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Systemic lupus erythematosus (SLE) is a complicated multisystem autoimmune disease that carries substantial mortality and morbidity. The development of new therapies is partly hindered by the lack of a flawless instrument to gauge disease activity in different organs for the primary efficacy outcome. Until a global consensus is reached regarding the most preferred assessment tool, application of any of the existing disease activity indices is acceptable in clinical practice and research. However, one should have a more thorough understanding of the strength and limitations of individual disease activity instruments. This article updates the SLE disease activity indices commonly used in clinical trials and their latest stage of development.

Coronavirus disease 2019 (COVID-19) was one of the most important infections in the past few years. Although most cases of COVID-19 are mild, serious complications may arise. The multisystem inflammatory syndrome (MIS) is a rare but severe, yet poorly understood complication of COVID-19. It was first described in childhood patients with COVID-19 (MIS-C) but is increasingly reported in adults. MIS-A may lead to diagnostic and therapeutic dilemma as its manifestations may mimic a flare of the underlying disease and the use of immunosuppressive therapy may further increase the risk of other infective complications in these patients. However, MIS-A has rarely been reported in patients with pre-existing autoimmune conditions. We hereby present a patient with systemic lupus erythematosus who developed severe MIS-A 6 weeks after a recent SARS-CoV-2 infection.

Objective: To study the predictive value of a positive anti-nuclear antibody (ANA) for a rheumatological diagnosis in an outpatient setting. Methods: Individuals who were referred to the rheumatology outpatient clinics because of a positive ANA between July 2014 and June 2015 were retrospectively reviewed. Presenting symptoms in addition to a positive ANA and whether a final rheumatological diagnosis was made were recorded. The positive predictive value of a positive ANA and its titer for a rheumatological diagnosis, with and without accompanying symptoms was evaluated. Results: A total of 230 patients were included (82% women, age 47.7 ± 14.1 years [range 18-84]). Family medicine and the general outpatient clinic were the main sources of referral (32.2%), followed by ophthalmology (13.0%) and otorhinolaryngology (11.7%). A final rheumatological diagnosis was made in 54 (23.5%) patients, with rheumatoid arthritis being the commonest diagnosis (40.7%). In the absence of any associated symptoms, the predictive value of a positive ANA was 0%. The presence of Raynaud’s phenomenon (100%), joint swelling (59.5%), and joint stiffness (48.9%) predicted a better final rheumatological diagnosis along with a positive ANA. ANA titers of 1:80 or less had a low sensitivity for rheumatic diseases. A receiver operating characteristic (ROC) curve analysis showed that an ANA titer of [Formula: see text]1:128 best predicted a rheumatological diagnosis (AUC 0.78 [0.71–0.85]; sensitivity 0.78; specificity 0.64). Conclusions: To improve the prediction for a rheumatological diagnosis, referral for a positive ANA test should be more appropriately done with compatible symptoms.

Objective: To evaluate the performance of the Hospital Anxiety and Depression Scale (HADS) for screening of depressive disorders and anxiety disorders in patients with rheumatoid arthritis (RA) in Hong Kong. Methods: Consecutive RA patients in the outpatient clinic of Pok Oi Hospital were invited to complete the validated Chinese-Cantonese version of the HADS questionnaire before clinical assessment by a psychiatrist for depressive disorders and anxiety disorders using the Chinese-bilingual Structured Clinical Interview for DSM-IV Axis I disorders, patient research version. Psychometric properties of the HADS were analyzed by the receiver operating characteristic (ROC) curve analysis. Results: For the HADS full scale, sensitivity and specificity at the optimal cut-off score of 16 for any psychiatric disorders were 83.0% and 81.0%, respectively (area under ROC curve [AUC] 0.91). For the depression subscale (HADS-D), sensitivity and specificity at the optimal cut-off score of 10 for any depressive disorders were 89.7% and 84.8%, respectively (AUC 0.93). For the anxiety subscale (HADS-A), sensitivity and specificity at the optimal cut-off score of 8 for any anxiety disorders were 88.5% and 74.1%, respectively (AUC 0.87). The HADS-D showed better screening properties for any depressive disorders than major depressive disorder. The HADS-A showed better screening properties for generalized anxiety disorder than any anxiety disorders. Conclusion: The HADS had good performance to screen for any psychiatric disorders and the HADS-D had good performance to screen for any depressive disorders. On the other hand, the HADS-A performed better for generalized anxiety disorder than for any anxiety disorders.

ObjectivesLupus nephritis (LN) remains one of the most severe manifestations in patients with systemic lupus erythematosus (SLE). Onset and overall LN risk among SLE patients remains considerably difficult to predict. Utilizing a territory-wide longitudinal cohort of over 10 years serial follow-up data, we developed and validated a risk stratification strategy to predict LN risk among Chinese SLE patients – Risk and Factors associated with disease manifestations in systemic Lupus Erythematosus – Lupus Nephritis (RIFLE-LN).MethodsDemographic and longitudinal data including autoantibody profiles, clinical manifestations, major organ involvement, LN biopsy results and outcomes were documented. Association analysis was performed to identify factors associated with LN. Regression modelling was used to develop a prediction model for 10-year risk of LN and thereafter validated.ResultsA total of 1652 patients were recruited: 1382 patients were assigned for training and validation of the RIFLE-LN model; while 270 were assigned for testing. The median follow-up duration was 21 years. In the training and validation cohort, 845 (61%) of SLE patients developed LN. Cox regression and log rank test showed significant positive association between male sex, age of SLE onset and anti-dsDNA positivity. These factors were thereafter used to develop RIFLE-LN. The algorithm was tested in 270 independent patients and showed good performance (AUC = 0·70).ConclusionBy using male sex, anti-dsDNA positivity, age of SLE onset and SLE duration; RIFLE-LN can predict LN among Chinese SLE patients with good performance. We advocate its potential utility in guiding clinical management and disease monitoring. Further validation studies in independent cohorts are required.

The risk of osteoporosis and fragility fracture is increased in patients with autoimmune rheumatic diseases. Although the use of glucocorticoids is the major contributing factor, inflammation mediated by cytokines and growth factors and other medications, including the biologic and targeted disease-modifying antirheumatic drugs, also play important roles in bone remodeling. Pro-inflammatory cytokines such as IL-1, IL-6, IL-17, and TNF[Formula: see text] increase RANK expression and promote osteoclast activity while inhibiting osteoblast-mediated bone formation through the Dickkopf-1 pathway. Certain autoantibodies stimulate differentiation of the osteoclasts, resulting in localized bone resorption. This article covers the prevalence and risk factors for osteoporosis in patients with common rheumatic diseases and the role of inflammatory cytokines and other clinical factors. Controlling disease-related inflammation and optimizing the diagnostic and therapeutic instrumentation is needed to reduce fragility fractures in patients with rheumatic diseases.

Background: Systemic lupus erythematosus (SLE) is a multisystem autoimmune disorder mainly affecting women of childbearing age. Mortality and organ damage of SLE is mainly due to uncontrolled disease activity and treatment-related toxicities. Thus, assessment of disease activity is important during routine clinical practice. In recent years, neutrophil-to-lymphocyte ratio (NLR) has been explored as a marker of disease in many autoimmune disorders including SLE. As such, our study objective is to investigate the correlation between neutrophil-to-lymphocyte ratio (NLR) and disease activity of SLE using the SLE disease activity score (SLE-DAS) in our local population. Methods: Consecutive adult patients who fulfilled the ACR or SLICC criteria for SLE were recruited between March 2023 and February 2024. SLE activity was assessed by SLE-DAS, physicians’ global assessment (PGA) and SLE disease activity index-2000 (SLEDAI-2K). The calculated NLR was correlated with disease activity indices and serological parameters (anti-dsDNA, C3/4) by Spearman’s rank correlation. Patients were stratified into remission, low and moderate/severe disease activity as defined by the SLE-DAS and comparison of the NLR was performed among these subgroups by one-way ANOVA. Results: A total of 420 SLE patients were studied (96.2% women, age 46.0± 11.0 years, SLE duration 16.4± 8.3 years). Moderate/severe, low disease activity and SLE-DAS remission was present in 70(16.7%), 66(15.7%), and 284(67.6%) patients, respectively. SLE-DAS correlated significantly with SLEDAI-2K (rho 0.9; p0.5, active sediments or histological features) than inactive SLE (4.62 vs 3.27; p=0.02). The NLR in patients with moderate/severe SLE-DAS activity was significantly higher than those in remission (4.87 vs 3.27; p=0.007). ROC analysis showed that a NLR cut-off of 3.11 showed a sensitivity of 55.6% and specificity of 68.7% in detecting moderate/severe SLE-DAS (AUC 0.67[0.6-0.7]; p

The ultimate goal of treatment of systemic lupus erythematosus (SLE) is to prolong survival without compromising the quality of life. The survival rates of SLE have plateaued since the 2000s’ and morbidities related to disease activity and treatment are still problematic. A big unmet need for SLE therapy is to develop strategies that can enhance efficacy, reduce disease flares and drug related complications. Cocktail immunosuppressive therapies for the synergistic effect of individual drugs may enhance efficacy and enable dosage reduction. However, risk of infective complications, adoption of a step-up or step-down approach and the choice of agents are still controversial, partly because of the issue of cost-effectiveness. Belimumab is the first biological agent licensed for pediatric and adult patients with renal and non-renal SLE, based on several pivotal randomized controlled trials (BLISS-52, BLISS-76, BLISS-NEA, BLISS-SC, BLISS-LN). The continuous use of belimumab enables reduction of disease flares, glucocorticoid doses and organ damage. Anifrolumab, a monoclonal antibody against type I interferon receptors, has shown efficacy for non-renal SLE in the TULIP studies. It is recently licensed for moderate to severe SLE patients who are receiving standard therapies. Although rituximab did not show benefit in renal and non-renal SLE, it is commonly used off-label to treat refractory lupus manifestations. The newer generation anti-CD20 biologic, obinutuzumab, shows promising preliminary results in a phase 2 lupus nephritis (LN) trial. Combination of anti-CD20 and anti-BAFF is being studied in LN but the results are conflicting hitherto. Ianalumab, a monoclonal antibody against BAFF receptor that exhibits dual mechanisms of action (BAFF inhibition and B cell depletion), is being studied in LN. The updated 2023 EULAR recommendations for SLE have included the role of biological agents in the treatment algorithm. Belimumab and anifrolumab may be considered in non-major organ SLE, including skin disease, that is refractory to hydroxychloroquine with or without other immunosuppressive agents. Initial combination therapy of glucocorticoids, mycophenolate mofetil or low dose cyclophosphamide, with belimumab is an option for the treatment of severe LN, and belimumab may be used as long-term maintenance therapy of SLE/LN. In this talk, the evidence and the role of the older and newer biologic and targeted agents in SLE/LN will be reviewed.

Patients with immune-mediated inflammatory diseases on anti-tumor necrosis factor (TNF) agents are at increased risk of developing active tuberculosis (TB). Screening and treatment of latent tuberculosis infection (LTBI) with the use of a standard screening protocol is important in reducing the risk of TB reactivation during therapies with anti-TNF agents. The Latent Tuberculosis Infection Working Group under the Tuberculosis Control Coordinating Committee of the Department of Health and the Hospital Authority has reviewed and assessed local and international scientific evidence and formulated guideline statements on the management of LTBI in patients initiating anti-TNF biologics.

Endometriosis is an estrogen-dependent gynecological disease with chronic pelvic inflammation. In order to study the pathophysiology of endometriosis and examine the therapeutic effects of new pharmaceuticals for endometriosis treatment, different animal models had been developed in the last two decades, especially mouse models. However, no study evaluated the effects of various modeling approaches on pathology and immunology in endometriosis. This study aimed to compare endometriotic lesion development and immune profiles under different methods of establishing endometriosis models in mice, including estrus synchronization (ovariectomy with estrogen supplement versus male urine-soaked transfer bedding), endometrium preparations (whole uterus including endometrium and myometrium fragments versus solely endometrium fragments), and surgical transplantation (subcutaneous transplantation versus intraperitoneal injection). Our results showed that lesion growth under estrus synchronization by ovariectomy with estrogen supplement had a higher success rate and more proliferative endometrium, apart from higher body weight gain. Immune responses in peripheral blood were similar in the whole uterus and solely endometrium fragments and in intraperitoneal injection and subcutaneous transplantation, but a more innate immune response in the peritoneal microenvironment was found in solely endometrium fragments and intraperitoneal injection than counterparts. In conclusion, different endometriosis modeling methods result in different pathological and immunological features. Ovariectomy with estrogen supplement, solely endometrium fragments, and intraperitoneal injection are more suitable for both pathological and immunological studies of endometriosis in mice, which are important for mechanistic studies and immunotherapy development.

ObjectivesThe goal of this exploratory study is to determine if urine:serum fractional excretion ratios can outperform the corresponding urinary biomarker proteins in identifying active renal disease in systemic lupus erythematosus (SLE).MethodsThirty-six adult SLE patients and twelve healthy controls were examined for serum and urine levels of 8 protein markers, namely ALCAM, calpastatin, hemopexin, peroxiredoxin 6 (PRDX6), platelet factor 4 (PF4), properdin, TFPI and VCAM-1, by ELISA. Fractional excretion of analyzed biomarkers was calculated after normalizing both the urine and serum biomarker levels against creatinine. A further validation cohort of fifty SLE patients was included to validate the initial findings.ResultsThe FE ratios of all 8 proteins interrogated outperformed conventional disease activity markers such as anti-dsDNA, C3 and C4 in identifying renal disease activity. All but VCAM-1FE were superior to the corresponding urine biomarkers levels in differentiating LN activity, exhibiting positive correlation with renal SLEDAI. ALCAMFE, PF4FE and properdinFE ratios exhibited the highest accuracy (AUC>0.9) in distinguishing active LN from inactive SLE. Four of the FE ratios exhibited perfect sensitivity (calpastatin, PRDX6, PF4 and properdin), while ALCAMFE, PF4FE and properdinFE exhibited the highest specificity values for active LN. In addition, several of these novel biomarkers were associated with higher renal pathology activity indices. In the validation cohort ALCAMFE, PF4FE and properdinFE once again exhibited higher accuracy metrics, surpassing corresponding urine and serum biomarkers levels, with ALCAMFE exhibiting 95% accuracy in distinguishing active LN from inactive SLE.ConclusionsWith most of the tested proteins, urine:serum fractional excretion ratios outperformed corresponding urine and serum protein measurements in identifying active renal involvement in SLE. Hence, this novel class of biomarkers in SLE ought to be systemically evaluated in larger independent cohorts for their diagnostic utility in LN assessment.

Patients with autoimmune rheumatic diseases are potentially at risk of more serious Coronavirus Disease 2019 (COVID-19) infection and increased mortality due to immunosuppressive therapies and disease-related medical comorbidities. Uncertainty about the safety and efficacy of the COVID-19 vaccines is a major deterrent for patients to participate in the vaccination program. The Hong Kong Society of Rheumatology took the lead to publish a set of consensus statements for COVID-19 vaccination in adult patients with autoimmune rheumatic diseases through a Delphi exercise that involved the senior members of the Society. This serves as a guide to rheumatologists and other specialists, nurses, healthcare professionals, and public regarding COVID-19 vaccination in autoimmune rheumatic diseases.

Although glucocorticoids (GCs) are the cornerstone for the treatment for systemic lupus erythematosus (SLE), they are associated with a number of adverse effects. Recently, an open randomized controlled trial (RCT) conducted in France showed that flares of SLE in 12 months were significantly more common with GCs withdrawal than continuation in stable patients. However, the study did not separately report results on subsets of SLE patients with organ threatening disease such as lupus nephritis (LN). We hereby present a literature review on GCs withdrawal in SLE and propose a protocol for a multicenter RCT in Hong Kong to evaluate the feasibility of withdrawal of low-dose GCs in stable LN patients who are in clinical remission.

Systemic lupus erythematosus (SLE) is an autoimmune disease with involvement of multiple systems. Despite the therapeutic advances in the past few decades, refractory SLE causing organ damage and life-threatening complications still poses a therapeutic challenge. Therapeutic plasma exchange is considered as one of the rescue therapies used in refractory SLE. However, the level of evidence supporting its use is low. This article reviews the current evidence of the application of plasmapheresis in the treatment of SLE.

Glucocorticoid (GC)-induced osteoporosis (GIOP) is a major problem in patients with rheumatic diseases. The deleterious effect of GC on bone turnover is rapid and dose-dependent, with a predilection on the trabecular bone, resulting in vertebral fractures. Early recognition and prompt treatment of GIOP helps prevent bone loss and reduce fractures. There are pitfalls in current assessment tools for GIOP by dual-energy X-ray absorptiometry (DXA) and fracture risk assessment tool (FRAX) estimation formula. In this review, we evaluate different assessment methods for GIOP and summarize current therapies of GIOP, including the antiresorptive and anabolic agents. The potential role of newer anti-osteoporosis agent romosozumab, an anti-sclerostin monoclonal antibody, is also discussed.

On March 12, 2020, the World Health Organization (WHO) declared coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) a pandemic. The rapidly increasing number of cases and deaths have overwhelmed the health care system worldwide. We aimed to provide a narrative review on some practical issues of COVID-19 and rheumatic diseases with the limited data to the date of April 26, 2020.

Human complement C4 is one of the most diverse but heritable effectors for humoral immunity. To help understand the roles of C4 in the defense and pathogenesis of autoimmune and inflammatory diseases, we determined the bases of polymorphisms including the frequent genetic deficiency of C4A and/or C4B isotypes. We demonstrated the diversities of C4A and C4B proteins and their gene copy number variations (CNVs) in healthy subjects and patients with autoimmune disease, such as type 1 diabetes, systemic lupus erythematosus (SLE) and encephalitis. We identified subjects with (a) the fastest migrating C4B allotype, B7, or (b) a deficiency of C4B protein caused by genetic mutation in addition to gene copy-number variation. Those variants and mutants were characterized, sequenced and specific techniques for detection developed. Novel findings were made in four case series. First, the amino acid sequence determinant for C4B7 was likely the R729Q variation at the anaphylatoxin-like region. Second, in healthy White subject MS630, a C-nucleotide deletion at codon-755 led to frameshift mutations in his single C4B gene, which was a private mutation. Third, in European family E94 with multiplex lupus-related mortality and low serum C4 levels, the culprit was a recurrent haplotype with HLA-A30, B18 and DR7 that segregated with two defective C4B genes and identical mutations at the donor splice site of intron-28. Fourth, in East-Asian subject E133P with anti-NMDA receptor encephalitis, the C4B gene had a mutation that changed tryptophan-660 to a stop-codon (W660x), which was present in a haplotype with HLA-DRB1*04:06 and B*15:27. The W660x mutation is recurrent among East-Asians with a frequency of 1.5% but not detectable among patients with SLE. A meticulous annotation of C4 sequences revealed clusters of variations proximal to sites for protein processing, activation and inactivation, and binding of interacting molecules.

The vertebral column is the most common site of osteoporotic fracture in older individuals and in those using long-term glucocorticoids. Vertebral compression fracture leads to significant morbidities such as acute and chronic pain, spinal deformities and neurological complications, resulting in reduced mobility and quality of life. As a previous vertebral compression fracture is a strong risk factor for further fragility fractures and mortality, it should be treated appropriately. This article reviews the management of osteoporotic vertebral compression fracture and provides evidence-based treatment options.

In patients with idiopathic inflammatory myopathy, the presence of the melanoma differentiation-associated gene 5 (MDA5) antibody carries an extremely poor prognosis as a result of the associated interstitial lung disease (ILD) that is often rapidly progressive and refractory to therapies. Management of anti-MDA5 associated ILD is a challenging task as there is a paucity of clinical data and treatment guidelines in the literature. We hereby describe a proposed protocol for a multicenter randomized controlled trial to compare the efficacy of intravenous cyclophosphamide and obinutuzumab in combination with high-dose glucocorticoids and tacrolimus in terms of mortality at six months (primary outcome). The epidemiology, pathogenesis and treatment options of anti-MDA5 associated ILD are briefly reviewed.

Manifestations of neuropsychiatric systemic lupus erythematosus (NPSLE) are heterogeneous. Acute psychosis is an uncommon but well-recognized manifestation of NPSLE. With no specific biomarkers to date, the diagnosis of NPSLE relies on clinical acumen for circumstantial evidence and exclusion of important differential diagnoses. The attribution of psychosis to NPSLE is facilitated by the application attribution models. In particular, the American College of Rheumatology nomenclature, Systemic Lupus International Collaborating Clinics attribution models and Italian algorithm for the attribution of psychosis to NPSLE are revisited. The mainstay of treatment for psychosis attributable to NPSLE is immunosuppression and symptomatic control. In refractory cases, immunomodulatory and emerging biological agents may be considered. This article reviews the diagnostic dilemma, pathogenic mechanisms and treatment of psychosis in SLE patients.

Allopurinol is an effective urate lowering agent but may lead to rare but life-threatening severe cutaneous adverse reactions (SCAR). Genetic predisposition, age, sex, renal function, dosage and concomitant diuretic use are known risk factors of allopurinol related SCAR. Among these factors, HLA-B∗58:01 confers the highest risk. Frequency of the HLA-B∗58:01 allele varies significantly across different ethnic groups. Although the usefulness of HLA-5801 genotyping before initiation of allopurinol has been confirmed by clinical studies, its positive predictive value for SCAR is low because of the low prevalence of HLA-5801 in some localities. Thus, health economic analysis does not consistently show cost-effectiveness of universal screening of HLA-5801 before initiation of allopurinol. However, screening of this genotype in high-risk subjects, including those with renal impairment or advanced age, should be considered on individual basis.

Endometriosis is a common, benign, and hormone-dependent gynaecological disorder that displays altered immunoinflammatory profiles. Myeloid-derived suppressor cells (MDSCs) suppressed immunosurveillance in endometriosis in human and mouse model. Receptor tyrosine kinase inhibitor Sunitinib can induce MDSC apoptosis and suppress the progression of cancer. However, the effects of Sunitinib on MDSCs in endometriosis and the underlying mechanism are not clear. In this study, we employed an animal study of the endometriosis model in mice for treatment of Sunitinib. After syngeneic endometrium transplantation and treatment, endometriotic lesion volume, weight, and histology were compared. Peritoneal fluid, peripheral blood, and bone marrow MDSC subsets and their molecular signaling were monitored by flow cytometry. Peritoneal cytokines were assayed by ELISA. The gene expression profiles of isolated CD11b+Ly6G+Ly6Clo cells were studied by RNA sequencing. We found that Sunitinib significantly decreased the endometriotic lesion size and weight after 1 and 3 weeks, and decreased p-STAT3 activation in MDSCs after 1 week of treatment. In the first week, Sunitinib specifically increased the G-MDSC population in peritoneal fluid but the isolated CD11b+Ly6G+Ly6Clo MDSCs after Sunitinib treatment were presented as mature polynuclear MDSCs, while the control group had immature mononuclear MDSCs. Importantly, we found Sunitinib differentially suppressed gene expressions of immunosuppressive function and differentiation in peritoneal G-MDSCs. Apelin signaling pathway associated genes and inflammation related genes were upregulated, and amino acid metabolism regulator genes were downregulated in bone marrow G-MDSCs. For endometriotic lesions, the PPARG gene governing glucose metabolism and fatty acid storage, which is important for the development of endometriosis was upregulated. In conclusion, Sunitinib inhibited endometriotic lesions, by promoting peritoneal fluid MDSCs maturation and inhibiting the immunosuppressive function. These findings suggest that Sunitinib changed the immune microenvironment and inhibited the development of endometriosis, which has potential therapeutic effects as novel immunotherapy to promote MDSCs maturation, differentiation, and metabolism for the treatment of endometriosis.

Among the inflammatory rheumatic diseases, SLE is associated with the highest risk of herpes zoster reactivation relative to age. The reported incidence of herpes zoster infection in SLE ranges from 6.4 to 91.4/1000 patient-years, with main risk factors being major organ disease, immunosuppressive and biological therapies. Although herpes zoster in SLE is manageable with anti-viral treatment, complications such as superimposed bacterial infection, post-herpetic neuralgia may ensue. The low rate of herpes zoster vaccination in SLE is related to the lack of awareness, fear of the risk of vaccine-induced infection and disease flare, cost, as well as the lack of explicit recommendations of vaccine use for the paucity of data in immunocompromised and younger subjects. The recent availability of the non-live subunit and inactivated herpes zoster vaccines has provided more opportunities for SLE patients to be protected against this viral infection. More clinical trials are clearly needed in SLE to confirm safety, immunogenicity and efficacy of the herpes zoster vaccines.

CD163 is a marker for alternatively activated macrophages, which have been implicated in the pathogenesis of lupus nephritis (LN). In our preliminary screening of urine proteins in LN, urine soluble CD163 (sCD163) was significantly elevated in patients with active LN. To evaluate the potential of sCD163 as a biomarker in LN, urine sCD163 was assayed in patients with active LN, active non-renal lupus patients (ANR), inactive SLE and healthy controls (HC), using ELISA and normalized to urine creatinine. The correlation of urine sCD163 with clinical parameters and renal pathological attributes was further investigated in LN patients with concurrent renal biopsies. A total of 228 SLE patients and 56 HC were included from three cohorts. Results demonstrated that urine sCD163 was significantly elevated in active LN when compared with HC, inactive SLE, or ANR in African-American, Caucasian and Asian subjects (all P < 0.001). In LN patients with concurrent renal biopsies, urine sCD163 was significantly increased in patients with proliferative LN when compared with non-proliferative LN (P < 0.001). Urine sCD163 strongly correlated with SLEDAI, rSLEDAI, activity index (AI) of renal pathology, fibrinoid necrosis, cellular crescents, and interstitial inflammation on biopsies (all P < 0.01). Macrophages, particularly M2 macrophages, the predominant cells expressing CD163 within LN kidneys, represented a potential source of elevated urine sCD163, based on single-cell RNA sequencing analysis. To conclude, urine sCD163 discriminated patients with active LN from other SLE patients and was significantly elevated in proliferative LN. It strongly correlated with concurrent AI and several specific pathological attributes, demonstrating its potential in predicting renal pathology.