Lupus最新文献

ObjectiveLupus nephritis (LN) is a major mortality risk factor in patients with systemic lupus erythematosus (SLE). We investigated the predictors of end-stage renal disease (ESRD) and mortality in patients with LN.MethodsWe enrolled 599 Korean patients with biopsy-proven proliferative or membranous LN from a prospective cohort of 1497 patients with SLE. Baseline demographics, serology, histology, disease activity, and organ damage were collected and assessed. Regression models were used to evaluate predictors of renal survival and mortality.ResultsWe followed a total of 599 patients with proliferative LN (class III or IV/±V, N = 509) or membranous LN (class V, N = 90). Among these patients, 42 patients (7.0%) progressed to ESRD and 31 (5.2%) died. In a multivariate logistic regression analysis, antiphospholipid antibody positivity (OR 3.18, p = .023), higher activity and chronicity indices at biopsy (OR 1.14, p = .034; OR 1.33, p = .042), and sustained high disease activity (extra-renal adjusted mean Systemic Lupus Erythematosus Disease Activity Index-2000 [SLEDAI-2K] ≥ 3, OR 4.33, p = .019) significantly influenced progression to ESRD after adjusting for age at LN diagnosis, gender, disease duration, and hypertension. While the 6-month renal response after induction treatment showed no association with ESRD risk, the 12-month treatment response demonstrated a significant association (p < .001). Renal survival was poorer in patients with an activity index ≥6 and in those with a chronicity index ≥4 (p = .013 and p = .002, respectively). Patients who developed ESRD had significantly worse overall survival than those who did not (p = .028). Higher adjusted mean SLEDAI-2K (hazard ratio [HR] 1.43, p < .0001) and higher extra-renal adjusted mean SLEDAI-2K (HR 1.83, p < .0001) were significantly associated with increased overall mortality.ConclusionsOur study indicates that antiphospholipid antibodies, higher histologic activity and chronicity indices, and sustained high disease activity beyond renal items were independently associated with progression to ESRD. Mortality was increased among patients with ESRD and those with persistent high disease activity. These findings emphasize the need for stringent disease activity control and support clinicopathologic stratification to identify patients at high risk of adverse long-term renal outcomes.

IntroductionWhile Systemic Lupus Erythematosus (SLE) typically presents with a multifactorial etiology, rare monogenic forms exist, usually diagnosed during childhood with a severe clinical course. This study aims to identify monogenic causes of SLE within the pediatric population of Northern Israel and to suggest criteria for genetic evaluation in patients with childhood-onset SLE.MethodsClinical and genetic data were collected from a single tertiary pediatric medical center in Israel, between 2010 and 2021. Patients diagnosed with SLE before the age of 18 years were enrolled in the study. Monogenic SLE was suspected in patients with any of the following criteria: (1) family history of SLE, (2) consanguinity, (3) early onset of symptoms (under 10 years), (4), atypical clinical course, (5) male gender, (6) syndromic features. Genetic evaluations were performed for these patients.ResultsSeventy-five patients were diagnosed with SLE, of whom 18 (24%) met the criteria for suspected monogenic SLE. Genetic evaluations were conducted for 13 out of the 18 patients (72%) leading to a diagnosis of a monogenic form of SLE in 6 of the 13 patients (46%), and total of 8% from the entire cohort. Four patients were diagnosed with prolidase deficiency, one patient with Aicardi-Goutières syndrome (AGS) and one patient with Spondyloenchondrodysplasia with immune dysregulation (SPENCDI) syndrome. Additionally, candidate variants in C4B and ITPR3 genes were detected in an additional pedigree.ConclusionsMonogenic SLE was identified in 46% of the children within this selected cohort. A genetic diagnosis can yield direct clinical implications and enhance our understanding of the mechanisms involved in the more common sporadic forms of SLE.

BackgroundSystemic lupus erythematosus (SLE) is an autoimmune disease with frequent renal involvement. Although current remission induction therapies are effective, a high proportion of patients experience flares or are treatment-resistant. Combining immunosuppressants with Calcineurin Inhibitors (CNIs) may improve clinical response, but insufficient data exist for the Hispanic population.MethodsPatients with SLE and lupus nephritis (LN) with persistent proteinuria despite previous immunosuppression and who began a combined regimen, including CNIs, were included. 24-hour proteinuria and glomerular filtration rate (eGFR) as estimated by CKD-EPI were evaluated at 12 months and stratified by LN histological class.Results239 clinical records from patients with LN diagnosis were evaluated, and 42 met the inclusion criteria. At 12 months, complete and partial responses were reached by 26.2% and 35.7% of patients, respectively. Compared with baseline, a significant reduction in proteinuria was observed (2.89 vs 0.72 g/d, p < .001), and a transient decrease in eGFR was detected at 6 months (109 vs 104 mL/min/1.73 m², p = .001), which improved significantly at 12 months (109 vs 114 mL/min/1.73 m², p = .023).ConclusionFor a Mexican cohort of patients with treatment-resistant lupus nephritis, the addition of CNIs can be effective. It achieves excellent biochemical response rates despite a transient reduction in eGFR that improves without treatment withdrawal.

IntroductionCutaneous lupus can manifest with acute, subacute, and chronic eruptions triggered and exacerbated by ultraviolet exposure, making photoprotection an evidence-based aspect of disease management. This study aims to assess skincare and photoprotection knowledge and habits, medical information sources, and accessibility barriers among patients with lupus to identify knowledge gaps and inform educational initiatives.MethodsA cross-sectional 41-question survey was distributed via REDCap to adult participants with self-reported lupus identified through Research Match, the Northwestern Medicine Enterprise Data Warehouse, and lupus community organizations from August 2022 to March 2023. Data analysis was conducted in R version 4.3.1, and descriptive and linear regression model tests were performed.ResultsOf 129 initiated questionnaires, 115 were completed and met eligibility criteria. Only 43% correctly identified UVA protection on sunscreen labels, and 49% reported daily sunscreen use. Most participants reported receiving skincare information from dermatologists (49%) or rheumatologists (40%), with no statistically significant differences in knowledge level between groups (p = 0.38). Participants with Fitzpatrick skin tones III-IV and V-VI had significantly lower photoprotection knowledge scores compared to Fitzpatrick skin tones I-II (p = 0.002 and p = 0.0006, respectively). Participants with lower incomes (≤$75,000) scored lower than those with higher incomes (>$75,000; p = 0.003). One-third (33%) endorsed difficulty affording the management of their lupus and 15% reported that the cost of sunscreen influenced sunscreen use.ConclusionsThese exploratory findings highlight a need for targeted educational efforts to improve lupus management and outcomes, particularly in low-income groups and communities of color. Dermatologists and rheumatologists care for a substantial portion of patients with lupus and share a responsibility to educate and address these gaps.

BackgroundSystemic Lupus Erythematosus (SLE) is a multisystemic autoimmune disease involving Interleukin-23 (IL-23), a pro-inflammatory cytokine that promotes Th17 cell differentiation, contributing to SLE pathogenesis. However, studies assessing IL-23 levels in SLE patients have reported inconsistent findings. This meta-analysis aimed to evaluate the association of circulating IL-23 levels with SLE, including their correlation with disease activity.Materials and MethodsFive databases (PubMed, Scopus, ScienceDirect, Web of Science, and EBSCOhost) were utilized for a systematic search of observational studies comparing IL-23 levels in SLE patients and healthy controls, along with the SLE Disease Activity Index (SLEDAI), to assess disease activity. The Newcastle-Ottawa Scale (NOS) was used for the data extraction process and quality assessment. Comprehensive Meta-Analysis (CMA) v4 was used as another tool to perform the meta-analysis. Moreover, robustness of findings was assured by Trial Sequential Analysis (TSA), sensitivity analysis, heterogeneity, and publication bias.ResultsResults were derived from 12 studies involving 680 SLE patients and 416 healthy controls. Elevated levels of IL-23 were reported in SLE patients compared to controls (MD = 71.467; 95% CI: 26.44-116.49; p = 0.002) in the pooled analysis. IL-23 levels were higher in active versus inactive SLE (MD = 27.777; p = 0.085), although the difference was statistically insignificant. A significant positive correlation was recorded between IL-23 and SLEDAI scores (correlation coefficient = 0.510; p = 0.027). Ethnicity-specific analysis supported similar trends in East Asian and Middle Eastern populations. Sensitivity and TSA confirmed the robustness and adequacy of the sample size for the association between IL-23 and SLE.ConclusionThis meta-analysis reveals a significant association between elevated IL-23 levels and SLE, suggesting its potential as a diagnostic and prognostic biomarker. Further longitudinal studies are required to validate its utility in SLE monitoring and therapy.

BackgroundOrbital myositis (OM) is an uncommon ocular manifestation of systemic lupus erythematosus (SLE) and is typically characterized by acute painful proptosis and diplopia. Only isolated painful cases have been documented, and these usually occur without systemic activity.CaseA 44-year-old woman with a six-year history of SLE developed painless bilateral proptosis and mild abduction restriction during a severe multisystem flare involving the kidneys, lungs, and gallbladder. Laboratory studies revealed high anti-dsDNA titres, hypocomplementemia, and elevated inflammatory markers. Orbital computed tomography demonstrated isolated enlargement of both lateral rectus muscles without evidence of infection, sinus disease, or thyroid orbitopathy. She received intravenous methylprednisolone 1000 mg daily for 3 days, followed by an oral prednisone taper (1 mg/kg/day) and intravenous cyclophosphamide 1000 mg every 4 weeks for six pulses. Both ocular and systemic manifestations resolved within 24 hours of initiating pulse therapy. During admission, she developed acalculous cholecystitis, attributed to active lupus vasculitis after multidisciplinary assessment.ConclusionThis represents the first reported case of painless orbital myositis associated with systemic lupus erythematosus during a multi-systemic flare. Rapid response to corticosteroid and cyclophosphamide therapy underscores the inflammatory, reversible nature of this manifestation. Recognition of OM as a potential lupus complication is critical for prompt diagnosis, exclusion of infectious causes, and early initiation of aggressive immunosuppression to preserve vision and prevent systemic morbidity.

ObjectiveThe purpose of this systematic review study was to showcase diagnostic challenges posed by lupus mastitis (LM).MethodsHere we report a case of a 47-year- old Caucasian female with LM heralding systemic lupus erythematosus (SLE) complicated by macrophage activation syndrome (MAS), in the light of a systematic review of the literature on LM.ResultsIncluding our patient, we identified 32 case reports of patients with LM in the course of SLE. Only in 6 cases, including ours, LM preceded SLE diagnosis. Ours is the first ever published case report of LM heralding MAS.ConclusionLM in the course of SLE is rare and published data is very limited. Diagnosis should be made combining physical exam, laboratory tests, imaging and histology results, and include differentiation from other autoimmune, malignant and infectious causes. Based on the reviewed literature, it is advised to consider minimally invasive core biopsies in lupus patients over open biopsies as the associated trauma may exacerbate local inflammation. Conservative treatment with immunosupressive and anti-inflammatory drugs allows for control of breast symptoms in most cases.

BackgroundRecently, Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) gene has emerged as an attractive candidate gene implicated in susceptibility to autoimmune disease such as Juvenile-onset SLE (JSLE).ObjectiveTo investigate CTLA-4 exon 1 + 49A/G (rs231775) SNP as a genetic marker for susceptibility to JSLE and lupus nephritis in Egyptian children and adolescents.MethodsThis prospective case-control study included 260 patients diagnosed with Juvenile-onset SLE, and 260 healthy controls. We genotyped all participants for CTLA-4 (A/G) (rs231775) SNP located in exon 1 at position 49 by polymerase chain reaction.ResultsThe CTLA-4 exon 1 + 49G/G gene variant and G allele were significantly more represented in JSLE patients than healthy controls (27% vs 8%; ORs = 4.2; [95% CI: 2.4 - 7.3]; for the G/G genotype) and (47.5% vs 35%; ORs: 1.7; [95% CIs: 1.3 - 2.2]; for G allele); P < .01. The CTLA-4 G/G genotype and G allele were identified as possible risk factors for development of lupus nephritis (for G/G genotype; ORs: 5.09; [95% CIs: 1.7 - 13.9]; P = .0001, and for G-allele; ORs: 2.4; [95% CIs: 1.5 - 3.78]; P = .004).ConclusionThe CTLA-4 exon 1 + 49A/G polymorphism may confer susceptibility to Juvenile-onset SLE. Moreover, CTLA-4 G/G genotype and G allele at exon 1 + 49 may constitute independent risk factors for development of lupus nephritis in Egyptian children and adolescents.

BackgroundSystemic lupus erythematosus (SLE) is a multisystem autoimmune disease characterized by the production of various antibodies and immune complex-mediated injury. Limited information exists about Kazakh patients, a heterogeneous group with different clinical manifestations and potentially unique genetic basis.ObjectiveTo describe the clinical features, associated autoantibody and cytokine profile, and the frequency of rare variants in a limited panel of genes.MethodThis study enrolled 43 Kazakh individuals: 25 with SLE and 18 healthy controls. Disease activity was assessed using the SLEDAI-2K score. Laboratory tests included C3 and C4 complement components, interleukin (IL)-6, IL-5, IL-10, IL-18, IFN and antiphospholipid IgG/IgM identified by ELISA. The antinuclear factor (ANF) on HEp-2 cells was detected using indirect immunofluorescence. Specific autoantibodies were identified by immunoblotting. A custom AmpliSeq panel of 120 genes was used on the Ion Proton Sequencer.ResultsSLE patients (SLEDAI-2K = 11,48 ± 8,7) demonstrated skin lesions (88%), joint involvement (84%), lupus nephritis (56%), and hematological disorders (40% patients). Cardiac and vascular injury was each observed in 36% of patients, while involvement of nervous system, mucous membranes, and thyroid gland each occurred in 8% of cases. Immunological tests revealed positive ANF in the majority of patients (92%) with anti-dsDNA, nucleosomes, Smith, SS-A/Ro52, SS-A/Ro60, U1-snRNP, and Rib-P0 antibodies. IL-6, IL-18, IFN levels were markedly elevated in patients with SLE relative to controls (p = .02), reflecting enhanced systemic inflammatory activity. Elevated IL-10 was found as well in patients with SLE relative to controls (p = .02). According to the results of gene panel sequencing, the most significant variants were found in genes SAMD9L, REL, IRAK1, PTPRC, TLR7, TNFAIP3, IL6ST, BLK, CCR5, TFPI, CLEC16 A, IL2RB, ITGA2B, ABCC2, KIF5A, NCF2, and CD5, none of which showed statistically important enrichment in the disease cohort.ConclusionAnalysis of data obtained from Kazakh patients with SLE revealed diverse autoimmune profiles, including various antibodies, pro- and anti-inflammatory cytokines, as well as several variants in REL, IRAK1, PTRPC, IL6ST genes. The findings presented may contribute to the development of personalized diagnostic tools for predicting disease trajectories and guiding treatment decisions.

Background: Anti-phospholipid syndrome (APS) is systemic autoimmune disorder defined as presence of anti-phospholipid antibodies with multiple obstetric complications. miR-146a-5P and miR-155-5P regulate APS and its associated inflammatory cytokines. Purpose: Our aim is to study expression levels of miR-146a-5p, miR-155-5p and pro-inflammatory cytokine interleukin-8 (IL-8) among pregnant females having APS. Research design: It is a case-control study. Data Collection and Analysis: Case group consisted of 50 pregnant women having APS. Control group consisted of 50 healthy pregnant women. Expression levels of miR-146a-5p and miR-155-5p were determined by quantitative reverse transcription polymerase chain reaction method (qPCR). IL-8 levels were determined using enzyme-linked immunosorbent assay (ELISA). Results: miR-146a-5p (mean ± SD), p value (confidence interval (CI)) among APS group versus Control group = (0.95 ± 0.7) versus (0.27 ± 0.4); 0.01 (0.44-0.90). miR-146a-5p had area under curve (AUC) of 0.813, sensitivity 66% & specificity 86%. miR-155-5p (mean ± SD); p value (CI) among APS group versus Control group = (0.57 ± 1.0) versus (0.48 ± 0.7); 0.60 (-0.25-0.43). miR-155-5p had (AUC) of 0.582, sensitivity 92% & specificity 40%. (mean ± SD); P value (CI) of IL-8 in APS group versus control group = (6.11 ± 1.2) versus (5.19 ± 0.5); CI(-0.36- 0.52), p < .001. Conclusion: miR-146a-5p significantly higher among APS group. IL-8 significantly more predominates among APS group. Alterations in miRNA expression are involved in thrombosis associated pregnancy complications.