The Expression of Toll-like Receptors (TLR7 and TLR9) in Class III and Class IV of Recently Diagnosed Lupus Nephritis with 12-Month Follow-Up.

Renal involvement is an important cause of morbidity and mortality in systemic lupus erythematosus (SLE). The present study included patients with recently diagnosed Class III and Class IV lupus nephritis (LN) treated by Rheumatology who, upon the detection of alterations in their kidney function, were referred to Nephrology for the joint management of both medical specialties. The purpose of this study was to compare the plasma expression of Toll-Like Receptor 7 (TLR7) and TLR9 in healthy control (HC) subjects and newly diagnosed Class III and Class IV LN patients with 12-month follow-ups. The plasma expression of TLR7 and TLR9 proteins was determined by the ELISA method. A significant increase in the expression of TLR7 protein was found in Class III LN in the basal determination compared to the expression in the HC (p = 0.002) and at 12 months of follow-up (p = 0.03) vs. HC. The expression of TLR9 showed a behavior opposite to that of TLR7. TLR9 showed decreased protein expression in LN Class III patients' baseline and final measurements. The result was similar in the basal and final determinations of LN Class IV compared to the expression in HC. A significant decrease in SLEDAI -2K was observed at 12 months of follow-up in patients in Class III (p = 0.01) and Class IV (p = 0.0001) of LN. Complement C3 levels improved significantly at 12-month follow-up in Class IV patients (p = 0.0001). Complement C4 levels decreased significantly at 12-month follow-up in LN Class III compared to baseline (p = 0.01). Anti-DNA antibodies decreased significantly at 12 months of follow-up in Class IV LN (p = 0.01). A significant increase in proteinuria was found at 12 months of follow-up in Class III LN, compared to the baseline determination (p = 0.02). In LN Class IV, proteinuria decreased at 12 months of follow-up compared to baseline (p = 0.0001). Albuminuria decreased at 12 months of follow-up in LN Class IV (p = 0.006). Class IV LN, albuminuria also decreased at 12 months of follow-up (p = 0.009). Hematuria persisted in all patients and the glomerular filtration rate did not change. Three Class IV patients died before 12 months of follow-up from various causes. In conclusion, although the rheumatologic data appeared to improve, the renal function data remained inconsistent. Decreased expression of TLR9 and increased expression of TLR7 could be useful in the early diagnosis of Class III and Class IV LN is correct.

[Treatment of lupus nephritis]. / Prise en charge de la néphropathie lupique en 2023.

Lupus nephritis remains the most frequent severe complication of systemic lupus erythematosus, leading to chronic renal impairment in 20 to 25% of cases. Current treatment is based on the combined use of immunosuppressive treatment and targeted biotherapies to optimize the chances of promptly obtaining and maintaining a complete renal response over the long term. The author discusses these recent advances.

Title: Prise en charge de la néphropathie lupique en 2023. Abstract: La néphropathie lupique reste la complication sévère la plus fréquente du lupus érythémateux disséminé. Elle évolue vers l'insuffisance rénale chronique dans 20 à 25 % des cas. Son traitement moderne repose sur l'utilisation combinée d'un traitement immunosuppresseur et de biothérapies ciblées pour optimiser les chances d'obtenir rapidement et de maintenir au long cours une réponse rénale complète. L'auteur discute ces progrès récents.

A Comprehensive and Practical Approach to the Management of Lupus Nephritis in the Current Era.

Lupus nephritis (LN) is a severe complication of systemic lupus erythematosus (SLE) and is one of the leading causes of morbidity and mortality in patients with SLE. It is estimated that up to 60% of individuals with SLE will develop LN, which can manifest at any stage of a patient's life; however, it commonly emerges early in the course of SLE and tends to exhibit a more aggressive phenotype in men compared to women. Black and Hispanic patients are more likely to progress to kidney failure than white patients. LN is characterized by kidney inflammation and chronic parenchymal damage, leading to impaired kidney function and potential progression to kidney failure. This article provides a comprehensive overview of the epidemiology, pathogenesis, clinical presentation, diagnosis, and management of LN, highlighting the importance of early recognition and treatment of LN to prevent progressive, irreversible kidney damage and improve patient outcomes. Additionally, the article discusses current and emerging therapies for LN, including traditional immunosuppressive agents, biological agents, and novel therapies targeting specific pathways involved in LN pathogenesis, to provide a practical guide for clinicians in properly diagnosing LN and determining a patient-centered treatment plan.

Sex-specific differences in SLE - Significance in the experimental setting of inflammation and kidney damage in MRL-Faslpr mice.

Animal models are an important tool in the research of chronic autoimmune diseases, like systemic lupus erythematosus (SLE). MRL-Faslpr mice are one of different lupus models that develop spontaneously an SLE-like disease with autoantibodies and immune complex deposition that leads into damage of different organs. In contrast to human SLE, both sexes of MRL-Faslpr mice develop a similar autoimmune disease. Due to the sex bias in human and the delayed disease progression in male MRL-Faslpr mice, the majority of studies have been performed in female mice. To determine the suitability of male MRL-Faslpr mice for SLE research, especially with regard to the 3 R-principle and animal welfare, analyses of phenotype, inflammation and damage with focus on kidney and spleen were performed in mice of both sexes. Female mice developed lymphadenopathy and skin lesions earlier as males. At an age of 3.5 month, more immune cells infiltrated kidney and spleen in females compared to males. At the age of 5 months, however, substantially less sex-specific differences were detected. Since other studies have shown differences between both sexes on other manifestations like autoimmune pancreatitis and Sjögren syndrome in MRL-Faslpr mice, the use of male mice as part of 3 R-principle and animal welfare must be carefully considered.

Factors influencing self-management behaviors in persons with lupus nephritis: A cross-sectional study.

Background: Patients with lupus nephritis experience disease symptoms and side effects from treatment. Although self-management behaviors are important in patients with this disease, there is limited research on the factors influencing these behaviors. Objective: This study aimed to examine the factors influencing self-management behaviors in patients with lupus nephritis. Methods: This cross-sectional study was conducted in 240 patients with lupus nephritis at a university hospital in Thailand between August 2019 and December 2020 using a random sampling method. Data were collected using a demographic and clinical characteristic questionnaire, Self-Management Behavior Questionnaire, Self-efficacy for Managing Chronic Disease: A 6-item Scale, Knowledge about Lupus Nephritis Questionnaire, Family Support Scale, Social Networks in Adult Life Questionnaire, and Memorial Symptom Assessment Scale for Lupus Nephritis. Descriptive statistics and multiple linear regression analyses were employed. Results: The participants reported a moderate level of self-management behaviors. Multiple regression analyses revealed that disease duration, income, symptoms, self-efficacy, knowledge, family support, social networks, and classes of lupus nephritis significantly explained 21% of the variance in self-management behaviors (R2 = 0.21; F(8,231) = 7.73; p <0.001). Family support (ß = 0.32, p <0.001) and symptoms (ß = -0.23, p <0.001) were significant determinants of self-management behaviors in patients with lupus nephritis. Conclusion: The findings provide valuable insight for nurses to better understand the factors influencing self-management behaviors in patients with lupus nephritis. Patients with low family support and high symptom severity may face difficulty in performing self-management behaviors. Nurses should pay more attention to these patients and provide family-based interventions to optimize self-management behaviors in this population.

Understanding the relationship between HCV infection and progression of kidney disease.

Hepatitis C virus (HCV) can cause a range of kidney diseases. HCV is the primary cause of mixed cryoglobulinaemia, which leads to cryoglobulinaemic vasculitis and cryoglobulinaemic glomerulonephritis (GN). Patients with acute cryoglobulinaemic vasculitis often exhibit acute kidney disease due to HCV infection, which typically progresses to acute kidney injury (AKI). HCV also increases the risk of chronic kidney disease (CKD) and the likelihood of developing end-stage renal disease (ESRD). Currently, direct-acting antiviral agents (DAAs) can be used to treat kidney disease at different stages. This review focuses on key findings regarding HCV and kidney disease, discusses the impact of DAAs, and highlights the need for further research and treatment.

Investigation of ferroptosis-associated molecular subtypes and immunological characteristics in lupus nephritis based on artificial neural network learning.

BACKGROUND: Lupus nephritis (LN) is a severe complication of systemic lupus erythematosus (SLE) with poor treatment outcomes. The role and underlying mechanisms of ferroptosis in LN remain largely unknown. We aimed to explore ferroptosis-related molecular subtypes and assess their prognostic value in LN patients. METHODS: Molecular subtypes were classified on the basis of differentially expressed ferroptosis-related genes (FRGs) via the Consensus ClusterPlus package. The enriched functions and pathways, immune infiltrating levels, immune scores, and immune checkpoints were compared between the subgroups. A scoring algorithm based on the subtype-specific feature genes identified by artificial neural network machine learning, referred to as the NeuraLN, was established, and its immunological features, clinical value, and predictive value were evaluated in patients with LN. Finally, immunohistochemical analysis was performed to validate the expression and role of feature genes in glomerular tissues from LN patients and controls. RESULTS: A total of 10 differentially expressed FRGs were identified, most of which showed significant correlation. Based on the 10 FRGs, LN patients were classified into two ferroptosis subtypes, which exhibited significant differences in immune cell abundances, immune scores, and immune checkpoint expression. A NeuraLN-related protective model was established based on nine subtype-specific genes, and it exhibited a robustly predictive value in LN. The nomogram and calibration curves demonstrated the clinical benefits of the protective model. The high-NeuraLN group was closely associated with immune activation. Clinical specimens demonstrated the alterations of ALB, BHMT, GAMT, GSTA1, and HAO2 were in accordance with bioinformatics analysis results, GSTA1 and BHMT were negatively correlated with the severity of LN. CONCLUSION: The classification of ferroptosis subtypes and the establishment of a protective model may form a foundation for the personalized treatment of LN patients.

Comparison of the Quantitative Values of Peripapillary, Macular and Choriocapillary Microvascular Structures According to the Presence of Lupus Nephritis in Patients with Systemic Lupus Erythematosus.

PURPOSE: To determine whether there are quantitative changes in macular, choriocapillary, and peripapillary microvascular structures using optical coherence tomography angiography (OCTA) due to the presence of lupus nephritis (LN) in patients with systemic lupus erythematosus (SLE) and to investigate the correlation between these quantitative values and disease duration. METHODS: Fifty -five patients followed up in the rheumatology clinic with an SLE diagnosis were evaluated. As the control group, 61 eyes of 61 age- and gender-matched healthy individuals were included. The patients with SLE were further divided into two groups: those with LN (29 eyes) and those without LN (26 eyes). Macular, choriocapillary, and peripapillary microvascular structures were quantitatively analyzed with OCTA and compared between the three study groups. A correlation analysis of the measured quantitative values and disease duration was also performed. RESULTS: In macular microvascular (MMV) analysis, the vessel densities (VDs) of the superficial capillary plexus (SCP) decreased in both SLE groups, while those of the deep capillary plexus (DCP) decreased only in the SLE group with LN. The foveal density significantly decreased in the SLE group with LN compared to the control group, there were no significant differences in terms of the radial peripapillary capillary VDs or the choriocapillaris flow area. Disease duration was not correlated with any of the quantitative parameters measured by OCTA in either SLE group. CONCLUSIONS: Identifying differences in retinal microvascular circulation in SLE patients with kidney damage helps predict possible nephropathy and therefore guides the treatment process of this patient.

Ferroptosis and secondary nephrosis. / é“æ­»äº¡ä¸Žç»§å‘æ€§è‚¾è„ç— .

Secondary nephrosis is a series of chronic kidney diseases secondary to other underlying diseases, mainly manifesting as structural and functional abnormalities of the kidneys and metabolic disorders. It is one of the important causes of end-stage renal disease, with high morbidity and significant harm. Iron is an essential metal element in human cells, and ferroptosis is a non-traditional form of iron-dependent cell death, and its main mechanisms include iron accumulation, lipid metabolism disorders, abnormal amino acid metabolism, and damage to the antioxidant system. Recently studies have found that ferroptosis is involved in the occurrence and progression of secondary nephrosis, and the mechanism of ferroptosis in different secondary nephrosis vary. Therefore, an in-depth and systematic understanding of the association between ferroptosis and secondary nephrosis, as well as their specific regulatory mechanisms, can provide a theoretical basis for the diagnosis, prevention, treatment, and prognosis assessment of secondary nephrosis, laying the foundation for exploring new clinical therapeutic targets for secondary nephrosis.

Imbalance of programmed cell death patterns mediated by dendritic cell subsets in systemic lupus erythematosus and lupus nephritis. / æ ‘çªçŠ¶ç»†èƒžäºšç¾¤ä»‹å¯¼ç³»ç»Ÿæ€§çº¢æ–‘ç‹¼ç–®å’Œç‹¼ç–®è‚¾ç‚Žçš„ç¨‹åºæ€§ç»†èƒžæ­»äº¡æ¨¡å¼å¤±è¡¡ï¼ˆè‹±æ–‡ï¼‰.

OBJECTIVES: Abnormal programmed cell death in immune cells is associated with autoimmune diseases, but the patterns of programmed cell death in systemic lupus erythematosus (SLE) and especially lupus nephritis (LN) remain unclear. This study aims to explore the association between SLE, LN, and immune cell death patterns. METHODS: Bulk RNA sequencing (bulk RNA-seq) and single-cell RNA sequencing (scRNA-seq) data were downloaded from the Gene Expression Omnibus (GEO) database. Bioinformatic analysis was conducted to explore the expression levels of genes related to 3 cell death patterns in peripheral blood mononuclear cells of SLE patients. Key cell subsets involved in the imbalance of cell death patterns were identified through scRNA-seq. Immunofluorescence was used to detect the expression levels of receptor interacting serine/threonine kinase 3 (RIPK3), mixed-lineage kinase domain-like protein (MLKL), phosphorylated MLKL (pMLKL), caspase 1 (CASP1), CD1c molecule (CD1C), C-type lectin domain containing 9A (CLEC9A), and X-C motif chemokine receptor 1 (XCR1) in dendritic cells (DC). scRNA-seq was performed on kidney tissues collected from LN patients and healthy controls (HC) at the Third Xiangya Hospital of Central South University, followed by bioinformatic analysis to identify key cell subsets involved in the imbalance of cell death patterns. Pseudotime analysis and ligand-receptor analysis were used to explore the differentiation direction and cell communication of different DC subsets. Transient transfection was used to transfect RAW264.7 cells with empty plasmid, empty plasmid+dsDNA (HSV-DNA), empty plasmid+200 µmol/L tert-butyl hydroperoxide (TBHP), stimulator of interferon genes (STING) shRNA plasmid, STING shRNA plasmid+dsDNA (HSV-DNA), and STING shRNA plasmid+200 µmol/L TBHP. Annexin V-mCherry and SYTOX Green staining were used to detect cell death in each group. Western blotting was used to detect the activation of CASP1, gasdermin D (GSDMD), RIPK3, and MLKL in each group. RESULTS: Bioinformatic analysis showed an imbalance in 3 cell death patterns in SLE and LN patients: Pro-inflammatory pyroptosis and necroptosis were activated, while anti-inflammatory apoptosis was inhibited. The key cell subsets involved were DC subsets, particularly focusing on CLEC9A+cDC1. Immunofluorescence results showed that the expression levels of RIPK3, MLKL, and CASP1 in DCs were higher in the SLE group compared to the HC group. pMLKL and CASP1 expression levels in renal cDC1 marked by CLEC9A and XCR1 were higher in the LN group than in the HC group. Pseudotime analysis and ligand-receptor analysis suggested that the CLEC9A+cDC1 subset in LN kidney tissues originated from peripheral circulation. Annexin V-mCherry and SYTOX Green staining results showed that the number of dead cells decreased in the STING shRNA transfection group compared to the empty plasmid group in RAW264.7 cells. Western blotting results showed that the activation of CASP1, GSDMD, RIPK3, and MLKL was decreased in the STING shRNA transfection group compared to the empty plasmid group. CONCLUSIONS: This study provides novel insights into the role of CLEC9A+cDC1 in the imbalance of cell death patterns in SLE and LN.

Clinicopathological phenotype and outcomes of NCAM-1+ membranous lupus nephritis.

INTRODUCTION: No studies explored the long-term outcomes of neural cell adhesion molecule 1 (NCAM1) associated membranous lupus nephritis (MLN) patients. METHOD: We performed immunohistochemical studies on kidney biopsy specimens against NCAM1 in consecutive MLN patients. The clinical and histopathological characteristics and outcomes of cases of NCAM1 associated MLN patients are described and compared with NCAM1 negative patients. In addition, we detected serum circulating anti-NCAM1 antibodies through western blotting and indirect immunofluorescence assays. RESULTS: Among 361 MLN cases, 18 (5.0%) were glomerular NCAM1-positive. NCAM1 positive MLN patients were older [35 years (IQR 27-43) versus 28 (22-37); P = 0.050) and had lower systemic lupus erythematosus disease activity index [11 (IQR 8-12) versus 14 (10-18); P = 0.007], serum creatinine [60 µmol/L (IQR 50-70) versus 70 (54-114); P = 0.029], activity index [3 (IQR 2-6) versus 6 (3-9); P = 0.045] at kidney biopsy compared with NCAM1 negative patients. The percentage of positive anti-Sjogren's syndrome related antigen A antibodies in NCAM1 positive patients was significantly greater (83.3% versus 58.2%; P = 0.035) than in the NCAM1 negative patients. However, no evidence of neuropsychiatric disorders was found in these 18 patients. There were no significant differences in the treatment response and the risk of end stage renal diseases between NCAM1 positive and negative groups (P = 0.668 and P = 0.318, respectively). But the risk of death was much higher in the NCAM1 positive group than the NCAM1 negative group (27.8% vs. 8.1%, P = 0.007). Moreover, the risk of death was also much higher in the NCAM1 positive group than the matched NCAM1 negative group (Log-rank P = 0.013). Additionally, circulating anti-NCAM1 antibodies can be detected in 1/5 (20%) patients who had serum available. CONCLUSION: The prevalence of NCAM1 positivity was 5.0% in our cohort of MLN and the high mortality in these subgroup patients are needed to validate in future studies.

An Atypical Initial Presentation of Systemic Lupus Erythematous With Bilateral Lower Extremity Edema and Unilateral Pleural Effusion.

Systemic lupus erythematosus (SLE) is an autoimmune condition more commonly observed in women of childbearing age. The most commonly reported initial presentations were fatigue, arthritis, and skin manifestations. However, due to the involvement of a variety of organs, diagnosis remains a challenge for physicians. Our patient is a 48-year-old lady who presented with severe bilateral lower extremity edema with non-resolving right lower lobe pneumonia and ipsilateral exudative pleural effusion. Her leg swelling was not responding to diuretics, and her pneumonia was not improving following a course of antibiotics. This unusual presentation prompted an autoimmune workup, which later revealed a diagnosis of SLE with class 5 lupus nephritis. Pleuritis, exudative pleural effusion, and lupus nephritis have been associated with autoimmune disorders in the literature, but this is an uncommon initial presentation in SLE without other clinical manifestations. Our case report highlights the challenges in the diagnosis of an atypical case of SLE and the need to maintain high clinical suspicion for SLE, especially in female patients with multiorgan involvement.

Acute-Onset Blindness in a Patient Diagnosed With Myelin Oligodendrocyte Glycoprotein Antibody Disease (MOG-AD): A Case Report.

Myelin oligodendrocyte glycoprotein antibody disease (MOG-AD) poses a diagnostic challenge, often masquerading as other neurological disorders such as multiple sclerosis and aquaporin-4-positive neuromyelitis optica spectrum disorder. The deceptive clinical similarities demand a nuanced approach to differentiate these conditions effectively. This entails an extensive evaluation encompassing a meticulous medical history, advanced magnetic resonance imaging (MRI), cerebrospinal fluid analysis, and serum studies. In this context, we present a compelling case involving a 28-year-old Hispanic female with a history of migraine headache. She sought medical attention due to acute peripheral vision loss, ultimately diagnosed as MOG-AD through a comprehensive clinical assessment coupled with specific diagnostic tests. This case underscores the critical importance of precision in diagnostic procedures to ensure accurate identification and subsequent tailored treatment for MOG-AD, avoiding potential pitfalls associated with its resemblance to other neurological disorders.

Does the esv3587290 Copy Number Variation in the VANGL1 Gene Differ as a Genetic Factor for Developing Nephritis in Mexican Childhood-Onset Systemic Lupus Erythematosus Patients?

A ~3-kb deletion-type DNA copy number variation (CNV, esv3587290) located at intron 7 of the VANGL1 gene (1p13.1, MIM*610132) has been proposed as a genetic factor in lupus nephritis (LN) development in adult systemic lupus erythematosus (SLE) patients across European-descent populations, but its replication in other ethnicities has been inconsistent and its association with LN in childhood-onset SLE (cSLE) remains unknown. Here, we performed an exploratory association study in a sample of 66 unrelated cSLE Mexican patients (11 males, 55 females; ages 7.8 to 18.6 years). Two stratified groups were compared: cSLE patients with (N = 39) or without (N = 27) LN, as diagnosed by renal biopsy (N = 17), proteinuria (N = 33), urinary protein-creatinine ratio > 0.2 (N = 34), and erythrocyturia and/or granular casts in urinary sediment (N = 16). For esv3587290 CNV genotyping, we performed an end-point PCR assay with breakpoint confirmation using Sanger sequencing. We also determined the allelic frequencies of the esv3587290 CNV in 181 deidentified ethnically matched individuals (reference group). The obtained genotypes were tested for Hardy-Weinberg equilibrium using the χ2 test. Associations between LN and esv3587290 CNV were tested by calculating the odds ratio (OR) and using Pearson's χ2 tests, with a 95% confidence interval and p ≤ 0.05. The esv3587290 CNV allele (OR 0.108, 95% CI 0.034-0.33, p = 0.0003) and the heterozygous genotype (OR 0.04, 95% CI 0.119-0.9811, p = 0.002) showed a significant protective effect against LN development. Finally, we characterized the precise breakpoint of the esv3587290 CNV to be NG_016548.1(NM_138959.3):c.1314+1339_1315-897del in our population. This report supports the notion that a broad genetic heterogeneity underlies the susceptibility for developing LN.

Lupus mesenteric vasculitis with gastrointestinal bleeding as the primary manifestation: a case report.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease where the body loses tolerance to its own antigens, particularly nuclear antigens. Abnormal responses from T and B cells lead to the production of autoantibodies and the formation of immune complexes in tissues, triggering complement activation, inflammation, and irreversible organ damage. SLE can affect any part of the body, resulting in diverse clinical symptoms. One rare manifestation of SLE is lupus mesenteric vasculitis (LMV), which presents with vague symptoms, abnormal laboratory findings, and specific imaging features. LMV, although uncommon, can progress to severe complications such as bowel perforation, haemorrhage, and even mortality. Here, we report a case of LMV with the involvement of multiple organ systems (including mucocutaneous, musculoskeletal, serosal cavities, and haematological systems), presenting initially with life-threatening intractable gastrointestinal bleeding, and complicated by severe pulmonary infection. By sharing this case, we aim to enhance clinicians' confidence in managing critical SLE cases and raise awareness about disease surveillance.

Integrative analysis of COL6A3 in lupus nephritis: insights from single-cell transcriptomics and proteomics.

Introduction: Lupus nephritis (LN), a severe complication of systemic lupus erythematosus (SLE), presents significant challenges in patient management and treatment outcomes. The identification of novel LN-related biomarkers and therapeutic targets is critical to enhancing treatment outcomes and prognosis for patients. Methods: In this study, we analyzed single-cell expression data from LN (n=21) and healthy controls (n=3). A total of 143 differentially expressed genes were identified between the LN and control groups. Then, proteomics analysis of LN patients (n=9) and control (SLE patients without LN, n=11) revealed 55 differentially expressed genes among patients with LN and control group. We further utilizes protein-protein interaction network and functional enrichment analyses to elucidate the pivotal role of COL6A3 in key signaling pathways. Its diagnostic value is evaluate through its correlation with disease progression and renal function metrics, as well as Receiver Operating Characteristic Curve (ROC) analysis. Additionally, immunohistochemistry and qPCR experiments were performed to validate the expression of COL6A3 in LN. Results: By comparison of single-cell and proteomics data, we discovered that COL6A3 is significantly upregulated, highlighting it as a critical biomarker of LN. Our findings emphasize the substantial involvement of COL6A3 in the pathogenesis of LN, particularly noting its expression in mesangial cells. Through comprehensive protein-protein interaction network and functional enrichment analyses, we uncovered the pivotal role of COL6A3 in key signaling pathways including integrin-mediated signaling pathways, collagen-activated signaling pathways, and ECM-receptor interaction, suggesting potential therapeutic targets. The diagnostic utility is confirmed by its correlation with disease progression and renal function metrics of the glomerular filtration rate. ROC analysis further validates the diagnostic value of COL6A3, with the area under the ROC values of 0.879 in the in-house cohort, and 0.802 and 0.915 in tubular and glomerular external cohort samples, respectively. Furthermore, immunohistochemistry and qPCR experiments were consistent with those obtained from the single-cell RNA sequencing and proteomics studies. Discussion: These results proved that COL6A3 is a promising biomarker and therapeutic target, advancing personalized medicine strategies for LN.

Anti-C1q antibodies: a biomarker for diagnosis and management of lupus nephritis. A narrative review.

Nephritis is a frequent and severe complication of Systemic Lupus Erythematous (SLE). The clinical course of lupus nephritis (LN) is usually characterized by alternating phases of remission and exacerbation. Flares of LN can lead to deterioration of kidney function, necessitating timely diagnosis and therapy. The presence of autoantibodies against C1q (anti-C1qAb) in the sera of SLE patients has been reported in various studies. Some research suggests that the presence and changes in the titer of anti-C1qAb may be associated with the development of LN, as well as with LN activity and renal flares. However, the exact role of anti-C1qAb in LN remains a subject of debate. Despite variability in the results of published studies, anti-C1qAb hold promise as noninvasive markers for assessing LN activity in SLE patients. Measuring anti-C1qAb levels could aid in diagnosing and managing LN during periods of both inactive disease and renal flares. Nevertheless, larger controlled trials with standardized laboratory assays are necessary to further establish the utility of anti-C1qAb in predicting the reactivation and remission of LN and guiding treatment strategies.

Hospital Healthcare Resource Utilization and Associated Hospital Costs of Patients With Lupus Nephritis in China: A National Administrative Claim Database Study.

OBJECTIVES: Assess hospital healthcare resource utilization (HCRU) and associated hospital costs of patients with lupus nephritis (LN) in China and compare these outcomes with a systemic lupus erythematosus (SLE) cohort (SLE with/without LN) as well as exploring the effect of end-stage kidney disease (ESKD). METHODS: This retrospective administrative claims-based analysis identified patients with SLE and SLE with LN from China using diagnosis codes and keywords. Patients with LN were subcategorized by presence of ESKD. Outcomes included all-cause and disease-specific HCRU (defined as healthcare visits including inpatient and outpatient visits) and medical costs (in 2022 US dollars). RESULTS: In total, 3645 patients with SLE were included, of whom 404 (11%) had LN. Among those with LN, 142 (35%) had ESKD. Median (interquartile range) all-cause healthcare visits per patient per month (PPPM) was significantly greater for patients with LN (2.08 [4.01]) vs SLE (0.92 [1.64]; P < .0001). Patients with LN and ESKD (3.00 [4.18]) had numerically more all-cause healthcare visits PPPM compared with LN patients without ESKD (1.50 [3.45]). Median all-cause costs PPPM were significantly greater among patients with LN ($287.46 [477.15]) vs SLE ($113.09 [267.39]; P < .0001) and numerically higher for patients with LN and ESKD ($466.29 [958.90]) vs LN without ESKD ($223.50 [319.56]). CONCLUSIONS: Chinese patients with LN had greater HCRU and hospital healthcare costs compared with the general SLE cohort. This burden was higher for those with ESKD. These data highlight the substantial HCRU among patients with LN in China, especially those with ESKD, suggesting the need for early diagnosis and timely management of LN to mitigate the economic burden.

[NETosis in lupus nephritis].

AIM: To evaluate the levels of MPO-DNA complex in patients with systemic lupus erythematosus (SLE) and its association with the presence of lupus nephritis (LN). MATERIALS AND METHODS: The study included 77 patients with SLE, of whom 30 had SLE without anti phospholipid syndrome (APS), 47 had SLE with APS, and 20 were healthy individuals serving as the control group. The MPO-DNA complex in the serum was investigated using ELISA. RESULTS: The levels of MPO-DNA complex in serum were significantly higher in patients with SLE compared to healthy controls (p=0.001). Among the patients with SLE, 30 (39%) had elevated levels of MPO-DNA complex. The presence of elevated MPO-DNA complex was significantly associated with the presence of a history of LN (p=0.009). Moreover, among the patients included in the study, 20 had active LN, and patients with elevated MPO-DNA complex levels were more likely to have active LN than patients without elevated MPO-DNA complex concentrations [12 (40%) of 30 vs 8 (17%) of 47, χ2=5.029; p=0.034]. An association was found between elevated levels of MPO-DNA complex and the presence of proteinuria, hematuria, cellular hematic/granular casts and aseptic leukocyturia. A direct correlation of MPO-DNA complex with SLEDAI-R was found in patients with active LN (rs=0.497; p=0.026). CONCLUSION: Elevated levels of MPO-DNA complex were detected in 39% of patients with SLE. These patients had a higher prevalence of LN in their medical history and at the time of inclusion in the study. The correlation between MPO-DNA complex levels and the activity of LN according to SLEDAI-R indicates the potential role of MPO-DNA complex as a biomarker for assessing the activity of renal damage in SLE.

Risk factors for acute kidney injury and kidney relapse in patients with lupus podocytopathy.

Background: Patients with lupus podocytopathy show a high incidence of acute kidney injury (AKI) and relapse, but the risk factors and mechanisms were unclear. This study analysed the clinicopathological features and risk factors for AKI and relapse in lupus podocytopathy patients. Methods: The cohort of lupus podocytopathy was generated by screening the biopsies of patients with lupus nephritis (LN) from 2002 to 2022 and was divided into the mild glomerular lesion (MGL) and focal segmental glomerulosclerosis (FSGS) groups based on glomerular morphological characteristics. The acute (ATI) and chronic (CTI) tubulointerstitial lesions were semi-quantitatively scored. Logistic and Cox regressions were employed to identify the risk factors for AKI and relapse, respectively. Results: Among 6052 LN cases, 98 (1.6%) were diagnosed as lupus podocytopathy, with 71 in the MGL group and 27 in the FSGS group. All patients presented with nephrotic syndrome and 33 (34.7%) of them had AKI. Seventy-seven (78.6%) patients achieved complete renal response (CRR) within 12 weeks of induction treatment, in which there was no difference in the CRR rate between glucocorticoid monotherapy and combination therapy with glucocorticoids plus immunosuppressants. Compared with the MGL group, patients in the FSGS group had significantly higher incidences of hypertension and haematuria; in addition, they had higher Systemic Lupus Erythematosus Disease Activity Index 2000, ATI and CTI scores but a significantly lower CRR rate. Urinary protein ≥7.0 g/24 h and serum C3 ≤0.750 g/l were independent risk factors for AKI. During a median follow-up of 78 months, 57 cases (60.0%) had relapse and none reached the kidney endpoint. Failure to achieve CRR within 12 weeks, maintenance with glucocorticoid monotherapy and AKI at onset were independent risk factors for kidney relapse. Conclusions: In this study, histological subtypes of lupus podocytopathy were found to be associated with clinical features and treatment response. In addition, several risk factors associated with AKI occurrence and kidney relapse were identified.