Lupus Research Articles

Transition of patients with systemic lupus erythematosus from pediatric to adult-oriented rheumatology care

Transition of patients with systemic lupus erythematosus from pediatric to adult-oriented rheumatology care

Efficacy of combining aspirin with hydroxychloroquine in pregnancies at high risk for pre-eclampsia: a prospective, multicentre, open-label, single-arm clinical trial, investigator-initiated study (HUGS study)

IntroductionThe use of hydroxychloroquine (HCQ) during pregnancies complicated by systemic lupus erythematosus or refractory antiphospholipid antibody syndrome has demonstrated a significant ability to prevent pre-eclampsia (PE). As such, the potential...

Clinical presentation and management of vasculitis in an adolescent with Systemic Lupus Erythematosus: a case report

Systemic Lupus Erythematosus is a multifaceted autoimmune disease with diverse clinical manifestations, predominantly affecting females. This case report presents the clinical presentation and management of vasculitis in a 16-year-old male with SLE, an atypical demographic for the disease. The study examines the challenges of diagnosing and treating SLE in adolescents. The patient exhibited polyserositis, cutaneous vasculitis, malar rash, and oral ulcers. Diagnostic procedures included clinical evaluation, laboratory tests (ANA, anti-dsDNA, complement levels), and a skin biopsy histopathological examination. Treatment consisted of hydroxychloroquine, corticosteroids, and immunosuppressive agents. Laboratory findings revealed positive ANA, elevated anti-dsDNA titers, and low complement levels, confirming SLE with associated vasculitis. Histopathology verified skin-limited vasculitis. The patient responded well to the treatment regimen, achieving remission and reducing disease flares. Regular monitoring and a multidisciplinary approach were pivotal in managing the condition. This case underscores the importance of considering SLE in atypical demographics, such as adolescent males. Early diagnosis and comprehensive management are vital for improving outcomes and quality of life. Further research is warranted to address the unique challenges and optimal treatment strategies for pediatric and male SLE patients, emphasizing the need for awareness and tailored therapeutic approaches in managing chronic autoimmune diseases in diverse populations.

Primary ovarian insufficiency consequence of autoimmune diseases: a bidirectional two-sample Mendelian randomization study

BackgroundObservational studies suggest the risk of primary ovarian insufficiency (POI) is increased in autoimmune disorders (AIDs), but it is unclear whether there is a causal relationship. Therefore, we aimed to investigate the bidirectional causality between 20 AIDs and POI using Mendelian randomization (MR) analysis.MethodsA bidirectional two-sample MR investigation was designed by using publicly accessible summary-level data from genome-wide association studies (GWAS). The inverse variance weighted (IVW) method was performed as the main analysis, supplemented by several sensitivity analyses. Cochran Q test was used to evaluate SNP estimate heterogeneity. MR-Egger and MR-PRESSO methods were utilized to detect horizontal pleiotropy.ResultsThe MR analyses revealed that genetically determined coeliac disease (CeD) (OR = 1.124, 95% CI 1.033-1.224, P = 0.007), vitiligo (OR = 1.092, 95% CI 1.003-1.188; P = 0.042), systemic lupus erythematosus (SLE) (OR = 1.122, 95% CI 1.030-1.223, P = 0.008), and selective immunoglobulin A deficiency (SIgAD) (OR = 0.866, 95% CI: 0.776-0.967, P = 0.011) exhibited significant causal relationships with POI. We also found suggestive evidence of positive effect of Addison’s disease (AD) towards POI (OR5e-6 = 1.076, 95% CI 1.002-1.154, P = 0.043).ConclusionThis comprehensive MR analysis indicated that SLE, CeD, vitiligo, and AD caused an increased risk of POI, SIgAD was associated with a decreased risk of POI. These insights carry profound clinical implications, particularly emphasizing the early intervention for women with AIDs/POI who wish to preserve their reproductive potential or plan for future pregnancies.

Neurological involvement in patients with systemic autoimmune rheumatic diseases: a descriptive study in an Egyptian cohort

BackgroundNeurologic manifestations in the systemic autoimmune rheumatic diseases (SARDs) are protean. They add to the disease burden and could contribute to mortality. Increasing awareness about the neuro-rheumatologic syndromes might help with early diagnosis and effective therapy. Our aim is to survey the clinical and imaging patterns of neurological involvement in Egyptian patients with SARDs.ResultsNeurological involvement is common in Behçet’s disease (BD) (12.7%) and systemic lupus erythematosus (SLE) (6.4%) patients compared with other SARDs. Compared with SLE, neurological involvement in BD tends to develop at an older age (31 ± 7.1 versus 28.3 ± 9.6 years = 0.022) with a greater progression risk (13.8% versus 2.6%, P = 0.003). A higher proportion of SLE patients had abnormal neuroimaging without neurological symptoms (15.7% versus 4.3%, P = 0.026, OR = 4.9, 95%CI 1.1–22.4). SLE patients had a higher frequency of seizures (31.3% versus 6.4%, P < 0.001, OR = 6.7, 95%CI 2.7–16.7) and benign intracranial hypertension (9.6% versus 1.1%, P = 0.009, OR = 9.8, 95%CI 1.2–77.7) but a lower prevalence of quadriplegia due to brain insult (1.7% versus 3.2%, P = 0.045, OR = 0.2, 95%CI 0.04–0.9), dural sinus thrombosis (13% versus 33%, P = 0.001, OR = 0.3, 95%CI 0.2–0.6), brainstem syndrome (0.9% versus 6.4%, P = 0.047, OR = 0.1, 95%CI 0–1.1) and cranial neuropathies (9.6% versus 31.9%, P < 0.001, OR = 0.2, 95%CI 0.1–0.5). Concerning neuroimaging, brain atrophic changes were more common (27.4% versus 9.5%, P = 0.002, OR = 3.6, 95%CI 1.6–8.3) while thrombosis was less prevalent (36.3% versus 53.6%, P = 0.016, OR 0.5, 95%CI = 0.3–0.9) in lupus patients. The cerebral cortex was more commonly affected (20.4 versus 4.8%, P = 0.002, OR = 5.1, 95%CI 1.7–15.4) while dural sinuses (14.2% versus 40.5%, P < 0.001, OR = 0.2, 95%CI 0.1–0.5), basal ganglia (1.8% versus 10.7%, P = 0.010, OR = 0.2, 95%CI 0–0.7), diencephalon (0% versus 13.1%, P < 0.001) and brainstem (1.8% versus 22.6%, P < 0.001, OR = 0.1, 95%CI 0–0.3) were less frequently involved in SLE patients. Concerning other SARDs, cranial neuropathies were the most common neurological presentations. Abnormalities in neuroimaging did not correlate with the patients’ clinical presentations.ConclusionsNeurological presentations associated with SARDs are protean. Neuroimaging abnormalities should be interpreted within the context of the clinical picture and the results of other investigations.

An Unusual Case of Overlapping Immunoglobulin G4-Related Disease and Systemic Lupus Erythematosus

An Unusual Case of Overlapping Immunoglobulin G4-Related Disease and Systemic Lupus Erythematosus

Gonococcal arthritis with systemic involvement: A case report

Abstract: INTRODUCTION Septic arthritis caused by N. gonorrhoeae is rare in our setting. Systemic dissemination may present as a characteristic triad of skin rash, tenosynovitis and arthritis. CASE PRESENTATION A 47-year-old man, previously healthy, had oligoarticular pain for seven days. He developed polyarthralgia and skin lesions. Arthrocentesis, blood cultures and laboratory tests with a rheumatological profile were performed. Antibiotic treatment was started and subsequent arthroscopic debridement of the knee was performed after synovial fluid and laboratory analysis. Blood cultures revealed N. gonorrhoeae . The patient complied with antibiotic treatment and evolved favorably until he recovered completely. DISCUSSION N. Gonorrhoeae has a low systemic dissemination. Joint involvement may resolve spontaneously. Tenosynovitis affects more the dorsum of the hands and wrists. The skin lesions are purplish macules that may develop into vesicles or pustules. There may be immunological lesions. Cultures are often negative. Other pathologies with joint and skin involvement should be known, such as systemic lupus erythematosus, psoriatic arthritis and reactive arthritis. Treatment consists of surgical debridement and antibiotics. In contrast to other septic arthritis, complications are rare and the prognosis is good.

25 Years of Biologics For The Treatment of Pediatric Rheumatic Diseases - Advances in Prognosis and Ongoing Challenges.

There are over 100 rheumatic diseases and approximately 300,000 children with a pediatric rheumatic disease (PRD) in the United States (U.S.). The most common PRDs are juvenile idiopathic arthritis (JIA), childhood-onset systemic lupus erythematosus (cSLE), and juvenile dermatomyositis (JDM). Effective and safe medications are essential because there are generally no cures for these conditions. Etanercept was the first biologic therapy for the treatment of JIA, approved in 1999. Since then, other biologic disease modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARD (tsDMARDs) blocking relevant immunological pathways have been approved for the treatment of JIA, resulting in a marked improvement of disease prognosis. Conversely, there is only one bDMARD that has been approved for cSLE, but none are approved for the treatment of JDM. Lack of approved therapeutic options, with established dosing regimens and known efficacy and safety, remains a central challenge in the treatment of all PRDs, including autoinflammatory diseases, and for complications of PRDs. This review provides an overview of bDMARD and tsDMARD treatments studied for the treatment of various subtypes of JIA, summarizes information from bDMARD studies in other pediatric rheumatic diseases, with a focus on pivotal trials that led to regulatory approvals and highlights improved outcomes in JIA with the use of these newer medications. Further, we outline barriers and challenges in the treatment of other PRDs. Lastly, we summarize the current regulatory landscape for bDMARD studies and medication approvals in PRDs.

Comprehensive analysis of IRF8-related genes and immune characteristics in lupus nephritis

BackgroundThere are currently no reliable diagnostic biomarkers or treatments for lupus nephritis (LN), a complication of systemic lupus erythematosus. Objective: We aimed to explore gene networks and potential biomarkers for LN by analyzing the GSE32591 and GSE113342 datasets from the Gene Expression Omnibus database, focusing on IRF8 and IRF8-related genes.MethodsWe used differential expression analysis, functional enrichment, protein-protein interaction (PPI) network construction, and the CIBERSORT algorithm for immune infiltration assessment. To validate the expression levels of the IRF8 gene in the kidneys of lupus mice models, we used quantitative real-time PCR (qRT-PCR) and Western blotting (WB). A diagnostic classifier was built using the RandomForest method to evaluate the diagnostic potential of selected key genes. To bridge our findings with potential therapeutic implications, we used the drug-gene interaction database to predict drugs targeting the identified genes.ResultsTwenty co-differentially expressed genes (DEGs) were identified, with IRF8 exhibiting significant expression differences and potential as a biomarker. Functional enrichment analysis revealed pathways associated with immune response. Validation through qRT-PCR and WB confirmed that the IRF8 gene and its protein exhibited elevated expression levels in the kidneys of lupus mice compared to control groups. The diagnostic classifier revealed impressive accuracy in differentiating LN from control samples, achieving a notable area under the curve values across various datasets. Additionally, immune infiltration analysis indicated significant differences in the immune cell profiles between the LN and control groups.ConclusionIRF8 and its related genes show promise as biomarkers and therapeutic targets for LN. These findings contribute to a deeper understanding of the molecular mechanisms involved in LN and may support the development of precision medicine strategies for improved patient outcomes.

Serum 25-Hydroxyvitamin D Levels and Disease Activity in Patients with Systemic Lupus Erythematosus: An Exploratory Study in Western Mexico

Background and objectives: The correlation between diminished 25-hydroxyvitamin D (25-(OH)D) concentrations and heightened disease activity in systemic lupus erythematosus (SLE) patients remains contentious, as clinical studies have yielded conflicting outcomes—some propose a potential link, while others assert no relationship exists. Nonetheless, all studies report a significant prevalence of low 25-(OH)D levels among SLE patients. This study aimed to assess the frequency of low serum levels of 25-(OH)D in Mexican patients with SLE and to evaluate the correlation between 25-(OH)D deficiency or insufficiency and disease activity levels. Materials and Methods: This retrospective analysis comprised patients admitted to our hospital from November 2022 to October 2023, diagnosed with SLE, and had their serum 25-(OH)D levels tested upon admission. The frequency of low levels of 25-(OH)D was assessed, and clinical and demographic data were gathered to examine potential causes linked to 25-(OH)D deficiency or insufficiency. Results: A total of 61 patients were included, and 87% (n = 53) had low serum 25-(OH)D levels. Patients with 25-(OH)D deficiency (n = 21) were significantly younger (mean 23 vs. 39 years, p = 0.04) and had higher protein levels in 24 h urine protein (1.8 vs. 1.1 g/24 h, p = 0.006) than patients who presented only 25-(OH)D insufficiency, without significant differences in other indicators of disease activity. Conclusions: In this investigation, patients with SLE exhibited a high frequency of low serum levels of 25-(OH)D, consistent with existing literature; however, no significant correlations were identified between 25-(OH)D levels and indicators of disease activity. These findings require validation in subsequent research.

Transient Anti-TCRβ mAb Treatment Induces CD4+ T Cell Exhaustion and Prolongs Survival in a Mouse Model of Systemic Lupus Erythematosus.

T cells play a critical role in the pathogenesis of systemic lupus erythematosus (SLE). Chronic T cell receptor (TCR) signalling induces T cell exhaustion, characterised by reduced capacity to induce tissue damage. Here, we investigated the therapeutic potential of the anti-TCRβ (H57-597) monoclonal antibody (mAb) in a mouse model of SLE. Four-month-old MRL/lpr mice exhibiting SLE phenotypes received 5 weekly doses of anti-TCRβ mAb or phosphate-buffered saline (PBS) vehicle control. Subsequently, mouse survival was monitored daily. On day 1 post the final dose of treatment, SLE pathogenesis was determined using histological staining and spot urine test. T and B cell states in the brain, kidney, and secondary lymphoid organs were determined by flow cytometry. Transient treatment of anti-TCRβ mAb significantly prolonged the survival of MRL/lpr mice. Accordingly, MRL/lpr mice in the anti-TCRβ mAb group exhibited decreased proteinuria scores and minimal renal pathological damage compared to the PBS control group. Flow cytometric analysis revealed that anti-TCRβ mAb treatment resulted in a reduction in the frequencies of CD4+ T cells and CD138+B220lo/- plasma cells, plus an increase in Foxp3+ regulatory T cell frequency. Furthermore, CD4+ T cells from anti-TCRβ mAb treated mice exhibited elevated expression levels of PD-1 and TIM-3, with reduced IFN-γ production, indicative of an exhaustion-like phenotype. Therefore, transient administration of anti-TCRβ mAb treatment induces an exhaustion-like phenotype in CD4+ T cells, resulting in prolonged survival of MRL/lpr mice. Inducing autoreactive T-cell exhaustion holds promise as an attractive therapeutic approach for SLE.

Measuring Frailty in Systemic Lupus Erythematosus.

Recent research has explored frailty in systemic lupus erythematosus (SLE) using multiple measures. We examined the agreement among frailty measures and the association of each with cross-sectional and longitudinal health outcomes. We used data from the California Lupus Epidemiology Study (CLUES) to examine the following measures of frailty: Systemic Lupus International Collaborating Clinics (SLICC) Frailty Index (SLICC-FI), Short Physical Performance Battery (SPPB), and Fatigue, Resistance, Ambulation, Illness, and Loss of Weight (FRAIL) scale questionnaire. PROMIS Physical Function 10a (PF) was tested as a proxy measure of frailty. Agreement between frailty classifications by each measure was assessed. Cross-sectional associations of frailty classifications with hospitalization, valued life activities disability, cognitive impairment, 6-minute walk test distance, self-reported disease damage, fatigue, and depressive symptoms were assessed with logistic and linear regression analyses. Associations with hospitalization, disease damage increase, and disability increase over the subsequent 3 years were assessed Cox proportional hazards analyses. Percentages of participants identified as frail varied among the measures, from 10.8% to 45.9%. Agreement among classifications ranged from slight to substantial (κ from 0.17 to 0.63). Most of the frailty measures were associated with both cross-sectional and longitudinal health outcomes, with the notable exception of the SPPB. SLICC-FI had the most consistent association with outcomes, followed by FRAIL and PF. Multiple measures of frailty appear to identify the risk of poor health outcomes. The intended use, as well as the simplicity and practicality of implementing the measure, may be the most important considerations in choosing a frailty measure.

Topical mupirocin treatment reduces interferon and myeloid signatures in cutaneous lupus erythematous lesions through targeting of Staphylococcus species.

Cutaneous lupus erythematosus (CLE) is an inflammatory skin manifestation of systemic lupus erythematosus (SLE). Type I interferons (IFNs) promote inflammatory responses and are elevated in CLE lesions. We recently reported that CLE lesions are frequently colonized with Staphylococcus aureus (S. aureus). Here, we follow up in a proof-of-concept study to investigate whether type I IFN and inflammatory gene signatures in CLE lesions can be modulated with mupirocin, a topical antibiotic treatment against S. aureus-mediated skin infections. Participants with active CLE lesions (n=12) were recruited and randomized into a week of topical treatment with either 2% mupirocin or petroleum jelly vehicle. Paired samples were collected before and after 7 days of treatment to assess microbial lesional skin responses. Microbial samples from nares and lesional skin were used to determine baseline and post-treatment Staphylococcus abundance and microbial community profiles by 16S rRNA gene sequencing. Inflammatory responses were evaluated by bulk RNA sequencing of lesional skin biopsies. We identified 173 differentially expressed genes in CLE lesions after topical mupirocin treatment. Decreased lesional Staphylococcus burden correlated with decreased IFN pathway signaling and inflammatory gene expression and barrier dysfunction. Interestingly, mupirocin treatment lowered skin monocyte levels, and this mupirocin-associated depletion of monocytes correlated with decreased inflammatory gene expression. Mupirocin treatment decreased lesional Staphylococcus, and this correlated with decreased IFN signaling and inflammatory gene expression. This study suggests a topical antibiotic could be employed to decrease lupus skin inflammation and type I IFN responses by reducing Staphylococcus colonization.

Practical Approach of Trayopstambha in Preventing Autoimmune Disorders

Trayopstambha are – Aahar, Nidra and Brahmcharya. All of them are helpful for living a healthy life. In all autoimmune disease like Rheumatoid Arthritis, Lupus Erythematous, Celiac diseases, Polymyalgia, Multiple Sclerosis, Type 1 DM and Alopecia aerata body immune system is affected due to over activity of free radicals. Free radicals’ activity is increased due to disbalance in Trayopstambha. Aama Rasa is responsible for development of all autoimmune diseases. This Aama Rasa can be compared to free radical which causes destruction of healthy tissues. Aama's etiological factors may be classified as Aharja, Viharaja and Manasika. Not only food in larger amount, but also qualities such as Guru, Sheeta, Shushka, Ruksha, Vidahi, Viruddha Ahara (incompatible diet), Ajeernabhojana (indigestion), Asatmya Bhojana (toxic food) or Abhojana (self-restraint from food), Deevasvapna (keeping wakeful in the night and sleeping in the day), are chief factors accountable for the creation of Aama. The condition of Aama formation is also exaggerated by mental disorder due to disturbance in Nidra and Brahmcharya. Acharya Sushruta stressed that Nidana is the simple and uttermost basis for a treatment. Prevention is always better than a cure. If we follow proper regimen of Trayopstambha it makes metabolism better, decrease free radical activity in body and reduce the risk of autoimmune diseases.

Bullous Erythema Multiforme or Rowell Syndrome: A Case Report

Bullous erythema multiforme is characterized by the presence of target lesions with a bullous center, distributed bilaterally and relatively symmetrically on the extremities. Rowell's syndrome is a type of subacute cutaneous lupus erythematous that mimics erythema multiforme. These two diagnoses have a similar histopathology with interface dermatitis. To differentiate these two entities, we use the criteria of Rowell et al., Lee et al., Zeitouni et al., or Torchia et al., According to these criteria, the diagnosis of Rowell syndrome requires the presence of lupus lesions and antinuclear antibodies. In our case, the pathologist mistook erythema multiforme for subacute cutaneous lupus because of the presence of interface dermatitis. However, our patient did not meet any of the criteria for the diagnosis of Rowell's syndrome. The patient was treated as having erythema multiforme with a good outcome.

A systematic review of the efficacy of TYK2 inhibitors in patients with dermatological disease.

This study systematically reviews existing data on the efficacy of Tyrosine Kinase 2 (TYK2) inhibitors in comparison to placebo or standard treatments for therapeutic benefit and improving quality of life in dermatological diseases. Seventeen records representing 13 clinical trials, one matching-adjusted indirect comparison, and one case study were included. Results indicate that Deucravacitinib is superior to placebo, Apremilast and Adalimumab in treating adult patients with moderate-to-severe plaque psoriasis and superior to placebo in the treatment of adults with systemic lupus erythematosus. Comparative investigations on Brepocitinib and Ropsacitinib were more limited. Oral Brepocitinib demonstrated superiority over placebo in managing alopecia areata, and hidradenitis suppurativa. Topical Brepocitinib exhibited superiority over placebo in treating atopic dermatitis, but not plaque psoriasis. Ropsacitinib demonstrated superiority over placebo in the management of plaque psoriasis. Brepocitinib and Ropsacitinib had more side effects than Deucravacitinib.

Estimation of TNF- α and some immunological parameters in patient with systemic lupus erythematosus

Abstract: Abstract— Systemic Lupus Erythematosus (SLE) is a multifactorial chronic systemic autoimmune disease. It is characterized by a lack of immune tolerance to autoantigens such as nuclear antigens. In this study, 25 individuals diagnosed with SLE had their blood samples drawn, while 25 healthy individuals were used as a control group. The results of this investigation show that the patients' TNF-α levels (106.9 ± 10.8) significantly increased more than 52.86 in the control group. Comparing the immunological parameters of the patients to the healthy group, the study revealed a decrease in the eosinophile, basophile, lymphocyte, and monocyte counts (010 ± 0.003, 0.022 ± 0.004, 1.71 ± 0.66, 0.21 ± 0.047 respectively) and a rise in the neutrophile and immature granulocyte counts (7.43 ± 1.66, 2.68 ± 0.46 respectively) in SLE patient. Keywords— SLE,TNF‑α,immunological parameters

Evaluation of the Immunological and Hematological parameters of Systemic Lupus Erythematosus in Iraqi Women

Systemic lupus erythematosus is an autoimmune disease involving several systems, mainly affects young adult women, and causes a significant deterioration in quality of life. Different environmental aspects are known to facilitate the development of lupus in predisposed individuals. Hemoglobin concentration (HB), granulocyte level, hemoglobin level, saturation (ESR), and platelets (PLT) were among the clinical blood indicators that were found to be associated with the beginning of SLE in adults and teenagers. Blood PLT levels in both SLE patients were significantly lower than in the G1 control group (P&lt; 0.001). When compared to the control group, G1, the two SLE patient groups (G2 &amp; G3) had noticeably higher ESRs (P &lt; 0.01). The study employed many immunological markers, such as C-reactive protein (CRP), antinuclear antibody (ANA), Anti-double stranded DNA (Anti-dsDNA), complement components C3 and C4 levels. Serum CRP levels were significantly higher in G2 and G3 SLE patients (P&lt;0.001) than in the G1 control group. Research revealed that two SLE patient groups (G2 &amp; G3) had blood levels of ANA and Anti-double stranded DNA (Anti-dsDNA) that were considerably higher than those of the control group (G1).

Changes in Quality of Life Domains among Saudi Patients with Systemic Lupus Erythematosus before and during the COVID-19 Pandemic

Changes in Quality of Life Domains among Saudi Patients with Systemic Lupus Erythematosus before and during the COVID-19 Pandemic

Pharmacokinetics, Pharmacodynamics, Bioavailability, and Immunogenicity of Obexelimab Following Subcutaneous Administration in Healthy Japanese and Non-Japanese Volunteers.

Obexelimab is an investigational, bifunctional, non-depleting, humanized monoclonal antibody that binds CD19 and FcγRIIb to inhibit B cells, plasmablasts, and CD19-expressing plasma cells. In clinical trials, intravenous (IV) administration of obexelimab has been well-tolerated, and demonstrated clinical activity in patients with rheumatoid arthritis, systemic lupus erythematosus, and immunoglobulin G4-related disease. This study was performed to evaluate the pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of obexelimab following subcutaneous (SC) administration, and compare PK/PD profiles between healthy Japanese and non-Japanese volunteers. This was a Phase I, open-label, parallel group, multiple-dose study. Participants were randomized to five cohorts to receive three doses of obexelimab as 125mg SC every 14days (q14d), 250mg SC q14d, 375mg SC q14d, 250mg IV q14d, and 125mg SC every 7days, then monitored during a 28-day safety follow-up period. PK/PD assessments were performed after the first and third doses. A total of 50 healthy volunteers (25 Japanese and 25 non-Japanese) were enrolled and distributed evenly between dose cohorts. All SC dosing regimens were well-tolerated. Dose-proportional PK was observed following SC doses with a bioavailability of approximately 60%. No clinically meaningful differences in PK parameters were found between healthy Japanese and non-Japanese participants. Antidrug antibodies (ADA) were detected in 6/50 (12%) participants after dosing. ADA had no or minimal impact on PK in all six ADA positive participants. Near-complete CD19 receptor occupancy and an absolute B-cell count nadir of approximately 50% baseline levels were maintained for the duration of the study in both populations. Obexelimab SC administration demonstrated favorable bioavailability, was well-tolerated, and showed no clinically meaningful ethnic differences in PK/PD. These results support further clinical development of SC obexelimab to treat B-cell mediated autoimmune diseases. NCT02867098.