Relationship between type 1 diabetes and autoimmune diseases in european populations: A two-sample Mendelian randomization study.

Background: Previous studies have suggested an association between Type 1 diabetes (T1D) and autoimmune diseases (AIDs), but the causal relationship remains unclear. Therefore, this study utilizes publicly available Genome-Wide Association Studies (GWAS) databases and employs a two-sample Mendelian Randomization (MR) approach to explore the causal relationships between T1D and systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and inflammatory bowel disease (IBD). Methods: Summary GWAS data for T1D, SLE, RA, and IBD were downloaded from open GWAS databases and the International Inflammatory Bowel Disease Genetics Consortium (IIBDGC). We employed a series of methods to select instrumental variables closely related to T1D. To enhance the reliability of our conclusions, we applied multiple robust analytical methods, with the inverse variance weighted (IVW) method as the primary approach. Validation and meta-analysis were conducted using the FinnGen consortium. Additionally, we assessed heterogeneity, pleiotropy, and sensitivity to ensure the robustness of our conclusions. Results: A potential causal association was found between T1D and SLE (OR = 1.37, 95% CI = 1.26 - 1.49, P < 0.001), which was further confirmed by meta-analysis. Similarly, a potential causal association was found between T1D and RA (OR = 1.32, 95% CI = 1.17 - 1.50, P < 0.001), and this was also confirmed by meta-analysis. Although the association between T1D and IBD showed P < 0.05, the leave-one-out test did not pass, and further meta-analysis indicated no significant statistical association between them. Conclusion: Our study reveals the relationships between T1D and three clinically common autoimmune diseases (SLE, RA, and IBD). This research supplements previous studies and provides a reference for future clinical work.

Role of Interleukin-17 in Predicting Activity of Rheumatoid Arthritis and Systemic Lupus Erythematosus.

Background: Although high serum levels of interleukin (IL)-17 and its producing cells have been found in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) in earlier research, it is still unclear how these findings relate to disease activity. Objectives: This study examines the link between serum levels of IL-17 and the activity of both RA and SLE. Design: This pilot case-control study included 100 patients with RA, 100 with SLE, and 100 healthy controls. Methods: The Disease Activity Score-28 (DAS28) scores assessed the activity of RA, whereas the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) scores assessed SLE activity. All participants' data were compared and correlated. Results: Serum levels of IL-17 were significantly higher in RA and SLE patients compared with the controls (P < .001) and showed significantly positive correlations (P < .001) with rheumatoid factor titer, anti-cyclic citrullinated peptide (anti-CCP) and DAS28 score among the RA patients. Although among SLE patients, they were significantly positively correlated (P < .001) with anti-double-stranded DNA (anti-ds DNA) levels and the SLEDAI-2K scores, the best cut-off value of IL-17 for predicting moderate and high disease activity was > 175 pg/mL among RA patients and > 95 pg/mL among SLE patients. Conclusions: There is a significant correlation between RA and SLE activity and serum levels of IL-17. This discovery emphasizes IL-17 as a potential therapeutic target.

Impact of connective tissue diseases on complications following aesthetic surgery: A matched cohort study.

BACKGROUND: The association between connective tissue diseases (CTDs), including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and scleroderma, and complications following aesthetic surgery is under-investigated. We hypothesized that the risk of complications following aesthetic surgery was higher in patients with these connective tissue disorders compared to matched non-CTD patients. METHODS: All patients diagnosed with RA, SLE, and scleroderma who underwent aesthetic surgery at our institution from 2003-2022 were reviewed. Demographic data, comorbidities, medications, procedures, and postoperative complications were collected. Non-CTD controls were identified for each procedure and matched 1:1 based on propensity scores derived from race, sex, body mass index, smoking status, and comorbidities. RESULTS: Six hundred 38 patients were included, comprising 319 (50%) patients diagnosed with CTD and 319 (50%) controls. The average age at surgery was 56.3 years. There were 129 complications. There were no differences between the CTD and non-CTD patients in number of total complications (69 versus 60, p = 0.38), major complications (23 versus 16, p = 0.25), or minor complications (46 versus 44, p = 0.73). Complications were not significantly different between CTD patients and controls who underwent blepharoplasty (p = 0.38), breast reduction (p = 0.91), abdominoplasty (p = 0.46), or rhytidectomy (p = 0.50). CTD patients who underwent breast augmentation had significantly more complications than matched non-CTD patients in bivariate analysis (7 versus 0, p = 0.018*) and multivariable logistic regression (OR: 10.2, 95% CI: 1.21 to 93.3, p = 0.039*). CONCLUSIONS: Most aesthetic surgeries can safely be performed in patients with CTDs. Patients seeking breast augmentation should be counseled on a potentially increased risk of postoperative complications.

Improved diagnosis of systemic lupus erythematosus with human-derived double-stranded DNA antigen.

Anti-double-stranded DNA antibodies (anti-dsDNA) serve as a crucial serological indicator for systemic lupus erythematosus (SLE). Chemiluminescent immunoassay (CIA) is mainly used in clinical diagnosis of SLE, but suffers from low specificity, partially because the use of dsDNA antigens of varied sources in current CIA kits that sometimes led to controversial results. On the basis that anti-dsDNA in healthy individuals tend to selectively bind with dsDNA originating from pathogens, whereas pathogenic anti-dsDNA in SLE patients bind all forms of dsDNA, here we proposed the use of dsDNA fragment derived from human genome as antigen (synthesized via PCR using the human genomic DNA as the template). A magnetic bead-based immunofluorescence assay (IFA) was thus developed for SLE diagnosis, which exhibited improved sensitivity and specificity over CIA using the WHO reference reagent (15/174) as standard. For clinical serum sample analysis (n = 590), IFA exhibited an accuracy of 71.9% that was higher than CIA (65.3%). Crucially, the IFA results exhibited stronger correlations with the activity of SLE, renal involvement, and its prognosis. Besides the improved clinical diagnosis, the proposed IFA also holds great promise in assay standardization due to the high homogeneity of the synthetic dsDNA.

Blood-dominant disease in late-and-early-onset lupus: A systematic review and meta-analysis.

OBJECTIVES: Numerous studies have explored hematological manifestations in early-onset systemic lupus erythematosus (erSLE) (age ≤ 50) and late-onset SLE (ltSLE) patients (age > 50), yielding diverse results. This study employs a meta-analysis to examine differences in hematologic manifestations between ltSLE and erSLE. METHODS: Studies investigating the frequency of hematological manifestations in ltSLE patients were included. The frequencies of autoimmune hemolytic anemia (AIHA), thrombocytopenia (TP), lymphopenia, leukopenia, lymphadenopathy, and thrombosis were compared between erSLE and ltSLE groups. Two authors independently reviewed and assessed data consistency among abstracts, tables, and text to mitigate bias. Forest plots were utilized to compare odds ratios (95 % CI) of hematological manifestations by age groups, and study heterogeneity was evaluated using I2. RESULTS: The analysis included 39 eligible studies with 19,103 SLE patients (16,314 erSLE, 2789 ltSLE). Among these studies, 28 reported AIHA which was found to be more frequent in erSLE (OR = 1.29, 95 %CI = 1.11-1.39, p = 0.0008). Twenty studies provided data on lymphopenia which was found to be more frequent in erSLE (OR = 1.184, 95 %CI = 1.063-1.318, p = 0.0021). 32 studies included data on leukopenia and the frequency was higher in erSLE (OR: 1.338, 95 %CI: 1.22-1.47, p < 0.0001). Lymphadenopathy was more prevalent in erSLE (OR = 2.32, 95 % CI = 1.61-3.34, p < 0.0001). No significant difference was observed in thrombosis and TP frequency between the two groups. CONCLUSION: Attributing hematological findings to SLE in late-onset patients presents challenges due to comorbidities and polypharmacy. Overall, the frequencies of AIHA, lymphopenia, leukopenia, and lymphadenopathy were more common in erSLE patients compared to ltSLE in this study.

Does the standard proteinuria cut-off for renal biopsy in lupus nephritis as per the current guidelines hold good for Asian population? A single-centre study from South India.

INTRODUCTION: Current rheumatology and nephrology society guidelines in lupus nephritis do not recommend renal biopsy for proteinuria of less than 500 mg/24 h. This might lead to a significant delay in the early diagnosis of lupus nephritis. AIM: The main aim of this study is to determine the nature of renal lesions in patients with low-grade proteinuria and to analyze the predictors for clinically significant lupus nephritis. METHODS: This was a single-center, retrospective study. All consecutive patients of lupus nephritis, with low-grade proteinuria (200 mg to 500 mg/24 h) undergoing renal biopsy were enrolled in this study. The renal biopsies were classified into significant lesions (Class III/IV/V) and non-significant lesions (Class I and II). Treatment naïve groups and treatment-modified groups were analyzed separately. Predictive factors for significant renal lesions were determined by univariate and multivariate analysis. RESULTS: We identified 183 patients of lupus with proteinuria between 200 and 500 mg / 24 h. Mean (SD) age was 30.2 (11.39) years with 167 (91.2%) of them being females. The mean (SD) baseline proteinuria was 351.03 (98.1) mg/24 h 85 patients (46.5%) had proliferative lupus nephritis where whereas 17 patients (9.3%) had membranous nephropathy. Crescents and fibrinoid necrosis were seen in 10 (5.46%) and 24 (13.11 %) patients respectively. Isolated proteinuria without any other sediments was seen in 95 patients (51.9%) of which 29 patients had proliferative lupus nephritis. Elevated Anti-double stranded DNA (anti-dsDNA), low C3, low C4 and the presence of urinary sediments were significantly associated with significant renal lesions in biopsy. CONCLUSION: Significant renal lesions were seen in around half of the patients with low-grade proteinuria underscoring the importance of performing a renal biopsy in this set of patients. Low C3 and C4, urinary sediments, and elevated anti-dsDNA were predictors for significant renal lesions.

Elucidating the mechanisms and efficacy of antimalarial drugs in Systemic lupus erythematosus.

INTRODUCTION: Antimalarials (AMs) are old drugs with a wide range of beneficial effects in systemic lupus erythematosus (SLE) beyond the control of lupus activity, including protection against damage accrual and improved survival. Nowadays, hydroxychloroquine (HCQ) is considered the background therapy for every patient with SLE. Despite this well-proven long-term efficacy, the most recent debate is focused on defining the optimal doses to assure the best benefit/risk ratio. AREAS COVERED: We have reviewed the pharmacological basis underlying the various therapeutic effects of AMs, with special attention put on the pharmacokinetics, in order to better understand the conflicting results regarding HCQ dosing. Also, we have updated the beneficial and toxic effects of HCQ and also discussed the role of mepacrine not only as a substitute in cases of maculopathy, but also as a very effective therapy combined with HCQ. We searched PubMed and Embase for articles published in English at any time. We used the terms 'hydroxychloroquine' or 'mepacrine' or 'chloroquine' or 'antimalarials,' 'pharmacokinetics,' 'efficacy,' 'remission,' 'toxicity,' 'adherence.' We reviewed full-text articles, including original research articles, large observational studies, systematic reviews, and expert consensus statements. Additionally, studies were identified through the assessment of the reference lists of the evaluated manuscripts. EXPERT OPINION: We advocate for the widespread use of HCQ at stable doses of 200 mg/d, which are below 4 mg/kg/d for most patients, and also for the early combination therapy with mepacrine, used as an add-on drug, to assure a good control of SLE activity, and also a durable and safe use of these essential drugs for the management of SLE.

Longitudinally Extensive Transverse Myelitis in a Patient With Systemic Lupus Erythematosus: A Case Report and Literature Review.

Longitudinally extensive transverse myelitis (LETM) is a rare but severe neurological complication of systemic lupus erythematosus (SLE). The existing literature contains only limited information about this condition. We present a case of a 38-year-old female with SLE who presented with quadriparesis. Magnetic resonance imaging (MRI) of the brain and spinal cord showed T2-weighted high signal intensity involving the brainstem, bilateral middle and inferior cerebellar peduncles, and C1-C7 spinal cord segments. Early intervention with high-dose methylprednisolone and cyclophosphamide was initiated, resulting in partial clinical recovery. A comprehensive literature review highlights the importance of early diagnosis and treatment, discusses the potential etiologies, and explores the prognostic factors influencing patient outcomes. This case report underscores the need for a high level of clinical suspicion and prompt therapeutic intervention to improve prognosis in SLE patients presenting with LETM.

Early human migration determines the risk of being attacked by wolves: ethnic gene diversity on the development of systemic lupus erythematosus.

The prevalence of systemic lupus erythematosus (SLE) varies significantly based on ethnicity rather than geographic distribution; thus, the prevalence is higher in Asian, Hispanic, and Black African populations than in European populations. The risk of developing lupus nephritis (LN) is the highest among Asian populations. Therefore, we hypothesize that human genetic diversity between races has occurred through the early human migration and human genetic adaptation to various environments, with a particular focus on pathogens. Additionally, we compile the currently available evidence on the ethnic gene diversity of SLE and how it relates to disease severity. The human leukocyte antigen (HLA) locus is well established as associated with susceptibility to SLE; specific allele distributions have been observed across diverse populations. Notably, specific amino acid residues within these HLA loci demonstrate significant associations with SLE risk. The non-HLA genetic loci associated with SLE risk also varies across diverse ancestries, implicating distinct immunological pathways, such as the type-I interferon and janus kinase-signal transducers and activators of transcription (JAK-STAT) pathways in Asians, the type-II interferon signaling pathway in Europeans, and B cell activation pathway in Africans. Furthermore, assessing individual genetic susceptibility using genetic risk scores (GRS) for SLE helps to reveal the diverse prevalence, age of onset, and clinical phenotypes across different ethnicities. A higher GRS increases the risk of LN and the severity of SLE. Therefore, understanding ethnic gene diversity is crucial for elucidating disease mechanisms and SLE severity, which could enable the development of novel drugs specific to each race.