Deoxyribonucleic Acid Antibodies Research Articles

CX-5461 ameliorates disease in lupus-prone mice by triggering B-cell ferroptosis via p53-SLC7A11-ALOX12 pathway

CX-5461, a first-in-class compound, is widely recognized as a selective inhibitor of RNA polymerase I. Recently, it has been reported to possess novel immunosuppressive properties with significant therapeutic effects in transplantation immune rejection. However, the potential use of CX-5461 for Systemic Lupus Erythematosus (SLE) treatment remains unknown. In this study, we elucidated the mechanism underlying the therapeutic efficacy of CX-5461 in lupus. Our findings demonstrated that CX-5461 selectively targets B cells and effectively reduces the proportions of B cells, germinal center B cells, and plasma cells in MRL/MPJ-Faslpr and Resiquimod (R848)-induced lupus mice. Molecular studies revealed that CX-5461 modulates CD36-Acyl-CoA Synthetase Long Chain Family Member 4 (ACSL4)-mediated glycerolipid metabolism in B cells, triggering ferroptosis through the p53- Solute Carrier Family 7 Member 11 (SLC7A11)- Arachidonate 12-Lipoxygenase (ALOX12) pathway, thereby decreasing IgG and Anti-Double-Stranded Deoxyribonucleic Acid (dsDNA) antibody levels and attenuating lupus. Collectively, these results suggest that CX-5461 holds promise as an effective candidate for targeted therapy against lupus.

Clinical and laboratory profiles of systemic lupus erythematosus patients in a new rheumatology clinic in southwestern Nigeria.

The aims were to study the sociodemographic characteristics of patients presenting to the clinic and to study the clinical and serological pattern of systemic lupus erythematosus (SLE) in a new rheumatology clinic of a predominantly Yoruba population. This was a retrospective, cross-sectional study conducted over 7 years (January 2017 - December 2023). Patients who satisfied the 1997 American College of Rheumatology (ACR) and/or the 2012 Systemic Lupus International Collaborating Clinics (SLICC) classification criteria were enrolled using their medical records. Patients with overlap syndromes and other inflammatory or noninflammatory rheumatic diseases were excluded from the study. Their sociodemographic, clinical, laboratory, and treatment data were retrieved from their medical records and analysed using IBM SPSS version 23.0 software. A total of 65 patients were diagnosed with SLE with a frequency of 15.8%. The mean age ±SD of the patients at presentation was 33.85 years ±11.01 and the female to male ratio was 9.8 : 1. The median (IQR) duration of symptoms at presentation was 7.0 months (3-24). The common clinical presentations included synovitis (86.2%), acute cutaneous rash (53.8%), oral ulcers (52.3%), nonscarring alopecia (50.8%), and serositis (47.7%). Proteinuria was seen in 37.7% of the patients and the predominant renal histopathological feature was Class IV. Antinuclear antibody was 100% positive with 50.94% of the patients having a titre of 1 : 5,120 and above. Anti-double-stranded deoxyribonucleic acid and anti-Smith antibodies each had 50% prevalence. Dyslipidaemia was found in 76.7% of the patients. The study's findings are largely consistent with similar studies done in Africa. Further prospective multi-centred studies are needed to further determine the epidemiological characteristics of the disease in Nigeria with a multi-ethnic population.

Cardiovascular Morbidity in Systemic Lupus Erythematosus: A Single-Center Retrospective Study.

Systemic Lupus Erythematosus (SLE) is an autoimmune inflammatory condition affecting multiple systems. Cardiovascular morbidity is a significant concern, with around 25% of SLE patients experiencing cardiac complications. This study aims to determine the prevalence of cardiovascular morbidity in SLE patients in King Fahad Medical City (KFMC) in Riyadh, Saudi Arabia. This retrospective record-based research was conducted at KFMC from January 2015 to October 2023. A review of the medical files of all SLE patients was accomplished. The vast majority of the patients (90.9%) were females. The mean age for the patients was 36.5 years. The most common comorbidities were lupus nephritis (34.6%), hypothyroidism (18.4%), and anti-phospholipid syndrome (9.2%). The most commonly used medications were hydroxychloroquine (81.8%), corticosteroids (prednisolone) (43.0%), and mycophenolate mofetil (27.9%). Around 45.2% (n= 176) of the patients with SLE developed cardiovascular complications. The most commonly reported cardiovascular diseases that developed after diagnosing patients with SLE were hypertension (22.4%), valvular heart diseases (13.2%), and dyslipidemia (9.2%). The study also found that anti-dsDNA antibodies can reduce the likelihood of developing hypertension by 40%. This research contributes to the medical literature on SLE and sets the stage for future research on personalized healthcare strategies for managing SLE and its complications. This study highlights that a considerable proportion of SLE patients(~50%) develop cardiovascular complications, with hypertension, valvular heart diseases, and dyslipidemia being the most common. We also discovered that anti-double-stranded deoxyribonucleic acid antibodies (Anti-dsDNA) reduce the likelihood of developing hypertension.

JACCOUD’S ARTHROPATHY IN SYSTEMIC LUPUS ERYTHEMATOSIS: A CASE REPORT

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease with a wide range of clinical signs and symptoms. Musculoskeletal problems (e.g. arthralgia, inflammatory arthritis, and non-erosive arthritis) are the first symptom in roughly 80% of individuals. Jaccoud’s arthropathy, which is regarded as reversible, non-erosive, and deforming arthropathy, can be observed in patients with systemic lupus erythematosus in relation to tenosynovitis, capsule retraction, ligament laxity, and muscular imbalance. Risk factors include longer disease duration, higher titers of rheumatoid factor, and anti–double stranded deoxyribonucleic acid (anti-dsDNA) antibody positivity. In the current article, a case with SLE and associated Jaccoud’s arthropathy was presented.

Neuropeptide Y, a potential marker for lupus, promotes lupus development

ObjectiveRelationship between neuropeptide Y (NPY) serum levels, NPY genetic mutation with systemic lupus erythematosus (SLE) pathogenesis is yet to be clarified, and role of NPY in development of SLE needs elucidation. MethodThis study included 460 SLE patients, 472 non-SLE cases, 500 healthy volunteers. Serum NPY, matrix metalloproteinase-1 (MMP-1) and MMP-8 levels were tested by ELISA. Genotyping 7 NPY single nucleotides polymorphisms (SNPs) (rs5573, rs5574, rs16129, rs16138, rs16140, rs16147, rs16478) was obtained by Kompetitive Allele-Specific PCR (KASP) method. Pristane-induced lupus mice were treated with NPY-Y1 receptor antagonist, and histological analysis, serological changes of the mice were evaluated. ResultsNPY serum concentrations were significantly increased in SLE patients when compared to that in healthy volunteers, non-SLE cases. Rs5573 G allele, rs16129 T allele, rs16147 G allele frequencies were significantly different between SLE cases and healthy controls. Rs5574 TT + TC genotypes were related to levels of IgG, C3, C4 and erythrocyte sedimentation rate, and rs16138 GG + GC genotypes correlated with SLE cases with anti-double-stranded deoxyribonucleic acid antibody (anti-dsDNA) (+). Serum MMP-1, MMP-8 concentrations were higher in SLE patients, and NPY levels were significantly related to MMP-1, MMP-8 levels. After treatment of lupus mice with NPY-Y1 receptor antagonist, damage of liver, spleen and kidney was alleviated, production of autoantibodies (anti-nuclear antibody (ANA), total IgG, anti-dsDNA) and MMP-1, MMP-8 was down-regulated, and differentiation of CD3+, CD8+ T cells, B cells, monocytes, macrophages, T helper 1 (Th1), Th2, Th17 cells was reversed. ConclusionNPY may be a biomarker for lupus, which may promote occurrence and development of lupus.

Correlation of hematological parameters, antibodies and cytokines with disease activity in systemic lupus erythematosus: a cross-sectional study

BackgroundThe aim of the study was to investigate the association of neutrophil-to-lymphocyte (NLR) and platelet-to-lymphocyte ratios (PLR) with standard inflammation parameters, including erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), complement component C3, anti-double-stranded deoxyribonucleic acid (anti-dsDNA), anti-nucleosome and anti-C1q antibodies, and serum and urinary monocyte-chemoattractant protein-1 (MCP-1) with disease activity in patients with systemic lupus erythematosus (SLE).ResultsThis study included 160 patients (145 female and 15 male patients), hospitalized at the Rheumatology Department. A positive correlation between NLR and ESR (p < 0.01), anti-dsDNA antibodies (p < 0.05), and PLR (p < 0.001) was obtained, with a negative correlation with C3 (p < 0.005). PLR shows a positive correlation with ESR (p < 0.001), CRP (p < 0.005), anti-dsDNA antibodies (p < 0.001), anti-nucleosome antibodies (p < 0.05), and urine MCP-1 (p < 0.05), with a negative correlation with C3 (p < 0.005). Univariate analysis showed that all the examined laboratory parameters were independent predictors of disease activity (p < 0.001), while the method of standard multiple regression analysis revealed the most significant ESR and serum MCP-1 (p < 0.05).ConclusionsNLR and PLR, as inexpensive and accessible biomarkers, can help in routine clinical practice for the estimation of disease activity in SLE patients.

The Immunodiagnostic Utility of Antinuclear Antibody Patterns: A Prediction for Renal Involvement in Systemic Lupus Erythematosus Patients in the Western Region of Saudi Arabia.

Objectives Previous studies have noted associations between the immunofluorescence patterns of antinuclear autoantibodies (ANA) and the autoimmune responses seen in systemic lupus erythematosus (SLE). In this study, the authors tested the hypothesis of whether ANA patterns predict renal involvement in SLE patients. Method A retrospective study was carried out on consecutive SLE patients who had ANA staining pattern dataand who were screened for renal involvement defined as all-stage proteinuria or chronic kidney disease (CKD) at a referral tertiary center in western Saudi Arabia from December 2021 to February 2022. Demographic data and levels of lupus immune markers including ANA titers, anti-double-stranded deoxyribonucleic acid antibodies (anti-dsDNA), complements C3 and C4, anticardiolipin (aCL) immunoglobulin (Ig) G and IgM, anti-β2 glycoprotein (β2-IgM and β2-IgG), and lupus anticoagulant (LA) antibodies were collected. Result Among 243 patients included, 25.1% had renal involvement (95% confidence interval {CI}=19.8-31.0). A mixed ANA pattern was associated with a higher prevalence of renal involvement (46.2%), followed by homogenous (26.5%) and speckled (25.6%) patterns, compared with 4.5% for the other patterns (p=0.044). No further association of renal involvement was observed with other biological markers. Adjusted logistic regression showed age (odds ratio {OR}=0.95; 95% CI=0.92-0.97) and mixed ANA pattern (OR=26.66; 95% CI=2.53-281.11) to be independently associated with renal involvement, explaining 12.6% of the variance. Conclusion A mixed homogenous/speckled ANA staining pattern is associated with an increased risk of renal involvement, independent of ANA titer or other lupus immune markers. The potential clinical applications of the ANA staining pattern in SLE should be explored in various subtypes of SLE and patient groups.

Dysregulated balance in Th17/Treg axis of Pristane-induced lupus mouse model, are mesenchymal stem cells therapeutic?

Despite advances in general and targeted immunosuppressive therapies, limiting all mainstay treatment options in refractory systemic lupus erythematosus (SLE) cases has necessitated the development of new therapeutic strategies. Mesenchymal stem cells (MSCs) have recently emerged with unique properties, including a solid propensity to reduce inflammation, exert immunomodulatory effects, and repair injured tissues. An animal model of acquired SLE mice was induced via intraperitoneal immunization with Pristane and affirmed by measuring specific biomarkers. Bone marrow (BM) MSCs were isolated from healthy BALB/c mice and cultured in vitro, then were identified and confirmed by flow cytometry and cytodifferentiation. Systemic MSCs transplantation was performed and then several parameters were analyzed and compared, including specific cytokines (IL-17, IL-4, IFN-ɣ, TGF-β) at the serum level, the percentage of Th cell subsets (Treg/Th17, Th1/Th2) in splenocytes, and also the relief of lupus nephritis, respectively by enzyme-linked immunosorbent assay (ELISA), flow cytometry analysis and by hematoxylin & eosin staining and also immunofluorescence assessment. Experiments were carried out with different initiation treatment time points (early and late stages of disease). Analysis of variance (ANOVA) followed by post hoc Tukey's test was used for multiple comparisons. The rate of proteinuria, anti-double-stranded deoxyribonucleic acid (anti-dsDNA) antibodies, and serum creatinine levels decreased with BM-MSCs transplantation. These results were associated with attenuated lupus renal pathology in terms of reducing IgG and C3 deposition and lymphocyte infiltration. Our findings suggested that TGF-β (associated with lupus microenvironment) can contribute to MSC-based immunotherapy by modulating the population of TCD4+ cell subsets. Obtained results indicated that MSCs-based cytotherapy could negatively affect the progression of induced SLE by recovering the function of Treg cells, suppressing Th1, Th2, and Th17 lymphocyte function, and downregulating their pro-inflammatory cytokines. MSC-based immunotherapy showed a delayed effect on the progression of acquired SLE in a lupus microenvironment-dependent manner. Allogenic MSCs transplantation revealed the ability to re-establish the balance of Th17/Treg, Th1/Th2 and restore the plasma cytokines network in a pattern dependent on disease conditions. The conflicting results of early versus advanced therapy suggest that MSCs may produce different effects depending on when they are administered and their activation status.

Performance evaluation of immunoblot for the detection of anti-DNA antibodies compared to indirect immunofluorescence on Crithidia luciliae

Systemic lupus erythematosus is a severe autoimmune disease preferentially affecting the female sex. Because of the great polymorphism of the disease, the diagnosis of lupus must first be confirmed on the basis of several clinico-biological criteria. Among the biological criteria is the presence of anti-dsDNA (double stranded Deoxyribonucleic acid) antibodies. The detection of these autoantibodies requires the use of techniques with high sensitivity and specificity. We evaluated the performance of the immunoblot technique (ANA-IB) in comparison with the indirect immunofluorescence technique (CLIFT) in the detection of anti-dsDNA antibodies in 100 sera. This comparison led to the conclusion that CLIFT remains the reference method for the detection of these antibodies and cannot be replaced by ANA-IB. However, their concomitant use increases the specificity of the test.

Profiling of kidney involvement in systemic lupus erythematosus by deep learning using the National Database of Designated Incurable Diseases of Japan

BackgroundKidney involvement frequently occurs in systemic lupus erythematosus (SLE), and its clinical manifestations are complicated. We profiled kidney involvement in SLE patients using deep learning based on data from the National Database of Designated Incurable Diseases of Japan.MethodsWe analyzed the cross-sectional data of 1655 patients with SLE whose Personal Clinical Records were newly registered between 2015 and 2017. We trained an artificial neural network using clinical data, and the extracted characteristics were evaluated using an autoencoder. We tested the difference of population proportions to analyze the correlation between the presence or absence of kidney involvement and that of other clinical manifestations.ResultsData of patients with SLE were compressed in a feature space in which the anti-double-stranded deoxyribonucleic acid (anti-dsDNA) antibody titer, antinuclear antibody titer, or white blood cell count contributed significantly to distinguishing patients. Many SLE manifestations were accompanied by kidney involvement, whereas in a subgroup of patients with high anti-dsDNA antibody titers and low antinuclear antibody titers, kidney involvement was positively and negatively correlated with hemolytic anemia and inflammatory manifestations, respectively.ConclusionAlthough there are various combinations of SLE manifestations, our study revealed that some of them are specific to kidney involvement. SLE profiles extracted from the objective analysis will be useful for categorizing SLE manifestations.

Population model-based analysis of the memory B-cell response following belimumab therapy in the treatment of systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by B-cell hyperactivity and breach of tolerance. Autoreactive memory B cells, which have a decreased activation threshold and the ability to survive in absence of antigen, are believed to contribute to chronicity in autoimmune diseases like SLE. Belimumab, the first approved biological treatment of active SLE and lupus nephritis, reduces B cells dependent on B-lymphocyte stimulator protein (BLyS) for survival, whereas memory B cells are spared; several studies reported circulating memory B-cell concentrations increase following BLyS neutralization. This analysis investigated the effect of dose, demographics, and disease status on memory B-cell response after starting belimumab treatment. Population pharmacodynamic models were fitted to a pooled dataset from seven belimumab SLE trials. The optimal model was selected using maximum likelihood methods and was then refit to the data using Bayesian analysis and used to simulate memory B-cell response by belimumab dose and covariate subgroups. At the belimumab approved doses (10mg/kg intravenously every 4 weeks, 200 mg subcutaneously every week), circulatory memory B cells increase in the first 4-8 weeks after belimumab initiation, typically returning to baseline levels over 76 weeks. The model analysis suggested belimumab stimulates memory B-cell transition from lymphoid and/or inflamed tissues into the circulation, rather than inhibiting trafficking in the reverse direction. Baseline BLyS and anti-double-stranded deoxyribonucleic acid antibody concentrations were statistically identifiable covariates of memory B-cell response, although their impact on predicting size and response duration was small.

Serum cystatin C and βeta-2 microglobulin as potential biomarkers in children with lupus nephritis.

In this study, we aimed to assess serum levels of Cystatin C (Cys C) and beta-2 microglobulin (β2M) in juvenile systemic lupus erythematosus (JSLE) patients and to investigate their role as potential biomarkers of lupus nephritis (LN) and overall disease activity. Between December 2018 and November 2019, a total of 40 patients with JSLE (11 males, 29 females; mean age: 12.6±2.5 years; range, 7.5 to 16 years) and 40 age- and sex-matched controls (10 males, 30 females; mean age: 12.3±2.4 years; range, 7 to 16 years) were included in this study. Serum (s) Cys C and β2M levels were compared between the groups. The SLE Disease Activity Index (SLEDAI-2K), the renal SLEDAI (rSLEDAI), and the Renal Damage Index were used. JSLE patients had significantly elevated mean sCyc C and sβ2M levels (1.4±0.8 mg/mL and 2.8±0.9 mg/mL, respectively) compared to the controls (0.6±0.1 mg/mL and 2.0±0.2 mg/mL, respectively; p<0.00). The mean sCys C and sβ2M levels were significantly higher in the LN group, compared to non-LN patients (1.8±0.7 mg/mL and 3.1±1.0 mg/mL, respectively vs. 0.8±0.3 mg/mL and 2.4±0.6 mg/mL, respectively; p=0.002 and p=0.02, respectively). The sCys C levels had significant positive correlations with erythrocyte sedimentation rate (r=0.3, p=0.05), serum creatinine (r=0.41, p= 0.007), 24-h urinary protein (r=0.58, p<0.001), anti-double stranded deoxyribonucleic acid antibodies titers (r=0.55, p=0.002), extra-renal SLEDAI scores (r=0.36, p=0.04), rSLEDAI (r=0.46, p=0.002), and renal class (r=0.7, p=0.0001). Serum β2M levels were significantly negatively correlated with complement 4 levels (r=-0.31, p=0.04) and significantly positively correlated with extra-renal SLEDAI scores (r=0.3, p=0.05). These findings confirm that sCys C and sβ2M levels are increased in JSLE patients in association with the overall active disease. However, sCys C level may act as a promising non-invasive biomarker for predicting kidney disease activity and biopsy classes in children with JSLE.

Primary and secondary antiphospholipid syndrome characteristics in an Egyptian cohort

Aim of the workTo describe the clinical and laboratory characteristics of patients with primary and secondary antiphospholipid syndrome (APS) in an Egyptian cohort. Patients and methodsSixty APS patients were enrolled. 12 had primary APS and 48 had secondary. Patients were further classified according to the presence of double or triple antiphospholipid antibodies (aPL). ResultsThe study included 55 (91.7 %) females and 5 (8.3 %) males, with a mean age of 33.9 ± 9.1 years, and mean disease duration of 6.2 ± 93.04 years. The obstetric complication in the form of fetal loss was the commonest manifestation of APS (70 %), followed by lower limb deep venous thrombosis (DVT) (50 %), recurrent abortion (45 %), thrombocytopenia (25 %), cutaneous manifestations (20 %), and Raynaud’s phenomenon (18.3 %). Urinary findings are mostly related to secondary APS. 15 (25 %) patients were thrombocytopenic and 1 (1.7 %) had autoimmune hemolytic anemia. Primary APS patients showed higher frequency of cutaneous manifestations compared to secondary (50 % vs 12.5 %; p = 0.04), and higher levels of β2 glycoprotein I IgG (71.8 ± 22.4 U/ml vs 59.3 ± 17.1 U/ml; p = 0.047). Secondary APS patients showed positive antinuclear antibodies (ANA) and anti-double stranded deoxyribonucleic acid antibodies (anti-dsDNA) in 97.9 % and 93.8 % respectively and were negative in all primary APS patients. On comparing patients with double (n = 34) and triple (n = 26) aPL, no differences were found between both groups except for platelet count being significantly lower in the triple aPL (p = 0.045). ConclusionEgyptian APS patients showed a high frequency of obstetric complications and lower limb DVT. Primary APS patients had higher frequency of cutaneous manifestations.

Prevalence of Anti-nuclear and Anti-phospholipid Antibodies in an Egyptian Cohort with Schizophrenia: A Case-control Study.

Psychiatric disorders, including schizophrenia, could herald other manifestation( s) of systemic lupus erythematosus (SLE) potentially hindering timely and optimal management. Moreover, schizophrenia is among the described 'extra-criteria' manifestations of anti-phospholipid syndrome (APS). Hence, screening schizophrenia patients for SLE and APS may pose diagnostic and therapeutic implications. Examine schizophrenia patients with no overt connective tissue disease(s) manifestation( s) for clinical and/or serologic evidence of SLE and/or APS. The study included 92 schizophrenia patients (61 (66.3%) males) and 100 age- and gender- matched healthy controls. Both groups were tested for anti-nuclear antibodies (ANAs), antidouble stranded deoxyribonucleic acid (anti-dsDNA) antibodies, complement 3 (C3) and C4, and criteria anti-phospholipid antibodies (aPL) (anticardiolipin Immunoglobulin (Ig) G and IgM, antibeta- 2-glycoprotein I IgG and IgM, and lupus anticoagulant (LAC)). The patients' mean age and disease duration were 28.8 ± 8.1 and 5.7 ± 2.2 years, respectively. The prevalence of ANA positivity, height of titre, and pattern was comparable between patients and controls (p = 0.9, p = 0.8 and p = 0.1, respectively). Anti-dsDNA antibodies and hypocomplementemia were absent in both groups. A significantly higher frequency of positive LAC was observed among patients compared with controls (7.6% vs. 1%, p = 0.02), whereas other aPL were comparable between both groups. None of the patients or controls demonstrated clinically meaningful (medium or high) aPL titres. In our study, schizophrenia was solely associated with LAC. Thus, in the absence of findings suggestive of SLE or APS, routine screening for both diseases is questionable.

Effects of Lactobacillus plantarum HFY15 on Lupus Nephritis in Mice by Regulation of the TGF-β1 Signaling Pathway.

ObjectiveIn this study, the Lactobacillus plantarum HFY15 (LP-HFY15) strain isolated from naturally fermented yak yogurt was investigated. An animal model of lupus nephritis was established by pristane to verify the interventional effect of LP-HFY15 on mouse lupus nephritis by regulating the transforming growth factor-β1 (TGF-β1) signaling pathway.Materials and MethodsIndexes in mouse serum and tissues were detected by kits, pathological changes in mouse kidney were observed by hematoxylin-eosin (H&E) staining, and quantitative polymerase chain reaction (qPCR) was used to detect TGF-β 1-related expression in mouse kidney tissue, which further elucidated the mechanism of LP-HFY15.ResultsLP-HFY15 decreased the elevation of urinary protein and the levels of interleukin-6 (IL-6), IL-12, tumor necrosis factor alpha (TNF-α), and interferon γ (IFN-γ) in serum and kidney tissue. LP-HFY15 also reduced serum creatinine (SCr), blood urea nitrogen (BUN), total cholesterol (TC), triglyceride (TG), and raised total protein (TP), and albumin (ALB) levels in mice with nephritis. In addition, LP-HFY15 inhibited the positive rate of double-stranded deoxyribonucleic acid (dsDNA) antibodies in mice with nephritis. The observation of H&E sections showed that LP-HFY15 alleviated the glomerulus morphological incompleteness and inflammatory infiltration caused by nephritis. Further results showed that LP-HFY15 downregulated the mRNA expression of TGF-β1, vascular endothelial growth factor (VEGF), and nuclear factor kappa-B (NF-κB) in the kidneys of lupus nephritis mice, and the expression of inhibitor of NF-κB (IκB-α), copper/zinc superoxide dismutase (Cu/Zn-SOD), and manganese superoxide dismutase (Mn-SOD) was also upregulated.ConclusionThese results indicated that LP-HFY15 plays a significant role in experimental intervention for lupus nephritis. The effect of LP-HFY15 was positively correlated with its concentration, and the effect was similar to that of prednisone at 109 CFU/kg.

Anti-double stranded DNA antibodies: A rational diagnostic approach in limited-resource settings

ContextAnti-double-stranded deoxyribonucleic acid antibodies (dsDNA Abs) are highly specific markers of systemic lupus erythematosus (SLE). Multiple methods are employed for their detection in routine diagnostics. ObjectivesThe aim of this study was to evaluate a diagnostic approach for anti-dsDNA Abs using DNA-ELISA and Crithidia luciliae fluorescence test (CLIFT), in combination with antinuclear antibody (ANA) screening. MethodsWe enrolled 113 patients—53 with SLE, 50 with other systemic autoimmune rheumatic diseases (OSARD), and 10 with non-autoimmune clinical conditions (NAICC).Patients’ samples were tested for anti-dsDNA Abs using an enzyme-linked immunosorbent assay (ELISA) and CLIFT, combined to ANA screening by indirect immunofluorescence assay (ANA-IIFA). ResultsThe mean age of patients was 39.94 ± 15 years (ranges: 11–85 years). Overall, specimens from 77.3%, 11.7%, and 20% of patients with SLE, OSARD and NAICC respectively were ELISA-positive; and those from 54.7% to 4% of patients with SLE and OSARD, respectively, were CLIFT-positive. CLIFT positivity was significantly associated with high ELISA titers (p = 0.002) and homogeneous ANA-IIF pattern (p = 0.0002). ConclusionFor better clinical relevance of anti-dsDNA antibodies, we suggest a combined detection strategy based on ELISA, CLIFT and ANA-IIFA, considering the clinical criteria of SLE.

A Young Woman with Anemia and Thrombocytopenia

&lt;p&gt;本文描述一位32歲女性病患，罹患全身性紅斑性狼瘡已有11年，規則於門診追蹤，因發燒、關節痛、胸痛，實驗室檢查發現貧血、血小板低下、補體（C3）低下、高效價之抗雙股去氧核糖核酸抗體（anti-dsDNA &gt; 379 IU／mL）、尿液呈現蛋白尿，初步診斷懷疑全身性紅斑性狼瘡復發。靜脈注射高劑量methylprednisolone七天，血小板仍偏低，治療反應差。本個案實驗室檢查顯示溶血性貧血、血小板低下、週邊血液抹片顯示碎裂紅血球，確定微血管性溶血性貧血證據，且血液中ADAMTS 13嚴重缺乏其血中活性為0%，因此診斷為血栓性血小板低下紫斑症。緊急接受血漿置換術，同時持續高劑量類固醇與靜脈注射Rituximab治療，因而血小板上升、乳酸脫氫脢大幅下降、貧血改善，達到治療的成效。全身性紅斑性狼瘡同時出現血栓性血小板低下紫斑症，經緊急啟動血漿置換，會降低病人的死亡率。&lt;/p&gt; &lt;p&gt;&amp;nbsp;&lt;/p&gt;&lt;p&gt;A 32-year-old female patient in this study, who suffered from systemic lupus erythematosus (SLE) for 11 years. Upon a regular rheumatology outpatient follow-up, she presented not only with fever,arthralgia and chest pain, but also with anemia, low platelets, low complement (C3), and high titer anti-double-strand deoxyribonucleic acid antibody (anti-dsDNA &gt; 379 IU/mL) on laboratory test report,as well as proteinuria on urinalysis. Accordingly, her condition was suspected to be a relapse of SLE. Unfortunately, after treatment with high-dose intravenous methylprednisolone, the response was poor with persistent low platelet level. Besides, hemolytic anemia and thrombocytopenia were noted and peripheral blood smear examination also showed fragmented red blood cells, supporting the diagnosis of microangiopathic hemolytic anemia. Moreover, there was severe ADAMTS13 deficiency in the blood, even with 0% of activity. Therefore, the patient was finally diagnosed with thrombotic thrombocytopenic purpura and then received urgent plasmapheresis in combination with high-dose glucocorticoid and of intravenous rituximab treatment. After the treatment, the platelet level increased, lactate dehydrogenase level remarkably decreased, and anemia gradually improved. Taken together, urgent initiation of plasma exchange together with glucocorticoid and rituximab treatment for SLE patient with thrombotic thrombocytopenic purpura could lower the mortality rate.&lt;/p&gt; &lt;p&gt;&amp;nbsp;&lt;/p&gt;

Clinical study of factors associated with pregnancy outcomes in pregnant women with systemic lupus erythematosus in the southern China.

Objectives This study aims to estimate predicted factors for maternal and fetal outcomes in Hakka pregnant women with systemic lupus erythematosus (SLE) in the southern China.Patients and methods Between June 2014 and February 2020, we retrospectively analyzed the data of a total of 123 singleton pregnant women with SLE (mean age: 27.1±4.1 years; range, 19 to 39 years) who were referred to our rheumatology clinic. Demographic, clinical, and laboratory data of the patients were recorded. Adverse pregnancy outcomes (APOs) were assessed.Results Multivariate logistic regression analysis revealed that preeclampsia was associated with the increased odds of APOs (odds ratios [OR]=9.538, 95% confidence interval [CI]: 2.055-44.271, p=0.004), premature birth (OR=14.289, 95% CI: 3.596-56.777, p<0.001) and low birth weight (OR=8.275, 95% CI: 2.117-32.345, p=0.002). Anti-double-stranded deoxyribonucleic acid (anti-dsDNA) antibody positivity was the predictor of APOs (OR=2.165, 95% CI: 1.034-4.532, p=0.040), premature birth (OR=2.849, 95% CI: 1.220-6.657, p=0.016) and pregnancy loss (OR=3.004, 95% CI: 1.086-8.305, p=0.034). The use of hydroxychloroquine and prednisone was associated with the decreased odds of APOs (OR=0.412, 95% CI: 0.198-0.860, p=0.018) and pregnancy loss (OR=0.304, 95% CI: 0.111-0.831, p=0.020).Conclusion Our study results indicate that preeclampsia, anti-dsDNA antibody positivity, and the use of hydroxychloroquine and prednisone are independent predictors of pregnancy outcomes.

Systemic lupus erythematosus after coronavirus disease-2019 (COVID-19) infection: Case-based review

BackgroundCoronavirus disease-2019 (COVID-19) is a novel infectious disease, which presents with various clinical manifestations. There is growing evidence of an association between COVID-19 infection and autoimmune diseases. The aim of this case report was to demonstrate the association of COVID-19 infection and the development of systemic lupus erythematosus (SLE). Case presentationA 38 year old Iranian woman presented with progressive icterus, pleuritic chest pain, palpitation, dyspnea, photosensitivity and arthralgia 18-days after COVID-19 symptoms proved by a positive polymerized chain reaction (PCR). The chest and abdomen computerized tomography (CT) scan showed pericardial and pleural effusion and enlarged liver and abdominal lymph nodes. Antinuclear antibody (ANA), anti-double stranded deoxyribonucleic acid (anti-ds DNA) antibody and perinuclear anti-neutrophil cytoplasmic antibody (P-ANCA) were positive. She was diagnosed as SLE and was successfully treated with prednisolone 30 mg daily, hydroxychloroquine 200 mg daily and azathioprine 150 mg daily and she remarkably improved. Repeated anti-ds DNA antibody was positive. Due to nausea and abdominal discomfort, azathioprine was discontinued and replaced with mycophenolate mofetil 1500 mg daily. In the article, similar cases were presented; the mean interval between COVID symptoms and SLE presentations was 24.86 days. Pulmonary and renal involvements were the most common presentations of SLE triggered by COVID-19. The most frequently reported autoantibody was ANA ConclusionIt is necessary to be aware of the development of lupus disease in COVID-19 infected patients, because prompt diagnosis and treatment is very important to improve their outcome.

Systemic lupus erythematous presenting with hemorrhagic shock caused by gastric penetration of pancreatic pseudocyst: a case report

BackgroundSystemic lupus erythematous that causes various organ damage is rarely associated with pancreatic lesion. To the best of our knowledge, no cases presenting with hemorrhage shock caused by gastric penetration of pancreatic pseudocyst due to lupus pancreatitis have been reported. Herein, we report a case of hemorrhage shock caused by gastric penetration of pancreatic pseudocyst due to lupus pancreatitis.Case presentationA 53-year-old Japanese man with a history of systemic lupus erythematous, pancreatic pseudocyst, and chronic pancreatitis complained of epigastric pain and had hematemesis. He visited our emergency room and was admitted in our hospital. Upper endoscopy showed that hemostasis was obtained; however, computed tomography scan was performed since he was suspected to have gastric penetration into hollow viscera. The computed tomography revealed accumulation of fluid around the pancreas and gastric penetration of pancreatic cyst. Blood test showed increased serum amylase level. These results suggest that the exacerbation of chronic pancreatitis causes the penetration. Surgery was considered; however, we took a wait-and-see approach since hemostasis was obtained. After that, he was in stable condition, although he suffered from fever and accumulation of left pleural effusion was observed by computed tomography. However, he had massive hematemesis and melena 9 days after hospitalization and died in spite of several treatments including blood transfusion. Autopsy revealed that he actually had pleural thickening, which is not caused by accumulation of left pleural effusion but by severe pleural inflammation. We therefore performed additional blood and urinary tests on the same day. The test results showed that he had a high titer of anti-double-stranded deoxyribonucleic acid (DNA) antibody, hypocomplementemia, and erythrocyturia, indicating that he had systemic lupus erythematous with high disease activity considering his fever and pleural inflammation.ConclusionsPatients who have systemic lupus erythematous with high disease activity have the potential to develop fatal complications due to pancreatitis, so appropriate treatments are required for such patients.