition of autoantigen-mimicking peptides. Our data demonstrate that microbiome-altering approaches may offer valuable adjuvant therapies in SLE.

Aberrant Non-Coding RNA Expression in Patients with Systemic Lupus Erythematosus: Consequences for Immune Dysfunctions and Tissue Damage.

Systemic lupus erythematosus (SLE) is a complex systemic autoimmune disease with heterogeneous clinical manifestations. A diverse innate and adaptive immune dysregulation is involved in the immunopathogenesis of SLE. The dysregulation of immune-related cells may derive from the intricate interactions among genetic, epigenetic, environmental, and immunological factors. Of these contributing factors, non-coding RNAs (ncRNAs), including microRNAs (miRNAs, miRs), and long non-coding RNAs (lncRNAs) play critical roles in the post-transcriptional mRNA expression of cytokines, chemokines, and growth factors, which are essential for immune modulation. In the present review, we emphasize the roles of ncRNA expression in the immune-related cells and cell-free plasma, urine, and tissues contributing to the immunopathogenesis and tissue damage in SLE. In addition, the circular RNAs (circRNA) and their post-translational regulation of protein synthesis in SLE are also briefly described. We wish these critical reviews would be useful in the search for biomarkers/biosignatures and novel therapeutic strategies for SLE patients in the future.

New treatments for systemic lupus erythematosus

Improved understanding of the immunopathogenesis of systemic lupus erythematosus (SLE) has paved the way for new selective treatment strategies for these inflammatory systemic diseases, similarly to diseases such as rheumatoid arthritis and the spondylarthritides. New specific biologics were developed or are being developed and open up new treatment options for patients. Belimumab is particularly important in this respect. The monoclonal antibody that blocks the cytokine BAFF/BLyS is the first medicament approved for the treatment of serologically active SLE in the last decade and also the first biologic approved for this disease. Anumber of other biologics for the treatment of SLE are in clinical development. This article addresses the promising new drugs currently under development for the treatment of SLE.

High interleukin-18 and low FOXP3 mRNAs in peripheral blood of women with severe systemic lupus erythematosus: a cross-sectional study.

Gene expression analysis of peripheral blood cells may provide valuable information about the triggered molecular processes in systemic lupus erythematosus (SLE). The study aimed to quantify the mRNA in peripheral blood of seven target genes, including inflammatory cytokine genes (IL23A, IL12B, TNFA, IL18), and T regulatory-related genes (FOXP3, TGFB1, IL10) in patients with SLE and to correlate expression levels with disease activity and/or clinical manifestations. The relative quantification of target genes was performed using real-time polymerase chain reaction in peripheral blood obtained from 28 adult SLE females and 17 healthy women. The highest up-regulation in the blood of SLE patients was observed for IL23A with a median 9.54 (p < 0.0001), followed by TGFB1 (median: 2.07; p = 0.047) and IL10 (median: 1.84; p = 0.013). IL12B and TNFA were significantly down-regulated in patients compared to controls (median: 0.521; p = 0.0023, and median: 0.519; p = 0.0003, respectively). FOXP3 mRNA was lower among patients with higher degree of disease activity (median: 0.338; p = 0.029) and showed inverse correlation with Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). IL18 mRNA correlated positively with the SLEDAI and was highly expressed during severe flares (median: 1.216; p = 0.021). IL18 up-regulation was associated with anti-dsDNA antibody positivity, while FOXP3 down-regulation with lupus nephritis. Our study pointed out the relationship of SLE disease activity and particular clinical manifestations with IL18 and FOXP3 expression, and the significant contribution of IL23A in the SLE immunopathogenesis. Hence, the peripheral blood cytokine mRNAs should be exploited as novel prognostic and diagnostic biomarkers.

Systemic lupus erythematosus: new horizons for diagnosis and therapy

Systemic lupus erythematosus (SLE) is a systemic autoimmune rheumatic disease of unknown etiology, characterized by the overproduction of organ-specific autoantibodies to various components of the cell nucleus and by the development of immune-mediated inflammatory damage to internal organs. SLE is the prototype of a systemic human autoimmune disease; it is an extremely heterogeneous disease in terms of both clinical manifestations and a genetic predisposition and pathogenetic mechanisms, which often complicates the early diagnosis of the diseases and makes it impossible to personify therapy. Despite the fact that in the 21st century, the 15-year survival rate for SLE has increased up to 85%, the inadequate control of disease activity and the need for almost constant intake of glucocorticoids and immunosuppressive drugs result in the accrual of irreversible damages to internal organs and, as a consequence, in decreases in quality of life, disability, social maladaptation, and premature death. The paper considers the new 2019 EULAR/ACR diagnostic criteria for SLE, the contemporary 2019 EULAR recommendations for the management of SLE, and new pharmacotherapy options for this condition, which are based on the deciphering of the mechanisms of SLE immunopathogenesis.

Correlation between serum interleukin-6 with glomerular filtration rate in systemic lupus erythematosus

Background: Systemic lupus erythematosus (SLE) is characterized by remarkable heterogeneity in clinical manifestations with underlying autoimmune mechanisms. The pleiotropic cytokine interleukin-6 (IL-6) is known to be involved in SLE immunopathogenesis and significantly related to disease activity as well as its complications. Additionally, IL-6 has been demonstrated to underlie important roles in lupus nephritis.&#x0D; Objective: To determine the correlation between Interleukin 6 (IL-6) Serum and Glomelular Filtration Rate (GFR) in SLE.&#x0D; Methods: In this study we investigated the correlation of serum IL-6 with glomerular filtration rate (GFR) to assess kidney damage in 67 premenopausal patients aged between 17-50 years with inactive SLE. The study variables including age, duration of illness, cumulative corticosteroid dose, MEX-SLEDAI score, serum creatinine, and GFR were obtained through interview and medical record review; whilst serum level of IL-6 was measured using ELISA.&#x0D; Results: Median level of IL-6 was found to be 2.71 (0.332-10.000) pg/ml. Pearson correlation test showed significant correlation between serum IL-6 and GFR (r = 0.288, P = 0.018).&#x0D; Conclusion: This study result shows that there was positive correlation observed between serum IL-6 and GFR in inactive SLE.