Lupus Research Articles

Neuropilin-1 as a Key Molecule for Renal Recovery in Lupus Nephritis: Insights from an NZB/W F1 Mouse Model.

Systemic lupus erythematosus (SLE) is an autoimmune disease affecting multiple organs, with lupus nephritis (LN) occurring in 40-50% of SLE patients. Despite advances in diagnosis and treatment, LN remains a major cause of morbidity and mortality, with 10-20% of patients progressing to end-stage renal disease (ESRD). While knowledge of LN's pathogenesis has improved, mechanisms of renal recovery are still largely unexplored. Neuropilin-1 (NRP-1), a transmembrane receptor expressed in renal tissue, has emerged as a promising biomarker for assessing renal recovery in LN. This study evaluates and correlates longitudinal levels of NRP-1 with kidney histology using an NZB/W F1 mouse model of LN. A total of 30 mice were used, with 15 receiving intravenous cyclophosphamide (CYC) and 15 being untreated. NRP-1 levels were measured in urine and serum, and kidney samples were taken from a subgroup of mice for histological evaluation. The results demonstrated a progressive increase in renal and urinary NRP-1 expression, particularly notable at weeks 26 and 32. Urinary NRP-1 levels above 34.40 ng/mL were strong predictors of favorable renal response, showing 100% sensitivity and 88% specificity. These findings indicate a robust correlation between urinary NRP-1 levels and renal histological recovery, underscoring the potential of NRP-1 as a valuable biomarker for assessing renal response in LN. This study demonstrates that renal production of NRP-1 is linked to histological recovery and establishes a foundation for future research into the role of NRP-1 in lupus kidney recovery.

Young Girl with Weight loss, Prostration and Extreme Fatigue

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease that can affect multiple organ systems, particularly the kidneys, blood cells, skin, and musculoskeletal system. This report presents a case of a 16-year-old female diagnosed with lupus presenting with major organ involvement.

Ocular Manifestations In Patients With Systemic Lupus Erythematosus

Ocular Manifestations In Patients With Systemic Lupus Erythematosus

Efficacy and Safety of Sodium-Glucose Co-Transporter 2 Inhibitors for the Primary Prevention of Cardiovascular, Renal Events and Safety Outcomes in Patients with Systemic Lupus Erythematosus and Comorbid Type 2 Diabetes: A Population-based Target Trial Emulation.

Patients with systemic lupus erythematosus (SLE) were excluded from sodium-glucose co-transporter 2 inhibitors (SGLT2i) clinical trials. It is unknown whether the cardiorenal benefits of SGLT2i extend to patients with SLE and comorbid type 2 diabetes (T2D). We performed an emulated clinical trial in an insurance-based cohort in the U.S., evaluating SGLT2i versus dipeptidyl peptidase 4 inhibitors (DPP4i) for primary prevention of cardiovascular, renal, and other clinical outcomes among patients with both SLE patients and comorbid T2D. SGLT2i initiators were matched to DPP4i initiators using propensity scores (PS) based on clinical and demographic factors. Hazard ratios (HR with 95% confidence intervals) were calculated using Cox models. Outcomes among 2,165 patients starting SGLT2i and 2,165 PS-matched patients starting DPP4i were compared. Over 753.1 (±479.2) mean days, SGLT2i recipients had significantly lower risks of incident acute kidney injury (HR 0.49, 95% CI 0.39-0.63), chronic kidney disease (HR 0.61, 0.50-0.76), end-stage renal disease (HR 0.40, 0.20-0.80), heart failure (HR 0.72, 0.56-0.92), and emergency department visits (HR 0.90, 0.82-0.99). Risks of all-cause mortality (HR 0.89, 0.65-1.21), lupus nephritis (HR 0.67, 0.38-1.15), myocardial infarction (HR 0.81, 0.54-1.23), stroke (HR 1.03, 0.74-1.44), and hospitalizations (HR 0.76, 0.51-1.12) did not differ. Genital infection risk (HR 1.31, 1.07-1.61) was increased, but urinary tract infection risk (HR 0.90, 0.79-1.03) did not differ. No significant difference was observed for diabetic ketoacidosis risk (HR 1.065, 0.53-2.14) and fractures (HR 0.95, 0.66-1.36). In this emulated clinical trial, SGLT2i vs. DPP4i use was associated with significantly reduced risks of several cardiorenal complications among patients with both SLE and T2D.

Epigenetic regulation of FOXP3 gene expression in relation to impaired function of regulatory T cells in systemic lupus erythematosus

The impaired function of regulatory T (Treg) cells and the imbalance of Treg/Th17 cells play a central role in developing autoimmune diseases such as systemic lupus erythematosus (SLE). Treg cells are crucial for maintaining immune homeostasis and tolerance to self-antigens. One of the most important transcription factors that regulate the differentiation and function of Treg cells is the FOXP3 protein. Aberrant epigenetic modifications affecting FOXP3 gene expression and consequently dysregulated function of Treg cells have been implicated in the pathogenesis of SLE. Therefore, understanding the intricate interplay between FOXP3 expression pattern in Treg cells and epigenetic regulatory mechanisms (e.g., DNA methylation, histone modifications and non-coding RNAs such as microRNAs and long non-coding RNAs) is crucial for unravelling the underlying mechanisms of SLE. Moreover, targeting these epigenetic pathways may offer novel therapeutic strategies for restoring immune balance and ameliorating autoimmune pathology. This review report aimed to provide an update on the epigenetic controlling of FOXP3 gene expression in SLE disease.

Antimalarials in Lupus Nephritis: How Strong is the Evidence?

Systemic lupus erythematosus is a chronic multisystem autoimmune disease that affects the kidneys in approximately 50% of patients, with prevalence rising to as high as 70% in certain populations, such as African Americans and Asians. Antimalarials -and particularly hydroxychloroquine- are currently considered a mainstay of therapy, together with immunosuppressants. Over the last decades, several studies have extensively investigated the mechanisms of action of antimalarial agents, and their potential beneficial properties in patients with SLE in general. However, the evidence for the therapeutic benefit of hydroxychloroquine in patients with lupus nephritis (LN) derives mainly from observational studies, conducted in an era prior to the refinement of induction and maintenance protocols for immunosuppressive therapy. Despite the paucity of high-quality evidence on its efficacy in LN, the nephrology community widely supports the universal use of hydroxychloroquine in LN patients, and recommendations for its use are firmly entrenched in various clinical practice guidelines. Nonetheless, the use of antimalarials may also carry inherent risks, underscoring the importance of personalized approaches in these patients. Herein, we comprehensively review the available literature on antimalarials in LN aiming to update the current evidence, limitations, and future perspectives for the use of antimalarials in adults.

Clinical relevance and frequency of cytoplasmic patterns observed in ANA-Hep-2: experience of Cairo University Hospitals.

Antinuclear antibodies (ANA) are the most common biomarkers observed in autoimmune diseases. Cytoplasmic staining patterns on ANA-Hep-2 are gaining recognition but with scanty information about their clinical and diagnostic role. The aim is to assess the frequency of cytoplasmic ANA patterns in autoimmune diseases, and to evaluate their possible associations with clinical diagnoses and autoantibodies. This observational cross-sectional study was conducted by examining and/or reviewing ANA by indirect immunofluorescence assay during a 13-month period. This was followed by testing the group of patients with a positive cytoplasmic staining pattern (n = 92) using the Microblot-Array ANA plus for the presence of 44 specific autoantibodies. Out of 2741 samples, 1791 (65.3%) tested negative, 845 (30.9%) tested positive nuclear staining patterns, 56 (2.0%) positive solitary cytoplasmic staining patterns, and 49 (1.8%) positive mixed nuclear and cytoplasmic patterns. Ninety-two cases (3.4% of the total cases) were analyzed using Microblot-Array ANA plus, with reticular as the most frequent cytoplasmic pattern, followed by dense fine speckled. The most frequently associated disease with reticular pattern was primary biliary cholangitis (28.9%), and the most frequently detected autoantibodies were against M2 (66.7%). The most frequently associated disease with dense fine speckled pattern was systemic lupus erythematosus (69.4%), and the most frequently detected autoantibodies were against nucleosome (57.7%) and ribosomal P0 (53.8%). This study highlights the significance of reporting cytoplasmic staining patterns and their importance in assessment of autoimmune diseases. Larger cohort studies on treatment naïve patients are recommended.

Health-Related Quality of Life in Systemic Lupus Erythematosus and Its Relationship With Disease Activity: A Single-Center Cross-Sectional Study From Pakistan

Health-Related Quality of Life in Systemic Lupus Erythematosus and Its Relationship With Disease Activity: A Single-Center Cross-Sectional Study From Pakistan

Long-term outcome of tacrolimus-based immunosuppressive treatment for patients with paediatric-onset lupus nephritis.

We have previously reported the mid-term efficacy and safety of tacrolimus (Tac)-based immunosuppressive therapy in such patients, and herein, we aimed to determine their long-term outcomes (over 10 years). We retrospectively evaluate the data of 13 consecutive patients with biopsy-proven long-standing LN who underwent a long-term Tac-based treatment regimen. Tac was administered once daily at a dose of 3 mg as reinduction or maintenance treatment. Treatment outcomes were defined using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), urinary protein/creatinine ratio (Up/cr), serum creatinine, estimated glomerular filtration rate (eGFR) and serological lupus markers (complement C3, complement hemolytic activity [CH 50], and anti-dsDNA antibody titre), and the concomitantly administered prednisolone (PDN) dose. Data on clinical parameters and serological lupus activity were collected annually from each patient throughout the study period. The patients' baseline characteristics at the treatment initiation were as follows: mean age, 18 years; Up/cr, 0.63 ± 0.69; serum C3 level, 57.2 ± 22.4 mg/dL (normal range, 79-152 mg/dL); CH50, 27.9 ± 15.7 U/mL (normal range, 23.0-46.0 U/mL); serum anti-dsDNA antibody titre, 111.7 ± 123.4 IU/mL (normal range, <12.0 IU/mL); serum creatinine, 0.60 ± 0.19 mg/dL; eGFR, 115.6 ± 21.3 mL/min and SLEDAI, 13 ± 8.1. Despite the gradual tapering of the concomitantly administered PDN dose from 18.7 ± 13.5 mg/day at baseline to 3.5 ± 2.8 mg/day at 10 years (p = .002), a marked improvement in the outcomes, compared with the baseline values, was observed within a year. Additionally, these favourable changes persisted throughout study period in most patients. Compared with the baseline values, the following measures confirmed sustained outcome improvements after a 10-year treatment: SLEDAI, 1.7 ± 2.0; serum C3 level, 83.8 ± 16.1 mg/dL; CH50, 45.6 ± 10.9 U/mL (all p < .01) and Up/cr, 0.16 ± 0.18 and serum anti-dsDNA antibody titre, 25.8 ± 28.8 IU/mL (both p < .05). Serum creatinine level and eGFR remained within the normal range in all study participants except for one patient who experienced several flare-ups. No serious adverse effects were observed. Our results suggest that long-term Tac-based immunosuppressive treatment as maintenance therapy is beneficial and has low cytotoxicity. Therefore, it represents an attractive option for the treatment of selected patients with paediatric-onset LN in a real-world setting.

Drug-Induced Systemic Lupus Erythematosus: A Rare Presentation of Hydralazine-Induced Lupus

Drug-Induced Systemic Lupus Erythematosus: A Rare Presentation of Hydralazine-Induced Lupus

LncRNA NRIR serves as a biomarker for systemic lupus erythematosus and participates in the disease progression.

Systemic lupus erythematosus (SLE) is a complex autoimmune disorder characterized by a malfunction of the body's immune defense system. The objective of the present investigation was to examine the expression and diagnostic significance of NRIR in SLE and to prove whether it is involved in the progression of SLE. The study involved 110 participants, including 55 healthy individuals and 55 SLE patients. The expression levels of NRIR, miR-31-5p, and ICAM-1 were measured using qRT-PCR. The ROC curve was performed to assess the diagnostic significance of NRIR in SLE patients. Pearson correlation analysis was utilized to explore the relationship between NRIR and other indicators. Cytokines including IL-4, IL-6, and IL-21, along with IgG levels, were assessed using ELISA. The interaction between NRIR and miR-31-5p was validated using a dual-luciferase reporter assay. Upregulated expression of NRIR was observed in individuals with SLE, serving a diagnostic function for SLE. Additionally, abnormal expression of NRIR impacted the viability of CD4+ T cells within SLE patients. NRIR could negatively modulate the expression of miR-31-5p. LncRNA NRIR may be a potential biomarker for SLE and is likely involved in the progression of SLE.

Antiphospholipid Antibodies as Key Players in Systemic Lupus Erythematosus: The Relationship with Cytokines and Immune Dysregulation.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by an overproduction of cytokines, such as interleukins and interferons, contributing to systemic inflammation and tissue damage. Antiphospholipid syndrome is a thrombo-inflammatory autoimmune disease affecting a third of SLE patients. We performed an in-depth analysis of the available literature, and we highlighted the complex interplay between immunity, inflammation, and thrombosis, the three major pathogenic pathways that are trapped in a mutually reinforcing destructive loop.

The frequency of fibromyalgia in patients with systemic lupus erythematosus and associated factors: a systematic review and meta-analysis.

Fibromyalgia (FM) in systemic lupus erythematosus (SLE) patients contributes to increased fatigue, anxiety, depression, and mental exhaustion. This study's objective is to systematically review the literature and to determine the frequency of FM in patients with SLE and its associated factors. A literature review was conducted to assess the prevalence of FM in SLE patients and to identify FM-associated factors. This involved searching the PubMed and Cochrane Library databases from 1959 to 2023. Cohorts, case-control, and population-based studies were included, while those not focusing on FM rates in SLE patients were excluded. Data on FM-associated factors and FM frequency in control or connective tissue disease (CTD) groups were obtained if available. Secondary analyses compared FM frequencies in SLE and other groups (healthy controls or CTD groups). Fifty-six studies met the eligibility criteria. Out of the 56 studies, nine included comparative data between SLE patients and healthy controls, while six presented data comparing the frequency of FM in patients with SLE and other CTDs. The combined cohorts included 58,052 SLE patients. Among 5063 SLE patients, FM was detected. The overall random-effects pooled prevalence of FM was 15.8% (95% CI, 13.4-18.5) with high heterogeneity (I2, 97.9%). Our analysis revealed a significantly higher risk of FM in patients with SLE compared to controls (OR, 3.7; 95% CI, 2.74-5.0). There was a higher risk of FM in SLE patients compared to other rheumatic diseases, but the difference was not significant. Our study showed that the prevalence of FM is higher in patients with SLE compared to the general population. FM in SLE may act as a confounding factor when assessing disease activity and treatment response. Research results indicate that concurrent FM is a frequent comorbidity in SLE, emphasizing the importance of recognizing its occurrence in SLE patients.

Is Idiopathic Granulomatous Mastitis a Subgroup of Systemic Lupus Erythematosus? A Preliminary Study

Objective: The study aimed to use the systemic lupus erythematosus risk probability index (SLERPI) to assess if patients with idiopathic granulomatous mastitis (IGM) meet the criteria for systemic lupus erythematosus (SLE). Methods: A total of 62 patients with IGM and 55 age- and sex-matched healthy controls (HC) were enrolled. The study included patients who were over 18 years old and had been diagnosed with IGM using a true-cut biopsy. The participants’ demographic, clinical, and laboratory data were recorded in detail. The presence of autoantibodies, such as RF, CCP, C3, C4, ANA, ENA profile, and Anti-dsDNA was documented. For the detection of SLE in IGM patients, we used the SLERPI (SLE risk probability index). Results: A total of 62 patients diagnosed with idiopathic granulomatous mastitis (age 35.22 ± 8.34, BMI 27.15 ± 3.41) were compared to 55 healthy controls (age 32.54 ± 8.67, BMI 26.97 ± 3.54). The present study assessed the performance of SLERPI in IGM, and SLERPI positivity was observed in 12 out of 62 (19.4%) IGM patients. There was a significant difference in arthritis and ANA levels in the SLERPI subgroups (p &lt; 001). Conclusions: The SLERPI index can be utilized to identify patients suspected of having systemic lupus erythematosus (SLE) in the IGM cohort.

Immunoregulatory role of AC007278.3 and HOTAIR long non-coding RNAs in lupus nephritis: potential biomarkers and therapeutic targets.

Long non-coding RNAs (lncRNAs) have emerged as crucial regulators in various biological processes, including immune regulation and autoimmune pathologies. However, their specific significance in modulating the cytokine network in systemic lupus erythematosus (SLE) remains largely unexplored. This study assessed the expression patterns of immune-related lncRNAs, HOTAIR, and AC007278.3, along with their related protein-coding genes, TNF-α and IL18RAP, in nephritic SLE patients. Additionally, the potential of selected genes as diagnostic biomarkers for SLE was evaluated. Blood samples were obtained from SLE patients (n = 30) and age-sex-matched healthy controls (HCs) (n = 60). Subsequently, RNA was isolated from peripheral blood mononuclear cells (PBMCs), and cDNA was synthesized to analyze the expression levels of the target genes using real-time PCR. The correlation analysis between the relative expressions of different genes was examined in both the patient and HC groups. The diagnostic potential of the lncRNAs was determined by calculating the Area Under the Curve of the Receiver Operating Characteristics (AUC of ROC), Cut-off, sensitivity, and specificity. Our results indicated a significant upregulation of lncRNAs AC007278.3 (fold change [FC] = 14.13, p-value < 0.0001) and HOTAIR (FC = 14.1, p-value < 0.0001). Correspondingly, their associated target genes, TNF-α and IL18RAP, were also overexpressed in patients (FC = 2.66 and FC = 5.18, respectively, p-value < 0.001). Notably, a strong positive correlation was observed between IL18RAP and AC007278.3 in SLE patients. Moreover, the AUC of ROC analyses underscored the diagnostic efficacy of AC007278.3 alone and combined with HOTAIR, yielding values of 0.89 and 0.86, respectively. These findings highlight the potential immunoregulatory roles of lncRNAs AC007278.3 and HOTAIR, emphasizing their significance as promising diagnostic biomarkers and potential therapeutic targets for SLE. Additionally, they provide valuable insights into the molecular mechanisms underpinning the disease's pathogenesis.

Pharmacoeconomic analysis of rituximab and belimumab therapy in patients with systemic lupus erythematosus

The progressive course of systemic lupus erythematosus (SLE) with high activity and severe internal organs involvement requires the prescription of expensive biologic disease-modifying antirheumatic drugs (bDMARDs), rituximab (RTM) and belimumab (BLM), whose comparative clinical and economic efficacy has not been adequately studied.Objective: to evaluate the clinical and economic efficacy of RTM and BLM therapy in patients with SLE.Material and methods. The study included 50 SLE patients who were divided into two groups and received RTM (group 1, n=25) or BLM (group 2, n=25) therapy for 12 months. The clinical and economic analysis was performed with the cost-effectiveness method using the cost-per-responder (CPR) model. A clinically significant improvement in SLEDAI-2K (Systemic Lupus Erythematosus Disease Activity Index modified 2K; Δ ≥4) was considered a response to therapy. Direct and indirect costs were considered in the analysis.Results and discussion. Against a background of therapy, there was a decrease in SLE activity with a decrease in median SLEDAI-2K in group 1 from 12 [10.5; 18] to 8 [4; 10] and in group 2 from 10 [8; 14.5] to 4 [2; 4] (p&lt; 0.001 in both cases). A clinically significant improvement was observed in 56% of patients in group 1 and 72% of patients in group 2. The peculiarities of the BLM dosing regimen caused higher (1.7 times) total costs than in the case of RTM. According to the CPR value, RTM showed a greater benefit (1.3 times) than BLM (954 thousand rubles versus 1.25 million rubles). The incremental cost-effectiveness ratio (ICER) was 1.4 million rubles, which does not exceed the threshold of willingness to pay for a domestic patient.Conclusion. When comparing BLM and RTM therapy for SLE patients in real-life clinical practice, greater clinical and economic efficiency was demonstrated for RTM. BLM therapy was found to be “cost-effective”.

Ponatinib exacerbate renal injury in systemic lupus erythematosus mouse model through PDGFR-PI3K/AKT pathway

Lupus nephritis (LN) is a common clinical complication of systemic lupus erythematosus (SLE). Proliferative lupus nephritis represents the gravest form of LN, and since effective drugs for its treatment are still lacking, tyrosine kinase inhibitors (TKIs) find extensive clinical utility due to their notable impact on suppressing cell proliferation and may serve as potential drugs for LN treatment. However, previous studies on the effects of TKI on LN have been controversial. Ponatinib, a third-generation TKI, lacks studies on its role in LN. This study aimed to investigate the impact of the ponatinib on LN. MRL/lpr mice were evaluated for renal function, autoimmune markers and histopathological changes after oral administration of ponatinib. RNA-seq analysis was performed to explore the molecular pathways involved in ponatinib-induced kidney injury. Ponatinib uniquely exacerbated renal damage in MRL/lpr mice, evidenced by a decline in renal function and acute pathological changes, without affecting lupus-related autoimmune markers. Differential expressed genes analysis and functional enrichment implicate ponatinib-induced renal damage in MRL/lpr mice associated with adiponectin. Furthermore, we verified ponatinib signaling the PI3K/AKT pathway through PDGFRα, potentially influencing high molecular weight adiponectin (HMW ADIPOQ) expression and exacerbating renal damage. In conclusion, this study demonstrates that ponatinib can up-regulate HMW ADIPOQ expression via the PI3K/AKT pathway by inhibiting PDGFRα phosphorylation, highlighting the potential nephrotoxic effects of ponatinib in lupus-prone mice, and underscoring the importance of monitoring renal function in systemic autoimmune diseases patients receiving ponatinib.

Serum 25 Hydroxy – D in Patients without Vitamin D Supplementation: Perspectives from Cohorts with Rheumatoid Arthritis and Systemic Lupus Erythematosus

Hypovitaminosis D is common in the sunny UAE. This study focusses on the perspectives of 25 hydroxy-D in patients with RA and others with SLE ((Autoimmune disease, ADs)) and to compare them to others of patients without ADs) .The latter were used as control group. All included individuals were without history of vitamin D intake. Hypovitaminosis D was common in the 3 groups (RA, SLE and controls). However, the prevalence of hypovitaminosis D in patients with each of ADs was significantly lower to that of the control group yet with higher means of 25 (OH) D levels. These findings were in contrast to those of number of regional and international studies conducted earlier. Data on the high prevalence of hypovitaminosis D and the low mean values of 25 (OH) D were comparable between the two groups of ADs. Overall, the results of this study may lead to some controversy or perhaps a challenge to the widespread understanding of the contrary as per previous international and regional studies. They also argue further the concept of specific association of hypovitaminosis D and autoimmune disease and certainly encourage wider estimation of 25(OH) D among larger numbers of patients in general medical practice. Finally, the outcomes of this work deserve further study/ies in larger groups in the future.

Association of hyperactivated transposon expression with exacerbated immune activation in systemic lupus erythematosus

BackgroundSystemic Lupus Erythematosus (SLE) is a complex autoimmune disorder, and transposable elements (TEs) have been hypothesized to play a significant role in its development. However, limited research has explored this connection. Our study aimed to examine the relationship between TE expression and SLE pathogenesis.MethodsWe analyzed whole blood RNA-seq datasets from 198 SLE patients and 84 healthy controls. The REdiscoverTE pipeline was employed to quantify TE and other gene expressions, identifying differentially expressed TEs. A TE score was calculated to measure overall TE expression for each sample. Gene ontology and gene set enrichment analyses were conducted to explore the functional implications of TE upregulation. Independent datasets were utilized to replicate the results and investigate cell type-specific TE expression.ResultsOur analysis identified two distinct patient groups: one with high TE expression and another with TE expression comparable to controls. Patients with high TE expression exhibited upregulation of pathways involving nucleic acid sensors, and TE expression was strongly correlated with interferon (IFN) signatures. Furthermore, these patients displayed deregulated cell composition, including increased neutrophils and decreased regulatory T cells. Neutrophils were suggested as the primary source of TE expression, contributing to IFN production.ConclusionsOur findings suggest that TE expression may serve as a crucial mediator in maintaining the activation of interferon pathways, acting as an endogenous source of nucleic acid stimulators in SLE patients.

The role of trimethoprim/sulfamethoxazole in preventing opportunistic infections in systemic lupus erythematosus patients receiving low-level immunosuppressive treatment: an open-label, randomized, controlled trial

Objective: Systemic lupus erythematosus (SLE) patients receiving immunosuppressive therapy are at risk for opportunistic infections (OIs), particularly Pneumocystis pneumonia (PCP). This study aimed to evaluate the effectiveness of trimethoprim/sulfamethoxazole (TMP/SMX) as primary prophylaxis against OIs and its adverse effects in SLE patients receiving low-level immunosuppressive treatment in a real-world setting. Methods: This open-label randomized controlled trial enrolled SLE patients receiving low-level immunosuppressive treatment at Ramathibodi Hospital between May 2021 and December 2022. Patient demographics and relevant clinical data were collected. Participants were randomized 1:1 to receive TMP/SMX or no prophylaxis, with dose adjustments according to renal function. The incidences of TMP/SMX-sensitive OIs and adverse events were monitored for 12 months post-enrollment. Results: The trial was terminated early due to a high rate of adverse drug reactions (ADRs) associated with TMP/SMX. In total, 138 SLE patients receiving low-level immunosuppressive treatment were enrolled. Most patients (98.4%) were in disease remission. No TMP/SMX-sensitive OIs were observed in either group during the 12-month follow-up period. Among individuals receiving TMP/SMX, 10/70 (14.3%) developed ADRs. Of these 10 patients, eight experienced grade 1 ADRs, and two had grade 3 ADRs; all declined to resume prophylaxis. There were no deaths in the study. Conclusions: During the 12-month follow-up period, no TMP/SMX-sensitive OIs occurred in SLE patients receiving low-level immunosuppressive therapy, suggesting that primary prophylaxis with TMP/SMX may not significantly benefit this population. The high rate of ADRs observed underscores the need for clinicians to carefully consider the risks and benefits of TMP/SMX prophylaxis in these patients.