Progranulin mediates the onset of pristane induced systemic lupus erythematosus.

BACKGROUNDS: Progranulin (PGRN) is a growth factor-like molecule with diverse roles in homeostatic and pathogenic processes including the control of immune and inflammatory responses. Pathogenic inflammation is a hallmark of systemic lupus erythematosus (SLE) and elevated serum levels of PGRN has been evaluated as a biomarker of disease activity in SLE. However, the role of PGRN in SLE has not been fully investigated. This study is aimed to determine the potential involvements of PGRN in SLE. METHODS: Wild type (WT) and PGRN knockout (PGRN-/-) C57BL/6 mice received intraperitoneal injection of pristane for induction of a murine model of SLE. Sera were collected every biweekly and levels of anti-dsDNA antibody, IgG, and inflammatory factors were measured. Mice were sacrificed 5 months later and the renal lesions, as well as the proportions of T cell subtypes in the spleen were analyzed. RESULTS: Following exposure to pristane, PGRN-/- mice generated significantly lower levels of anti-dsDNA antibody and IgG relative to WT mice. PGRN-/- mouse kidneys had less IgG and collagen deposition compared with WT mice after pristane injection. CONCLUSION: The results indicate that PGRN participates in inflammatory response and renal damage in pristane induced SLE models, suggesting that PGRN mediates the onset of SLE.

Converging pathways: acquired von Willebrand disease in systemic lupus erythematosus with antiphospholipid antibodies presenting with persistent menstrual bleeding.

We present a case of a woman in her 20s with inadequately treated systemic lupus erythematosus (SLE). She presented with heavy menstrual bleeding, along with nasal and gum bleeding worsening over 3 months. There was no bleeding history in her family, childhood, dental procedures or childbirth. Evaluation ruled out structural causes, revealing prolonged activated partial thromboplastin time (incomplete correction on mixing studies), normal prothrombin time, moderate thrombocytopenia, and lupus anticoagulant and anti-phosphatidylserine/prothrombin antibody positivity twice, 12 weeks apart. Further evaluation showed very low von Willebrand factor (vWF) levels (<5%). She was treated with pulse methylprednisolone for 3 days, resulting in complete symptom resolution and improvement in vWF levels to 130%. The absence of bleeding history, family history, presence of very low vWF and its response to corticosteroids led to a diagnosis of acquired vWF syndrome as the cause of mucosal bleeding in an SLE patient with concomitant positive antiphospholipid antibody. She was discharged on hydroxychloroquine, mycophenolate mofetil and tapering oral corticosteroids.

Association between systemic lupus erythematosus and autoimmune thyroid dysfunction in pediatric population: a single center experience.

BACKGROUND: Systemic Lupus Erythematosus (SLE) patients are more likely than the general population to suffer from thyroid illness. The major goal was to assess the thyroid dysfunctions due to immunological factors in Egyptian SLE children and how they are related to the course and severity of the illness. METHODS: Fifty children and adolescents with SLE are included in this cross-sectional observational study. Every patient underwent a thorough physical examination and a comprehensive history taking. An enzyme-linked immunosorbent assay (ELISA) approach was used to evaluate the thyroid profile, anti-thyroglobulin (Anti-TG), and anti-thyroid peroxidase (anti-TPO) antibodies. RESULTS: Of the 50 patients, the female: male ratio (F: M = 7:1) was 44 females and 6 males (12%). They were between the ages of 5 and 17. Out of the patients, thirty-two (64%) had thyroid dysfunctions, 19 (38%) had euthyroid sick syndrome, ten (20%) had overt hypothyroidism, three (6%) had subclinical hypothyroidism, and none had hyperthyroidism. Of the 50 patients, one (2%) had increased anti-TPO, whereas all other patients had normal anti-TG levels. A statistically significant negative correlation (p-value 0.007) was seen between the disease duration and free thyroxine (FT4). Furthermore, a significant negative correlation (p-values 0.015 and 0.028) was found when comparing the disease duration with thyroid antibodies (anti-TG and anti-TPO). CONCLUSION: In Juvenile Systemic Lupus Erythematosus (JSLE), thyroid dysfunctions can be identified. The disease duration but not its activity was significantly correlated with thyroid antibodies. For children with JSLE, thyroid function testing should be done on a regular basis. It is preferable to carry out additional thyroid antibody tests when necessary.

Fever, convulsions, and rash: a case report of neonatal lupus erythematosus with macrophage activation syndrome.

Neonatal lupus erythematosus (NLE) is a rare acquired autoimmune disease associated with the entry of maternal antibodies into the fetal circulation via the placenta during pregnancy. Macrophage activation syndrome (MAS) is a severe hyperinflammatory disease. Herein, we present a case of NLE with MAS accompanied by fever, convulsions, and rash. High-dose gamma globulin and non-shock doses of steroids can be used as a first-line treatment for NLE with MAS. Fever can be a clinical manifestation of NLE, especially cutaneous lupus. Rash recession could be used to judge whether the disease is effectively controlled by treatment.

Case Report: p40 phox deficiency underlying pediatric-onset systemic lupus erythematosus.

Introduction: Systemic lupus erythematosus is a multi-faceted autoimmune disorder of complex etiology. Pre-pubertal onset of pediatric systemic lupus erythematosus (pSLE) is uncommon and should raise suspicion for a genetic driver of disease. Autosomal recessive p40 phox deficiency is a rare immunologic disorder characterized by defective but not abolished NADPH oxidase activity with residual production of reactive oxygen species (ROS) by phagocytic cells. Case presentation: We report the case of a now 18-year-old female with pSLE onset at 7 years of age. She presented with recurrent fever and malar rash. Aspects of her immune dysregulation over time have included typical pSLE features including production of autoantibodies, hematologic manifestations, and hypocomplementemia, as well as chronic suppurative skin lesions and recurrent infections. Genetic analysis revealed biallelic pathogenic variants in NCF4 resulting in p40 phox deficiency. Comprehensive NADPH oxidase activity studies confirmed significantly decreased production of reactive oxygen species, confirming the cellular phenotype seen in p40 phox deficient patients. Conclusions: Here, we present a patient with pSLE harboring biallelic variants in NCF4. Our patient represents a unique clinical presentation of severe onset autoimmunity in the setting of a rare inborn error of immunity affecting NADPH oxidase activity. This case underscores the need to consider genetic causes of pSLE in cases of pre-pubertal onset and atypical disease.

Unlocking therapeutic potential: Targeting lymphocyte activation Gene-3 (LAG-3) with fibrinogen-like protein 1 (FGL1) in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) represents an autoimmune disorder that affects multiple systems. In the treatment of this condition, the focus primarily revolves around inflammation suppression and immunosuppression. Consequently, targeted therapy has emerged as a prevailing approach. Currently, the quest for highly sensitive and specifically effective targets has gained significant momentum in the context of SLE treatment. Lymphocyte activation gene-3 (LAG-3) stands out as a crucial inhibitory receptor that binds to pMHC-II, thereby effectively dampening autoimmune responses. Fibrinogen-like protein 1 (FGL1) serves as the principal immunosuppressive ligand for LAG-3, and their combined action demonstrates a potent immunosuppressive effect. This intricate mechanism paves the way for potential SLE treatment by targeting LAG-3 with FGL1. This work provides a comprehensive summary of LAG-3's role in the pathogenesis of SLE and elucidates the feasibility of leveraging FGL1 as a therapeutic approach for SLE management. It introduces a novel therapeutic target and opens up new avenues of therapeutic consideration in the clinical context of SLE treatment.

Screening for autoimmune diseases in apparently healthy antinuclear antibody positive individuals.

Background: Anti-nuclear antibodies (ANA) assessed by immunofluorescence (IF) microscopy are associated with systemic autoimmune rheumatic diseases (SARD) and can be detected years before onset of clinical symptoms. Recent data indicate dysregulation of the immune system with increased levels of proinflammatory cytokines, including type I interferons (IFN), in ANA-positive versus ANA-negative individuals. Herein, the aims were to investigate IF-ANA, ANA fine specificities, and IFN-α protein levels in relation to self-reported symptoms, as well as clinical signs, of SARD in a large group of healthy blood donors (HBD). Methods: Sera from 825 HBD (48.8% females) were included. IF-ANA was assessed, using HEp-2 cells, according to the routine at the accredited laboratory of Clinical Immunology, Linköping University Hospital. All samples were analyzed for IgG-ANA fine specificities using addressable laser bead assay (ALBIA) at the same laboratory. IFN-α was determined using ELISA. Antibody-positive individuals, and their sex- and age-matched antibody-negative controls, were asked to fill a questionnaire regarding symptoms associated with SARD. Results: In total, 130 HBD (15.8%) were positive with IF-ANA and/or ALBIA. Anti-U1RNP was significantly more common among women. Generally, self-reported symptoms correlated poorly with IF-ANA and/or ALBIA results. Two females with high levels of Ro60/SSA, Ro52/SSA and IFN-α reported mild sicca symptoms and were diagnosed with Sjögren's disease after clinical evaluation. Conclusion: A considerable proportion of apparently HBD are autoantibody positive, but without clear association to self-reported symptoms. Nevertheless, the combination of autoantibodies, relevant symptoms and high IFN-α levels identified the small proportion of individuals with SARD in the study population.

The anti-mCRP199-206 antibodies aggravate tubulointerstitial lesions in lupus nephritis.

Tubulointerstitial lesions could also be prominent in lupus nephritis, and the pathogenesis of tubulointerstitial lesions may be different from glomerular lesions. Previous studies have showed that plasma antibodies against modified /monomeric C-reactive protein (mCRP) are associated with renal tubulointerstitial lesions in patients with lupus nephritis, and amino acid (aa) 199-206 was one of the major epitopes of mCRP. However, the role of anti-mCRP199-206 antibodies in the pathogenesis of tubulointerstitial lesions in lupus nephritis is unknown. A total of 95 patients with renal biopsy-proven lupus nephritis were enrolled in this study. Plasma levels of anti-mCRP199-206 antibodies were screened by enzyme-linked immunosorbent assay (ELISA). A lupus prone mouse model was immunized using peptides mCRP199-206 to explore the potential role of anti-mCRP199-206 antibodies in tubulointerstitial lesions. The mechanism of anti-mCRP199-206 antibodies damage to renal tubular epithelial cells was investigated in vitro. Plasma antibodies against mCRP199-206 were associated with renal tubulointerstitial lesions and prognosis in patients with lupus nephritis. Immunization with peptides mCRP199-206 in lupus prone mice could aggravate tubulointerstitial lesions and drive tubulointerstitial inflammation and fibrosis. Anti-mCRP 199-206 antibodies could activate the TGF-ß1/Smad3 signal pathway and induce tubular damage by binding with CRP. Circulating antibodies against mCRP199-206 could be a biomarker to reveal tubulointerstitial lesion, and participate in the pathogenesis of tubulointerstitial lesions, which might provide a potential therapeutic target for lupus nephritis.

Elevated toll-like receptor 9 is associated with disease severity and kidney involvement in systemic lupus erythematosus.

OBJECTIVES: Systemic lupus erythematosus (SLE) is associated with the activation of both innate and adaptive immune system. Infection is a significant environmental factor that is responsible for the development of SLE. Toll-like receptors (TLRs) are responsible for recognizing pathogens, and the expression of TLRs has been found to differ in SLE patients. Additionally, various infections have been reported to influence TLR expression. This study aimed to explore the relationship between TLRs and the onset, severity, and symptoms of SLE in the eastern Indian population. METHODS: The study included 70 SLE patients and a control group matched for age and sex. RT-PCR was used to evaluate mRNA expression of TLRs 2, 4, 7, and 9. Statistical analyses were performed using GraphPad Prism software v.10.2.3. RESULTS: Patients with SLE expressed significantly higher levels of TLR2 (p < 0.0001) and TLR9 (p = 0.012) than healthy controls. In lupus nephritis, TLR9 expression was higher than in SLE patients without kidney involvement (p = 0.037). Furthermore, a significant relationship was found between TLR9 expression and systemic lupus erythematosus disease activity index (SLEDAI) scores (p < 0.0001, Spearman's r = 0.47), implying the potential role of TLRs in SLE development. However, mRNA expression of TLR4 and TLR7 was not associated with SLE, clinical indices, or disease severity. CONCLUSIONS: TLR9 is associated with SLE pathogenesis and clinical severity, making it a promising molecule for targeted therapy in SLE management.

Early diagnosis of lupus: A possibilty. A multicentric study from SLE Special Interest Group (SIG) of Indian Rheumatology Association (IRA).

INTRODUCTION: Systemic Lupus Erythematosus (SLE) warrants an early diagnosis and prompt management. Delay in diagnosis can result in repeated flares, permanent damage, and even death. There is a large variability in the time taken to diagnose SLE across the world. We undertook this study to determine the time taken for diagnosis of SLE in India and to identify the factors associated. METHODS: Patients with SLE diagnosed within the previous 1 year as per Systemic Lupus Erythematosus International Collaborating Clinics criteria (SLICC) 2012 criteria were included in a cross-sectional multicentre questionnaire-based survey. Demographic profile, self-reported socioeconomic status as per Kuppuswamy classification of socioeconomic status (version 2022) (SES), and several healthcare related parameters including referral pattern were recorded. Median time taken for diagnosis was used to demarcate early or late diagnosis and associated factors were explored. RESULTS: We included 488 patients with SLE from 10 rheumatology centres. The median time to diagnosis was 6 months Interquartile Range (IQR 3,14.7) and within 3 months in about one third [150(30.7%)]. Very early diagnosis (<1 month) was established in 78(16.0%) patients. The mean SLE Disease Activity Index (SLEDAI) at diagnosis was 10.28+7.24. In univariate analysis, an older age, lower SES, non-southern state of residence and larger family size were significantly associated with late diagnosis. In the multivariate analysis, higher SES (AOR 0.95, 95% CI: 0.92-0.98), multiple organ system involvement at initial presentation (AOR1.75 95%CI: 1.08-2.84) and place of residence in south Indian states (AOR1.92 95%CI: 1.24-2.97) had lesser odds of being associated with late diagnosis. Distance from the closest medical centre/professional did not influence the time to diagnosis. Majority of patients had first consulted a medical graduate (42.5%) or postgraduate doctor (48.2%), and referral to rheumatologist was largely done by postgraduate (65%) doctors. More than half of our patients (61%) self-finance their treatment. CONCLUSION: Median time to diagnosis of SLE was 6 months, 1/3rd being diagnosed within 3 months and 78(16.0%) with 1 month of symptom onset. Delay in diagnosis was noted in those belonging to lower socioeconomic strata and those with single organ disease. Distance to the health care facility did not influence time to diagnosis.

A Rare Case of Concurrent Lupus Mastitis and Sarcoidosis in a 62-Year-Old Female.

Systemic lupus erythematosus (SLE) and sarcoidosis are two of the most well-recognized, chronically diagnosed conditions in the United States, with a plethora of known multisystem manifestations. With regard to breast pathology, lupus mastitis is a relatively uncommon manifestation of SLE, commonly involving both the mammary gland and subcutaneous soft tissues of the breast. Sarcoidosis in the breast is a similarly, exceedingly rare manifestation of this multi-system disorder, classically presenting with non-caseating granulomas. Both present with non-specific mammographic and sonographic features. We present a 62-year-old female with known diagnosis of discoid lupus and Graves' disease who presented initially with an abnormal screening mammogram, ultimately undergoing mammographic work-up and subsequent biopsy demonstrating lupus mastitis, including vasculitis, panniculitis, and fibrosis with chronic inflammation. The patient was also found to have small non-caseating granulomas, some in a perivascular distribution, classically seen in sarcoidosis. Given the rarity of both manifestations, our case explores the coexistence of these autoimmune processes and this atypical presentation.

Demethylzeylasteral ameliorates podocyte damage in murine lupus by inhibiting inflammation and enhancing autophagy.

BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with multiorgan and tissue involvement. Lupus nephritis (LN), an inflammatory condition of the kidneys associated with SLE, represents a significant cause of morbidity and mortality in SLE patients. Current immunosuppressive therapies for LN have limited efficacy and can lead to significant side effects. Demethylzeylasteral (DML) has shown promise in the treatment of LN, but its precise mechanism of action remains unclear. PURPOSE: To assess the therapeutic effects and potential molecular mechanisms of DML in LN METHODS: The study evaluated the renal protective effects of DML in MRL/lpr mice through assessments of immune complex levels, renal function, and pathological changes. Network pharmacology and transcriptomics approaches were used to elucidate the underlying mechanisms. Molecular docking, biacore assay, monoclonal antibody blocking experiments, and in vitro studies were conducted to verify the mechanisms of action. RESULTS: DML treatment reduced levels of anti-Sm and anti-dsDNA IgG antibodies, as well as serum creatinine and blood urea nitrogen levels. DML also mitigated glomerular damage and fibrosis. Mechanistically, DML alleviated podocyte damage by suppressing inflammation and enhancing autophagy through inhibition of the IL-17A/JAK2-STAT3 pathways. Additionally, DML exhibited high binding affinity with IL17A, JAK2, and STAT3. CONCLUSION: These findings provide strong evidence for the beneficial effects of DML in LN, suggesting its potential as a novel therapeutic strategy for improving renal function in autoimmune kidney diseases.

Lupus-prone NZM2328 mice exhibit enhanced UV-induced myeloid cell recruitment and activation in a type I interferon dependent manner.

Though the exact causes of systemic lupus erythematosus (SLE) remain unknown, exposure to ultraviolet (UV) light is one of the few well-known triggers of cutaneous inflammation in SLE. However, the precise cell types which contribute to the early cutaneous inflammatory response in lupus, and the ways that UV dosing and interferons modulate these findings, have not been thoroughly dissected. Here, we explore these questions using the NZM2328 spontaneous murine model of lupus. In addition, we use iNZM mice, which share the NZM2328 background but harbor a whole-body knockout of the type I interferon (IFN) receptor, and wild-type BALB/c mice. 10-13-week-old female mice of each strain were treated with acute (300 mJ/cm2 x1), chronic (100 mJ/cm2 daily x5 days), or no UVB, and skin was harvested and processed for bulk RNA sequencing and flow cytometry. We identify that inflammatory pathways and gene signatures related to myeloid cells - namely neutrophils and monocyte-derived dendritic cells - are a shared feature of the acute and chronic UVB response in NZM skin greater than iNZM and wild-type skin. We also verify recruitment and activation of these cells by flow cytometry in both acutely and chronically irradiated NZM and WT mice and demonstrate that these processes are dependent on type I IFN signaling. Taken together, these data indicate a skewed IFN-driven inflammatory response to both acute and chronic UVB exposure in lupus-prone skin dominated by myeloid cells, suggesting both the importance of type I IFNs and myeloid cells as therapeutic targets for photosensitive patients and highlighting the risks of even moderate UV exposure in this patient population.

Performance of the Systemic Lupus Erythematosus Risk Probability Index (SLERPI) in a cohort of Colombian population.

OBJECTIVE: To evaluate the performance of the Systemic Lupus Erythematosus Risk Probability Index (SLERPI) in Colombian patients with systemic lupus erythematosus (SLE). METHODS: The Colombian cohort included 435 SLE patients and 430 controls with other autoimmune diseases (ADs). Clinical and serological data were collected, and SLE was indicated by SLERPI scores > 7. The American College of Rheumatology (ACR)-1997, Systemic Lupus International Collaborating Clinics (SLICC)-2012, and European League Against Rheumatism (EULAR)/ACR-2019 criteria were used as reference standards. The impact of overt polyautoimmunity (PolyA) on SLERPI performance was assessed. Additionally, multivariate lineal regression analysis was performed to evaluate the contribution of SLERPI features to the overall SLERPI score. RESULTS: SLE patients had higher SLERPI scores (P < 0.0001), with almost 90% meeting "definite" lupus criteria. Main factors influencing SLERPI included immunological disorder (ß:44.75, P < 0.0001), malar/maculopapular rash (ß:18.43, P < 0.0001), and anti-nuclear antibody positivity (ß:15.65, P < 0.0001). In contrast, subacute cutaneous lupus erythematosus/discoid lupus erythematosus (ß:2.40, P > 0.05) and interstitial lung disease (ß:-21.58, P > 0.05) were not significant factors to the overall SLERPI score. SLERPI demonstrated high sensitivity for SLE, both for the overall SLE group and for those without overt PolyA (95.4% and 94.6%, respectively), but had relatively low specificity (92.8% and 93.7%, respectively). The model showed high sensitivity for hematological lupus (98.8%) and lupus nephritis (96.0%), but low sensitivity for neuropsychiatric lupus (93.2%). Compared to the ACR-1997, SLICC-2012 and EULAR/ACR-2019 criteria, SLERPI yielded the highest sensitivity and lowest specificity. CONCLUSION: SLERPI efficiently identified SLE patients in a Colombian cohort, showing high sensitivity but low specificity. The model effectively distinguishes SLE patients, even in the presence of concurrent overt PolyA. Key Points •SLERPI has a high sensitivity, but low specificity compared to ACR-1997, SLICC-2012 and EULAR/ACR-2019 criteria in the Colombian population. •Within the SLERPI score, immunological disorder, malar/maculopapular rash, and anti-nuclear antibody positivity are the strongest predictors of SLE. •SLERPI model can efficiently distinguish patients with SLE, regardless of concomitant overt PolyA. •SLERPI demonstrates high sensitivity in identifying hematological and nephritic subphenotypes of SLE.

Association of gut commensal translocation with autoantibody production in systemic lupus erythematosus.

OBJECTIVE: Bacterial translocation across the gut barrier has been implicated in the pathogenesis of systemic lupus erythematosus (SLE), though underlying mechanisms remain unclear. This study aimed to investigate the role of translocated bacteria in the context of molecular mimicry by utilizing lupus model mice and blood samples from untreated SLE patients. METHODS: Bacterial translocation was evaluated using nonselective cultured mesenteric lymph nodes (MLNs) from B6SKG mice, a lupus model characterized by impaired TCR signalling and gut dysbiosis. The relationships of detected pathobionts with autoantibody production were examined using in vivo experiments, enzyme-linked immunosorbent assay, immunoblotting, and epitope mapping. RESULTS: Culture-based bacterial profiling in MLNs demonstrated that Lactobacillus murinus was enriched in B6SKG mice with elevated anti-dsDNA IgG levels. Subcutaneous injection of heat-killed L. murinus induced anti-dsDNA IgG production without altering T- or B cell subset composition. Immunoblotting and mass spectrometry analysis identified a peptide ATP-binding cassette (ABC) transporter as a molecular mimicry antigen, with its cross-reactivity in lupus mice confirmed by serological assays and in vivo immunization. The L. murinus ABC transporter exhibited surface epitopes that were cross-reactive with sera from lupus mice and patients. The ABC transporter from R. gnavus, known for its pathogenic role in lupus patients, had a similar epitope sequence to that of the L. murinus ABC transporter and reacted with lupus sera. CONCLUSION: ABC transporters from gut bacteria can serve as cross-reactive antigens that may promote anti-dsDNA antibody production in genetically susceptible mice. These findings underscore the role of commensal-derived molecular mimicry and bacterial translocation in lupus pathogenesis.

Establishing minimal clinically important differences for the quality of life scale QLICD-SLE for patients with systemic lupus erythematosus based on ROC curve.

The minimal clinically important difference (MCID) is an important concept with big appeal in a field struggling to interpret quality of life (QOL) and other patient-reported outcomes (PRO), is also a bridge between statistics and clinical medicine. This study uses the ROC curve to formulate the MCID value of the Quality of Life Instruments for Chronic Diseases of Systemic lupus erythematosus (QLICD-SLE V2.0) scale. Using the representative item "In general, would you say your health is" of the MOS item short form health survey(SF-36) as an anchor, the questionnaire of QLICD-SLE V2.0 and the anchor item were used to investigate the patients on the first day of hospitalization, and the day before the patient was discharged. 279 patients with lupus erythematosus were participated in this longitudinal follow-up study. The ROC curve was constructed by using the classification based on the anchor item as the gold standard and the difference score of the scale as the test variable. The cut-off point corresponding to the maximum value of the Youden index in the ROC curve is taken as the minimum clinical importance difference (MCID) value of the QLICD-SLE (V2.0) scale. The Results showed that the MCID of physical domain, psychological domain, social domain, general module, specific module and QLICD-SLE (V2.0) total scale are 8.3, 2.3, 2.5, 2.7, 9.2 and 3.2, respectively. Area under the ROC curve of QLICD-SLE (V2.0) is 0.898, P (Area = 0.5) < 0.001, the sensitivity is 100%, the specificity is 66.9%. It concluded that if the total scores after treatments changes at least 3.2 points positively, the treatment intervention can be considered as clinically significant. It is more convincing to use the corresponding cut-off point as the MCID for ROC curve method can visualize the sensitivity and specificity.

Case Report: A Case Report on an 18-Year-Old Female with Cerebral Vasculitis in Systemic Lupus Erythematosus (SLE).

Cerebral vasculitis is a rare but severe complication of Systemic Lupus Erythematosus (SLE), presenting significant challenges in management due to its potential for devastating neurological consequences and poor prognosis. We present a case of an 18-year-old female with known SLE who presented with seizures, declining cognitive function, and unresponsiveness. Neurological examination, laboratory investigations, and radiological imaging supported the diagnosis of cerebral vasculitis secondary to SLE. Despite aggressive immunosuppressive therapy, the patient's neurological status continued to deteriorate, leading to respiratory failure and multiorgan dysfunction. Ultimately, the patient succumbed to multiorgan failure attributed to severe CNS vasculitis and its complications. This case underscores the importance of early recognition and aggressive management of cerebral vasculitis in SLE while highlighting the need for further research into more effective therapeutic strategies to improve patient outcomes.

Risk factors and prediction model for osteonecrosis of the femoral head in female systemic lupus erythematosus.

Background: Osteonecrosis of the femoral head (ONFH) is a severe complication of systemic lupus erythematosus (SLE) and occurs more frequently in SLE patients than in other autoimmune diseases, which can influence patients' life quality. The objective of this research was to analyze risk factors for the occurrence of ONFH in female SLE patients, construct and validate a risk nomogram model. Methods: Clinical records of SLE patients who fulfilled the 1997 American College of Rheumatology SLE classification criteria were retrospectively analyzed. The Least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic regression analysis were used to summarize the independent risk factors of ONFH in female SLE patients, which were used to develop a nomogram. The predictive performance of the nomogram was assessed using the receiver characteristic (ROC) curve, calibration curves and decision curve analysis (DCA). Results: 793 female SLE patients were ultimately included in this study, of which 87 patients (10.9%) developed ONFH. Ten independent risk factors including disease duration, respiratory involvement, menstrual abnormalities, Sjögren's syndrome, osteoporosis, anti-RNP, mycophenolate mofetil, cyclophosphamide, biologics, and the largest daily glucocorticoid (GC) were identified to construct the nomogram. The area under the ROC curve of the nomogram model was 0.826 (95% CI: 0.780-0.872) and its calibration for forecasting the occurrence of ONFH was good (χ2 = 5.589, P = 0.693). DCA showed that the use of nomogram prediction model had certain application in clinical practice when the threshold was 0.05 to 0.95. In subgroup analysis, we found that the risk of ONFH was significantly increased in age at SLE onset of ≤ 50 years old, largest daily GC dose of ≥50 mg and the therapy of GC combined with immunosuppressant patients with menstrual abnormalities. Conclusion: Menstrual abnormalities were the first time reported for the risk factors of ONFH in female SLE patients, which remind that clinicians should pay more attention on female SLE patients with menstrual abnormalities and take early interventions to prevent or slow the progression of ONFH. Besides, the nomogram prediction model could provide an insightful and applicable tool for physicians to predict the risk of ONFH.

Characteristics and outcomes of biopsy-proven lupus nephritis in the Eastern Cape province of South Africa.

OBJECTIVE: In Africa, the treatment outcomes of lupus nephritis (LN) are not well known. This is especially true in the current era where contemporary treatment options are more widely available. This retrospective study aimed to measure the outcomes of biopsy-proven LN treated at the Livingstone Tertiary Hospital (LTH) Renal Unit in Gqeberha (formerly Port Elizabeth), South Africa and to identify predictors of a poor outcome. METHODS: A retrospective cohort study of 131 patients with biopsy-proven LN who had a kidney biopsy between 01 January 2012 to 31 December 2021 as identified from the biopsy register. A sub-analysis of 107 patients with proliferative and/or membranous LN was performed. RESULTS: Mean age was 31.4 ± 12.7 years with a female predominance of 86.3%. At 6-month follow-up, 69.6% of patients had complete or partial response to treatment. This increased to 70.3% and 72.6% at 18 and 30 months, respectively. Twenty-seven patients were lost to follow-up, while 7 (5.3%) patients progressed to kidney failure (KF). There were 3 (2.3%) deaths. Predictors of poor response were an elevated baseline serum creatinine (OR = 2.53, 95% CI 0.99 - 6.52, p = .054), a decreased eGFR (OR = 2.92, 95% CI 0.94 - 9.09, p = .065) and an elevated blood pressure (OR = 6.06, 95% CI 1.11 - 33.33, p = .038) at the time of biopsy. Infections were the most common adverse event with 50 infections seen in 39 (29.8%) patients. Herpes viral infections were frequently noted (n = 12) accounting for 24.0% of all documented infections. CONCLUSION: Response rates were similar in this cohort when compared to other contemporary studies. Predictors of poor response were an elevated baseline serum creatinine, a decreased eGFR and an elevated blood pressure at time of the biopsy. Infections were the most common occurring adverse event, although the mortality rate remained low at 2.3%.