Antidouble-stranded DNA Antibodies Research Articles

#1267 Exostosin 1- and 2-positive membranous nephropathy in Chinese patients

Abstract Background and Aims The exostosin 1 and 2 (EXT1/2) complex was recently identified as a potential antigen associated with systemic autoimmunity in PLA2R-negative membranous nephropathy patients. There are currently no reports of circulating anti-EXT1/2 antibodies and no clinical studies of EXT1/2-positive membranous nephropathy in the Chinese population. Method Immunohistochemical staining for PLA2R, THSD7A and NELL-1 was performed in 1442 consecutive patients with biopsy-proven MN from January 2011 to December 2019 at Beijing Anzhen Hospital. A total of 201 MN patients were PLA2R-, THSD7A- and NELL-1-negative and enrolled in the study. Patient medical records were reviewed for clinical data, including demographics, laboratory tests, treatment, and follow-up. The glomerular expression of EXT1 and EXT2 was screened. The anti-EXT1 and anti-EXT2 antibodies were also detected in the sera of patients with EXT1/2–positive membranous nephropathy by western blot, ELISA and immunoprecipitation separately. Clinical and pathologic features were comparable between PLA2R-, THSD7A- and NELL-1-negative patients with EXT1/2 or without EXT1/2 positive. Results Among these 201 patients, 19 of 83 (22.9%) with lupus membranous nephropathy (class 5 and class 5+3/4), and 13 of 118 (11.0%) with nonlupus membranous nephropathy exhibited positive EXT1/2 staining. Thirteen patients with EXT1/2-positive non-LMN had no definitive secondary cause, but 7 patients (53.8%, 7/13) were seropositive for ANA. Baseline anti–double-stranded DNA antibody and serum antinuclear antibody positivity were independent predictors of glomerular EXT1/2-positive expression in patients with lupus membranous nephropathy (pure class 5, class 5 + 3/4) and nonlupus membranous nephropathy, respectively. In 32 patients with EXT1/2-positive MN, 22 patients with available serum samples collected at the time of biopsy were tested for anti-EXT1 and anti-EXT2 antibodies. Sixteen patients were positive for antibodies. According to the molecular weight of positive bands, we speculated that 5 patients were positive for both anti-EXT1 and anti-EXT2 antibodies, 11 patients were positive only for anti-EXT1 antibodies, and no patients were positive only for anti-EXT2 antibodies. There were no significantly differences between the characteristics of 22 EXT1/2-positive MN patients with or without antibody seropositivity. Two patients with EXT1/2-positive membranous nephropathy underwent repeated renal biopsies. When the pathological type changed to lupus nephritis (LN) or the LN worsened clinically, the renal tissue staining intensity of EXT1/2 increased. Renal EXT1/2 staining positivity occurred earlier than the diagnosis of lupus. Conclusion This is the first study to detect circulating anti-EXT1/2 antibodies, and the functional significance should be further studied. The renal EXT1/2 staining positive was earlier than diagnosis of lupus. whether the level of serum EXT1/2 antibody can be used as a predictor for disease progression and prognosis needs to be further evaluated in larger sample studies.

Machine learning approaches to identify systemic lupus erythematosus in anti-nuclear antibody-positive patients using genomic data and electronic health records

BackgroundAlthough the 2019 EULAR/ACR classification criteria for systemic lupus erythematosus (SLE) has required at least a positive anti-nuclear antibody (ANA) titer (≥ 1:80), it remains challenging for clinicians to identify patients with SLE. This study aimed to develop a machine learning (ML) approach to assist in the detection of SLE patients using genomic data and electronic health records.MethodsParticipants with a positive ANA (≥ 1:80) were enrolled from the Taiwan Precision Medicine Initiative cohort. The Taiwan Biobank version 2 array was used to detect single nucleotide polymorphism (SNP) data. Six ML models, Logistic Regression, Random Forest (RF), Support Vector Machine, Light Gradient Boosting Machine, Gradient Tree Boosting, and Extreme Gradient Boosting (XGB), were used to identify SLE patients. The importance of the clinical and genetic features was determined by Shapley Additive Explanation (SHAP) values. A logistic regression model was applied to identify genetic variations associated with SLE in the subset of patients with an ANA equal to or exceeding 1:640.ResultsA total of 946 SLE and 1,892 non-SLE controls were included in this analysis. Among the six ML models, RF and XGB demonstrated superior performance in the differentiation of SLE from non-SLE. The leading features in the SHAP diagram were anti-double strand DNA antibodies, ANA titers, AC4 ANA pattern, polygenic risk scores, complement levels, and SNPs. Additionally, in the subgroup with a high ANA titer (≥ 1:640), six SNPs positively associated with SLE and five SNPs negatively correlated with SLE were discovered.ConclusionsML approaches offer the potential to assist in diagnosing SLE and uncovering novel SNPs in a group of patients with autoimmunity.

#2598 KLOTHO DEFICIENCY INDUCES REGULATORY T CELLS IN MURINE LUPUS NEPHRITIS

Abstract Background and Aims Recent studies demonstrate that klotho deficiency participate in various chronic kidney disease. However, it has not been fully assessed the influence of klotho in autoimmune kidney diseases. On the one hand, klotho is known to binds transforming growth factor β (TGFβ) receptor to antagonize its pathophysiological actions including renal fibrosis. On the other hand, TGFβ is required to generate and maintain regulatory T cells with inducing FOXP3, an important cell population for immunological tolerance. Method NZBWF1 mice were used as a model of lupus nephritis. NZBWF1 mice were housed separately in metabolic cage, and divided into two groups (n=10 for each): one group was treated with daily subcutaneous injection of klotho protein (20 µg/kg/day), and the other received vehicle alone. Systolic blood pressure was measured by tail-cuff method. Glomerular filtration rate was assessed using FITC-inulin. Four weeks later, the animals were killed to harvest the spleen and kidneys for analyses. Results Klotho supplementation suppressed blood pressure, 8-epi-prostaglandin F2a excretion and renal angiotensin II levels (p<0.05 for all) without changes in albuminuria and glomerular filtration rate in NZBWF1 mice. Exogenous klotho protein supplementation increased serum klotho levels, urine klotho excretion, and endogenous renal expression of klotho in NZBWF1 mice (p<0.05 for all). Surprisingly, anti-double strand DNA antibody was slightly elevated in klotho-treated NZBWF1 mice (p<0.05). Glomerular pathology and interstitial cell infiltration were similar between 2 groups. The spleen tended to be greater in klotho-treated group, but statistical significance was not attained. In consistent, CD8+FOXP3+ T cells were unaltered between 2 groups. However, klotho supplementation reduced CD4+FOXP3+ T cells in spleen of NZBWF1 mice (p<0.05). Conclusion The present data indicated that klotho protein supplementation suppressed renal renin-angiotensin system, ameliorating blood pressure and oxidative stress. Our results suggest that klotho supplementation worsened auto-antibody, possibly by inhibiting TGFβ with resultant deterioration in regulatory T cells. The present findings implicate that although klotho may not suite for the management of autoimmune kidney diseases, such as lupus and ANCA-related nephritis, klotho supplementation for dialysis patients could mitigate against the defect in cellular immunity and susceptibility to infections including tuberculosis and COVID-19.

Belimumab versus anifrolumab in adults with systemic lupus erythematosus: an indirect comparison of clinical response at 52 weeks

ObjectiveTo generate comparative efficacy evidence of belimumab versus anifrolumab in SLE that can inform treatment practices.MethodsThe SLE Responder Index (SRI)-4 response at 52 weeks of belimumab versus anifrolumab was evaluated...

Anti-double stranded DNA antibodies: Electrochemical isotyping in autoimmune and neurological diseases

This work reports the first amperometric biosensor for the simultaneous determination of the single or total content of the most relevant human immunoglobulin isotypes (hIgs) of anti-dsDNA antibodies, dsDNA-hIgG, dsDNA-hIgM, dsDNA-hIgA and dsDNA-three hIgs, which are considered relevant biomarkers in prevalent autoimmune diseases such as systemic lupus erythematosus (SLE) as well as of interest in neurodegenerative diseases such as Alzheimer's disease (AD). The bioplatform involves the use of neutravidin-functionalized magnetic microparticles (NA-MBs) modified with a laboratory-prepared biotinylated human double-stranded DNA (b-dsDNA) for the efficient capture of specific autoantibodies that are enzymatically labeled with horseradish peroxidase (HRP) enzyme using specific secondary antibodies for each isotype or a mixture of secondary antibodies for the total content of the three isotypes. Transduction was performed by amperometry (−0.20 V vs. the Ag pseudo-reference electrode) using the H2O2/hydroquinone (HQ) system after trapping the resulting magnetic bioconjugates on each of the four working electrodes of a disposable quadruple transduction platform (SP4CEs). The bioplatform demonstrated attractive operational characteristics for clinical application and was employed to determine the individual or total hIgs classes in serum from healthy individuals and from patients diagnosed with SLE and AD. The target concentrations in AD patients are provided for the first time in this work. In addition, the results for SLE patients and control individuals agree with those obtained by applying ELISA tests as well as with the clinical ranges reported by other authors, using individual detection methodologies restricted to centralized settings or clinical laboratories.

Transverse myelitis following bivalent COVID‐19 booster vaccine and quadrivalent seasonal influenza vaccine

Transverse myelitis following bivalent <scp>COVID</scp>‐19 booster vaccine and quadrivalent seasonal influenza vaccine

ESTIMATION AND TO KNOW THE ASSOCIATION OF AUTOANTIBODIES WITH DERMATOLOGICAL DISORDERS IN PATIENTS ATTENDING DERMATOLOGY OUTPATIENT DEPARTMENT

Background: The presence of antinuclear antibodies (ANA) is mainly associated with autoimmune diseases and connective tissue diseases (CTD). In addition, their presence is found in healthy people. While the actual frequency of positive assays in healthy individuals varies with methodology, nevertheless, up to 20% or more of otherwise healthy people can express an ANA. The basis of this seropositivity is puzzling. One possibility is that ANAreactivity represents vagaries of the assays, allowing the detection of antibodies of either low titer or low avidity. ANAand Anti double-stranded DNA (Anti-ds-DNA) antibodies in dermatological disorders other than CTD, and Vasculitis were not studied till now to our knowledge. Hence this study has been taken up. Aim: Estimation and to know the association, of autoantibodies with dermatological disorders, to better understand the diseases in patients attending the dermatology outpatient department (OPD). Objectives: 1. To nd out the percentage of positivity for ANAby the Indirect Immunouorescent Assay (IFA) method. 2. To nd out the percentage of positivity for anti-ds DNAantibodies by the Enzyme-Linked Immunosorbent Assay (ELISA) method. 3. Percentage of positivity of both ANAand Anti-ds DNAantibodies in patients with dermatological problems. 4. To know the association of autoimmunity with various dermatological disorders for a better understanding of these disorders. Materials &amp; Methods: Ahundred patients were selected after taking written informed consent and after inclusion and exclusion criteria got fullled. Details of the patients were entered in the case record form and later were uploaded in a Microsoft excel sheet. One millilitre of the venous blood sample was drawn in adults of each of the age categories 18-27, 28-37, 38-47, and 48-57. The upper age limit of 57 is selected for the sake of convenience. Sera were analysed for ANAand Anti ds DNAantibodies by using IFAand ELISAmethods respectively. Results were recorded and analysed. Results: In a total of 100 patients 11% and 13% were positive for ANA and Anti ds DNA respectively. For ANA and Anti ds DNA positivity the mean age was 34.5 ± 12.5 and 40.7 ± 10.7 respectively and females outnumbered males in both. Both ANAand Anti ds DNAwere positive in 3% of which all were females with a mean age of 41 ± 9. ANA positivity was found commonly in Telogen efuvium (3), melasma (2), and Tinea (2). Anti-ds DNA positivity was found commonly in Miliaria Rubra (2), and Tinea (2). Both ANAand Anti ds DNA were positive in telogen efuvium, melasma and tinea. Conclusion:ANA, Anti ds DNA, both ANAand Anti ds DNAwere positive in otherwise healthy dermatological patients with diagnoses like telogen efuvium, melasma, tinea, miliaria etc., to the extent of 11%, 13%, and 3% respectively. It is not known if autoantibody positivity in these diseases is just a chance association or if the autoimmune mechanism got triggered by these diseases. Prospective longitudinal studies are necessary to conrm these nding

Clinical efficacy and safety of sirolimus in childhood-onset systemic lupus erythematosus in real world.

To investigate the effectiveness and safety of sirolimus in childhood-onset systemic lupus erythematosus in a real world. This is a retrospective real world clinical study. All childhood-onset systemic lupus erythematosus patients treated with sirolimus in Children's Hospital of Hebei Province China were analyzed. They were treated with sirolimus and followed up regularly. The patients had systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score, levels of antidouble-stranded DNA antibody, complement components C3 and C4, 24-hour proteinuria and corticosteroid reduction were recorded at baseline and at 6, 12, and 18 months. Adverse events were also collected. Thirty-two patients were enrolled in the study. SLEDAI-2K were improved on all time-points (P < .05). Complement levels increased and the levels of antidouble-stranded DNA antibody decreased during treatment. The mean dose of prednisone tapered and achieved significant reduction after 12 months therapy (15.4 ± 5.8 mg/d to 4.8 ± 2.1 mg/d; P < .05). Sirolimus was well tolerated and only 5 patients (15.6%) experienced adverse events, all of which were classified as infections (2 bacterial infection and 3 viral infections). No deaths, severe infusion reactions, or hypersensitivity reactions were found. Sirolimus use was associated with a decrease in disease activity and ability to tolerate tapering of oral glucocorticoid dose with a favorable risk-benefit profile.

Amicrobial pustulosis of the folds mimicking Hailey-Hailey disease in a patient with systemic lupus erythematosus and Sjögren’s syndrome

Sir, Amicrobial pustulosis of the folds (APF) is a rare disease of neutrophilic dermatosis involving the scalp, ears, axillae, umbilicus, groin, and buttocks [1–3]. Herein, we describe a case of APF involving the bilateral axillae mimicking Hailey-Hailey disease in association with systemic lupus erythematosus (SLE) and Sjögren’s syndrome (SjS). A 63-year-old female had been undergoing treatment for SLE and SjS for six years. She had been taking prednisolone at a dose of 4 mg per day on the first visit to us. She also had a history of Crohn’s disease in remission. She complained of recurrent, erosive erythema on the axillae and beneath the breasts, which worsened in summer. A physical examination revealed infiltrative erythema with superficial erosions on the bilateral axillae (Figs. 1a and 1b). A laboratory examination revealed normal liver and kidney function, yet positive results for serum antinuclear antibodies (1:1280), anti-double strand DNA antibody (128 IU/mL), anti-Sm antibody (index: 6.7), anti-SS-A antibody (index: 131.5), and anti-SS-B antibody (index: 93.7). The erythrocyte sedimentation rate was high (32 mm in the first hour), and the CRP level was slightly increased (1.19 mg/dL). Bacterial cultures were positive for group G streptococci and the Corynebacterium species. A biopsy specimen did not reveal acantholysis of the epidermis, yet mild epidermal acanthosis without intense infiltration of inflammatory cells. Hailey-Hailey disease was excluded, and the patient was followed under treatment with topical corticosteroid ointment. During the course, the skin lesions exacerbated, and new pustules and erosive erythemas appeared on the groin and the anogenital areas (Fig. 1c). A histopathological examination revealed subcorneal neutrophilic abscesses in the epidermal and dermal perifollicular areas (Figs. 2a – 2d).

A 41-Year-Old Man With an Abdominal Mass and Hepatomegaly

A 41-Year-Old Man With an Abdominal Mass and Hepatomegaly

Assessment of Serum Neutrophil Gelatinase Associated Lipocalin (NGAL) levels in patients of Systemic Lupus Erythematosus (SLE) with and without Lupus Nephritis (LN)

Background: Lupus nephritis (LN) can occur as a complication of SLE causing further distress to patient. NGAL levels can help in foreseeing kidney injury in such afflicted. Thus, the study aimed to estimate serum NGAL levels in SLE patients with and without Lupus Nephritis. Methods: A cross sectional study was conducted at immunology Department, University of Health Sciences (UHS) Lahore. Purposive sampling technique was used to collect samples of patients diagnosed with SLE with and without Lupus Nephritis LN. Results: Study showed statistically significant results (p=0.00) with mean ±SD value of NGAL measured in patients of SLE with LN &amp; without Lupus Nephritis LN. Conclusion: The study indicated that NGAL level was observed to be significantly raised in the patients of SLE with lupus nephritis as compare to the patients of SLE without lupus nephritis. Keywords: Acute kidney injury, Anti-double stranded DNA antibody, Chronic kidney disease, Lupus nephritis

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.

Spectrum of Morphological and Immunofluorescence Patterns in Lupus Nephritis: A Single Institutional Study.

IntroductionLupus nephritis (LN) is a systemic manifestation of systemic lupus erythematosus (SLE). LN commonly occurs three to five years later after the onset of SLE and is one of the leading cause of end-stage renal disease. The objective of this study was to evaluate the spectrum of morphological and immunofluorescence (IF) patterns in LN.MethodologyA cross-sectional descriptive study was conducted on 58 renal core biopsies diagnosed as LN at Chughtai Institute of Pathology between January 2021 and December 2021. Based on the International Society of Nephrology and the Renal Pathology Society, prevalence of different classes of LN was assessed. The demographic, clinical, and biochemical parameters were analyzed in association with different histological classes of LN.ResultsIn our study, the male-to-female ratio was 1:6.5. The mean age was 23.09 ± 9.23 years. Increased serum urea levels were found in 36 (62.10%) patients, and increased serum creatinine levels were found in 43 (74.12%) patients. Nephritic range proteinuria was seen in 14 (24.10%) patients, while 44 (75.90%) patients had proteinuria in the nephrotic range. Anti-double stranded DNA antibody was positive in 49 (84.50%) patients. Microscopic hematuria was present in 46 (79.30%) patients. Main bulk of patients belong to class V, 25 (43.10%), followed by class IV, 16 (27.59%). Full-house IF pattern was seen in majority of patients.ConclusionThis study showed a high frequency of prevalence of advanced classes of LN, i.e., class V followed by class IV. There is a strong diagnostic utility of IF in LN. Similarly, full-house IF pattern was observed in majority of patients in our study, irrespective of which class of LN they belonged to.

The expanding role of synthetic nucleic acids for diagnosis and treatment.

The presence of autoantibodies is a characteristic and diagnostic index of systemic lupus erythematosus (SLE). Antidouble-stranded DNA (antids-DNA) antibodies are the most frequent autoantibodies found in SLE related to the diagnosis and disease activity of SLE, and are measured by established methods like ELISA as a polyclonal autoantibody. However, there is no reliable data on the relationship between the respective reactivity of these polyclonal antids-DNA antibodies against different epitopes generated from the original antigen and the disease phenotype. Of the complications in SLE, neuropsychiatric SLE (NPSLE) is a troublesome and frequent phenotype of the disease but no specific diagnostic autoantibodies in serum have been found. First in this review, the possibility of antids-DNA antibodies for identifying primary NPSLE in patients with SLE based on the reactivity of different synthetic nucleic acids is described as a diagnostic marker. The purpose of this review is to examine diagnostic and therapeutic opportunities to modulate autoimmune in the central nervous system (CNS) developing the CNS inflammatory disorders. Khatri et al. investigated antids-DNA antibodies in order to develop a reliable method based on the application of synthetic nucleic acids and protein-based antigen arrays to characterize autoreactive antibodies specially for NPSLE. They found autoantibodies in three particular synthetic double stranded antigens and the antinuclear antibody patterns in ordinary lupus and NPSLE. These discoveries are leading to precision medicine in the CNS inflammatory disorders. Verifying the similarity of antids-DNA obtained from patients with NPSLE can be useful as a diagnostic marker. mRNA vaccination can locally suppress autoimmunity in the CNS associated with critical steps for the develop of CNS autoinflammation. Synthetic nuclei acids may provide a diagnostic and therapeutic target in patients with autoimmune CNS inflammatory disorders.

Variable presentations of systemic lupus erythematosus based on presence or absence of antidouble stranded DNA antibodies: A case series

Systemic lupus erythematosus (SLE) presents with diverse clinical features causing diagnostic challenges. Apart from the clinical features, autoantibodies are important for diagnosis along with certain laboratory parameters. Diagnosis is made with the European League against Rheumatism/American College of Rheumatology 2019 Criteria. The case series presented here signifies the correlation between anti ds DNA positivity and its association with poor prognosis and renal disease, whereas antidouble stranded DNA (anti-dsDNA) negativity may lead to lack of renal involvement and may be associated with polyserositis. The importance lies in the fact that these patients with anti-dsDNA negativity should be followed up for assessing conversion to positivity of anti-dsDNA, thus altering the prognosis and leading to renal involvement. Moreover, anti-SSA positive SLE patients must be followed up for possible development of sicca symptoms.

Evaluation of Demographic, Clinical and Laboratory Features of Patients with Systemic Lupus Erythematosus in Kermanshah

Background: Systemic lupus erythematosus (SLE) is a worldwide autoimmune disease. The disease has different etiologies, clinical and laboratory symptoms between different geographical and racial groups, and sufficient knowledge of the type of symptoms in each region can play a proper role in diagnosis and treatment. Objectives: This study was performed to evaluate demographic, clinical and laboratory features of patients with systemic lupus erythematosus in Kermanshah. Methods: This study is descriptive, analytical and cross-sectional. The files of 150 patients with lupus during 2016 - 2018 in Imam Reza hospital in Kermanshah were reviewed. Results: Data analysis showed that patients at the time of referral were with musculoskeletal symptoms 37.3% (56 individuals), cutaneous-mucosal 32% (48 individuals), constitutional 51.3% (77 individuals), renal 62% (93 individuals), cardiac 6.7% (10 individuals), neurological manifestations 17.3% (26 individuals), pulmonary involvement 37.3% (56 individuals), and Hematological 71.3% (107 individuals). The anti-nuclear antibody (ANA) in 60% (90 individuals), anti-double strand DNA Antibody (anti-ds DNA) in 35.4% (53 individuals), C-reactive protein (CRP) in 44.6% (67 individuals), lower level of normal C3 and C4 in 33.3% (50 individuals) and 11.3% (17 individuals), respectively, lupus anticoagulant in 13.3% (20 individuals), antibody citrullinated peptide anti-cyclic (anti-CCP) in 14.9% (22 individuals), anticardiolipin IgM and IgG, in 6% (9 individuals) and 9.3% (14 individuals) of patients respectively were observed. Also, anemia was observed in 34% (51 individuals), leukopenia in 22% (33 individuals), and thrombocytopenia in 30.7% (46 individuals). Abnormal ESR (erythrocyte sedimentation rate) was seen in 59.3% (89 individuals) of patients. Leukopenia in men and positive CRP in women were more common (P = 0.014, P = 0.004). Conclusions: Despite the diverse clinical and laboratory manifestations of SLE in different racial and geographical groups, paying attention to these differences in each region can effectively diagnose the disease. As in this study, hematological manifestations had a higher percentage in the population of lupus patients in Kermanshah.

Comparison of Renal Responses Between Continuous Mycophenolate Mofetil and Conversion from Mycophenolate Mofetil to Enteric-Coated Mycophenolate Sodium in Lupus Nephritis.

BackgroundMycophenolate mofetil (MMF) is extensively used for induction and maintenance therapy in patients with lupus nephritis (LN). Enteric-coated mycophenolate sodium (EC-MPS) was developed to reduce the adverse gastrointestinal effects of MMF. However, the therapeutic efficacy of MMF and EC-MPS in LN remains unclear. This study aimed to examine the treatment effects of EC-MPS in LN patients with prior MMF exposure.MethodsIn this medical records review study, we included 54 LN patients, of whom 34 converted from MMF to EC-MPS at equimolar doses in 2016–2018 (nonmedical switching group) and 20 received continuous MMF treatment. Patients achieving complete remission or partial remission before the conversion were categorized as responders, whereas those who had never achieved complete remission or partial remission were categorized as nonresponders.ResultsBaseline proteinuria was higher in the nonmedical switching group. Although elevation in proteinuria was observed after nonmedical switching, the serum creatinine concentration and estimated glomerular filtration rate both improved. Responders in the nonmedical switching group had lower proteinuria and higher complement 3 levels. In the subgroup analysis, albeit the modest increase in daily urine protein, anti–double-stranded DNA antibody levels, estimated glomerular filtration rate, and complements 3 and 4 seemed comparable after conversion.ConclusionSwitching to EC-MPS demonstrated a similar short-term renal response to continuous MMF treatment in LN patients. Prospective randomized trials are required to verify our findings.

Morphological Features of the Testis among Autoimmune Mouse Model and Healthy Strains.

Autoimmune diseases play a critical role in the progression of infertility in both sexes and their severity has been reported to increase with age. However, few reports have discussed their effect on the morphological features of the testis. Therefore, we compared the morphological alterations in the testes of autoimmune model mice (MRL/MpJ-Faslpr) and the control strain (MRL/MpJ) with those of their background strain (C57BL/6N) at 3 and 6 months. Furthermore, we analyzed the changes in spermatocytes, Sertoli cells, immune cells, and Zonula occludens-1 junctional protein by immunohistochemical staining. The MRL/MpJ-Faslpr mice showed a significant increase in the serum Anti-double stranded DNA antibody level, relative spleen weight, and seminiferous luminal area when compared with other studied two strains. In contrast, a significant decrease in the relative testis weight, and numbers of both Sertoli, meiotic spermatocyte was observed in MRL/MpJ-Faslpr and MRL/MpJ mice compared with C57BL/6N mice especially at 6 months. Similarly, Zonula occludens-1 junctional protein positive cells showed a significant decrease in the same strains at 6 months. However, no immune cell infiltration could be observed among the studied three strains. Our findings suggest that the increase in autoimmune severity especially with age could lead to infertility through loss of spermatogenic and Sertoli cells, rather than the disturbance of the blood-testis barrier.

69-Year-Old Man With Nasal Congestion and Pre-Syncope

69-Year-Old Man With Nasal Congestion and Pre-Syncope

POS-170 LEISHMANIASIS COMPLICATE SYSTEMIC LUPUS ERYTHEMATOSUS: ABOUT 7 CASES

The association between leishmania (Lsc) and systemic lupus erthematosus (SLE) is rare. It is particularly serious in cases of visceral leishmania (VL). It is a parasitic infection whose hallmarks may mimic SLE symptoms especially when the two pathologies appear concomitantly. The prognosis of SLE depends on the one hand on the rapidity of diagnosis and on the other hand on the quality of treatment. The aim of this study was to analyze the characteristics of infection in leishmania in patients affected by SLE. It was a retrospective study including 07 patients hospitalized for leishmania and systemic lupus erthematosus (SLE) in the Internal Medicine Department of the Charles Nicolle hospital during the period between January 1976 and November 2020. All patients fulfilled four or more criteria defined by the American College of Rheumatology1982, revised in 1997. The diagnosis of cutaneous leishmaniasis (CL) was confirmed by a biopsy specimen. The diagnosis of VL was confirmed by the association of clinical and biology sings associated with positive bone marrow smear and/or positive serologic tests for Leishmania antibodies. Seven patients were enrolled in the study. Their mean age was 27, 85 years [14-41].There were six women and one man. The diagnosis of and SLE was concomitant in three patients, while in four cases the diagnosis of leishmania was after the diagnosis of LES. The time interval between the date of discovery of leishmaniasis and the date of confirmation of the diagnosis of SLE was 36 months[2-24]. For the diagnosis of LES, malar rash, photosensitivity, nephritis, arthralgia and positive antinuclear antibody were observed in six cases. Anti-double stranded DNA antibody was positive in two cases. For the diagnosis of CL, it was based on clinical manifestation in one case and was based in cutaneous biopsy in two cases. Five patients had nephrotic syndrom and one patient had proteinuria. Patients who had renal biopsy had active lupus nephritis class III in one case and lupus nephritis class IV in three cases. Two patients had not renal biopsy because one of them had severe hypertension and the other had severe sepsis. The diagnosis of CL was clinical in one case and histological in two cases. Clinical manifestations of VL were dominated by fever, pale mucous membranes and splenomegaly. There was pancytopenia in all patients with VL. The diagnosis of VL was confirmed by serology(n=3) andbone marrow smear (n=4). Meglumine antimonite was prescribed in the three cases of CL, in the other cases pentosan polysulfate was prescribed in a single patient while in the other two cases, they required the addition of liposomal amphotericin B. One patient was died by tamponade before treatment. Two patients were died by septic shock and only one was cured. Patients with CL had scar in two cases. The last patient died of it. The distinction between the diagnosis of SLE or its exacerbation and VL may be a clinical dilemmaresponsible for diagnostic delay. All the cases diagnosed so far have been by conventional techniques, which may underestimate the incidence of this association. The results of this study highlight a high mortality rate in cases of VL with SLE accordingly with several studies in literature.