Double-stranded DNA Antibodies Research Articles

#2889 Multiple renal tumors as an atypical clinical manifestation of granulomatosis with polyangiitis

Abstract Background and Aims Granulomatosis with polyangiitis (GPA) is a systemic small- vessel vasculitis associated with antineutrophilic cytoplasmic antibody (ANCA), in which kidney involvement often occurs. In some cases the course of vasculitis with kidney involvement is atypical, what complicates the diagnostic process and makes appropriate treatment difficult. Finding nodular masses in the kidneys always causes an oncological concern, while in the differential diagnosis a systemic vasculitis is rarely taken into account, what may lead to an unnecessary nephrectomy. Method We present a case of granulomatosis with polyangiitis (GPA) who presented with multiple tumors in the kidneys and adrenal gland. Results 29-year-old man experienced a sudden disease onset, at the age of 18 years, when due to peripheral oedema, nephrotic grade proteinuria (13.7 g/24 h), hematuria and presence of renal failure markers (serum creatinine 3.4 mg/dL), he was admitted to hospital. A suggestion of a rapidly progressive glomerulonephritis (RPGN) was put forward and a renal biopsy was performed (in the histopathological examination of the kidney, pauci-immune crescentic necrotizing glomerulonephritis was revealed). A treatment with plasmaphereses, high glucocorticosteroid doses and cyclophosphamide pulses was instituted. Haemodialysis therapy was also applied temporarily. ANCA and anti-glomerular basement membrane (GBM) antibodies were determined to give negative results. As a result of the remission-inducing treatment, an improvement of the renal function was obtained (serum creatinine 1.6-1.9 mg/dL). In spite of the remission-maintaining treatment with mycophenolate mofetil (MMF) and oral prednisone, after 10 years again a dramatic renal function impairment occurred, with a necessity of institution of a long-term haemodialysis therapy. Furthermore, on abdominal ultrasound examination multiple focal lesions were found in both kidneys, which rendered a kidney transplantation procedure in the patient impossible. In order to extend the diagnostic procedures, a magnetic resonance imaging (MRI) of the abdominal cavity without contrast agent administration was carried out (in both kidneys disseminated focal lesions were described: non-homogeneous, with moderately enhanced signal on T2-weighted images in the central part, without signs of water diffusion restriction; in the left kidney, of 23 x 22 mm and 19 x 15 mm dimensions; in the right kidney, of 30 x 32 mm, 26 x 22 mm and 22 x 18 mm dimensions. The picture of the lesions was unspecific and atypical. In the differential diagnosis granulomas could not have been ruled out, while disseminated proliferative lesions were less likely. Besides that, in both kidneys cysts of up to 7 mm diameters were present. In the lateral limb of the left adrenal gland a focal lesion was visible, of 23 x 14 mm dimensions, of a structure identical to that of the foci in both kidneys). On high-resolution computed tomography (HRCT) of the chest at the same time, small ground glass areas were found in the lungs. On positron emission tomography/computed tomography (PET/CT) no changes were visualised, suggesting presence of a metabolically active proliferative process. Tests for ANCA, antinuclear antibodies (ANA), anti- double-stranded DNA (dsDNA) antibodies, anti- GBM antibodies were again performed and gave negative results. He was diagnosed with granulomatosis with polyangiitis without ANCA and treated with corticosteroid and intravenous rituximab (4x 787 mg). Three months later, follow-up showed reduced mass lesions in the kidney and adrenal gland by MRI. Conclusion The case highlights the atypical clinical presentation of vasculitis and the significance of considering this possibility in differential diagnosis when confronting mass lesions present in the kidney.

#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.

Comparative analysis of contemporary anti-double stranded DNA antibody assays for systemic lupus erythematosus.

Elevated double-stranded DNA (dsDNA) antibody levels in blood serum are considered a disease-specific marker in systemic lupus erythematosus (SLE), correlate with disease activity and the incidence of lupus nephritis, and can be detected in up to 86% of all SLE cases. Despite the high clinical relevance, the variety of dsDNA antibody testing methods with heterogenous performance in clinical use remains challenging. This study is the first to prospectively investigate the performance of two of today's most commonly applied anti-dsDNA testing methods head-to-head under real-world conditions, as well as their correlation with other clinical and serological disease parameters in SLE patients. In this prospective study, all SLE patients undergoing treatment at the Department of Rheumatology at the University Hospital Bonn within a 13-months period (n=41) and control patients without connective-tissue disease (n=51) were consecutively enrolled and examined. For all study participants' serum samples both anti-dsDNA-NcX enzyme-linked immunoassay testing EUROIMMUN, Luebeck, Germany) and the fluorescence immunoassay ELiA dsDNA (Thermo Fisher Scientific, Waltham, USA) were performed. In addition, demographic data, further laboratory values and disease activity parameters were recorded. Clinical disease activity was assessed by SLEDAI-2K. Both assays showed high specificity (anti-dsDNA-NcX ELISA: 0.9, ELiA dsDNA: 0.959), but there were notable differences in sensitivity (anti-dsDNA-NcX ELISA: 0.51, ELiA dsDNA: 0.38). Pearsons's correlation yielded a positive correlation between anti-dsDNA concentrations and CRP concentrations for the anti-dsDNA-NcX ELISA (R=0.22; p=0.038) and a mild-to-moderate inverse correlation between concentrations of anti-dsDNA and complement C4 for the ELiA dsDNA test (R=-0.22; p=0.045) when SLE and control patients were considered together. Other than, no significant correlation between anti-dsDNA concentrations and clinical or laboratory findings was found for either test procedure. Both anti-dsDNA antibody assays represent reliable examination methods with high specificity for the diagnosis of SLE that fulfill EULAR/ACR requirements. However, the anti-dsDNA-NcX ELISA showed superior sensitivity and significant correlation with disease activity (as measured by CRP concentrations).

Successful glucocorticoid withdrawal in Chinese lupus nephritis patients: A single centre experience

ObjectiveTo evaluate the proportion of patients successfully withdrawn from glucocorticoids (GC) in a longitudinal cohort of patients with lupus nephritis over a period of 20 years, clinical and pathological predictors of patients with GC withdrawal and renal outcomes after GC withdrawal were further explored. MethodsPatients with successful GC withdrawal were identified for the cohort, and the following data were collected: demographic characteristics, clinical manifestations, pathological findings at disease onset, flares, and renal outcomes subsequent to GC withdrawal. ResultsThere were 365 patients with lupus nephritis included with a median follow-up of 109.5 (83.5,165.3) months in our cohort. A total of 21 patients (5.8 %) achieved successful GC discontinuation, with a median duration of 7.5 (3,10) years necessary for GC withdrawal. The average duration of GC reduction from 7.5 mg/d to complete withdrawal lasted for approximately 25 months (18,30). Patients in the GC-withdrawal group had a lower prevalence of nephrotic syndrome (NS) at onset (28.5 % vs. 47.3 %, P = 0.035), a higher prevalence of positive anti–double-stranded DNA (anti-dsDNA) antibody (85.7 % vs. 61.6 %, P = 0.028) and more severe endocapillary hypercellularity in the renal histopathology evaluations (3(2.5,3) vs. 3(2,3), P = 0.022). NS at disease onset was an independent risk factor to predict unachievable GC withdrawal (OR 0.296, 95 % CI (0.104,0.842), P = 0.022) by multivariate analysis. With a median follow-up of 34 (20,42) months, none of these patients had flares after GC withdrawal. ConclusionsThe discontinuation of GC therapy in LN patients with complete remission and a stable treatment regimen for at least 5 years was feasible without an increased risk of flares, ESKD or death. Low-dose GC withdrawal necessitates a prolonged duration of time and meticulous monitoring.

Antinuclear Antibodies Are Associated with an Increased Risk of Diffuse Large B-Cell Lymphoma.

Immune dysregulation is thought to increase the risk of non-Hodgkin lymphoma (NHL), but the evidence varies by subtype. We evaluated whether antinuclear antibodies (ANA), double-stranded DNA antibodies (anti-dsDNA), and extractable nuclear antigen antibodies (anti-ENA) were associated with the risk of common NHL subtypes in a nested case-control study. The autoantibodies were tested in serum collected years prior to NHL diagnosis in 832 cases and 809 controls from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Logistic regression was used to determine odds ratios (ORs) and 95% confidence intervals (95% CI) for the association with NHL risk. No association was observed between ANA positivity and NHL risk overall (OR: 1.18, 95% CI: 0.88-1.58); however, ANA positivity was associated with an increased risk of diffuse large B-cell lymphoma (DLBCL) (OR: 1.83, 95% CI: 1.15-2.91), with 19.7% of cases and 12.2% of controls testing positive. The presence of either anti-ENA or anti-dsDNA was associated with an increased risk of NHL (OR: 2.93, 95% CI: 1.18-7.28), particularly DLBCL (OR: 3.51, 95% CI: 1.02-12.0) and marginal zone lymphoma (OR: 8.86, 95% CI: 1.26-62.0). Our study demonstrates that autoantibodies are associated with an elevated risk of DLBCL, providing support for autoimmunity as a risk factor.

E58 The rheumatologic masquerader: a case report on SLE-dermatomyositis-systemic scleroderma overlap syndrome

Abstract Introduction Juvenile dermatomyositis is an autoimmune connective tissue disorder characterized by idiopathic inflammatory myopathy primarily affecting the skin and muscles(1, 2). It may occur alone or in overlap syndromes usually with systemic scleroderma, systemic lupus erythematosus (SLE) and mixed connective tissue disease(3, 4). There is need to further describe and characterize cases encountered in different set ups. Objective To describe a case of dermatomyositis-scleroderma overlap in an African male adolescent. Methods We carried out a retrospective chart review to ascertain clinical features and management strategies. Results We present a case of a 17- year old African male patient who presented with a diagnosis of systemic lupus erythematosus made at a peripheral facility in February 2021, and started on azathioprine 50 mg daily, hydroxychloroquine 200 mg daily and prednisolone 5 mg twice daily. He presented on 30th November 2022 with a 2-year history of bilateral elbow, knee, ankle pain and swelling with an 8-month history of bilateral proximal upper and lower limb muscle weakness. Review of systems revealed alopecia, occasional fever and hyperpigmentation over his proximal interphalangeal and metacarpophalangeal joints that has since evolved to hypopigmentation. Positive examination findings included fine sparse hair, heliotrope rash, Gottron's papule, salt and pepper skin rash, hardening of the skin over the arm and thighs with a rodnan score 3/3 over the phalanges, nodular non tender lesions in the abdominal subcutaneous tissue and dactylitis with fixed flexion deformities of both elbows. He had bilateral flexion contractures of both elbows and knees with dactylitic fingers. Laboratory investigations showed an elevated CRP 94 mg/l, elevated lactate dehydrogenase 458 U/l, elevated creatine kinase 492U/l, positive antinuclear antibodies (1:640 titres) with a nuclear coarse and large speckled pattern, positive double stranded DNA antibodies and weak positive anti SM, anti RNP and PCNA antibodies. Myositis panel was positive for MDA5 and OJ. Pelvic MRI showed features of proximal inflammatory myositis. The childhood myositis assessment scale revealed a score of 25/52. ECHO and chest radiograph were normal. Pulmonary function test showed a low FEV 1 and FVC in keeping with a restrictive lung picture. Gastroenterology review revealed gastritis with no other stigmata of autoimmune disease. Management has consisted of monthly therapy with intravenous immunoglobulin. Azathioprine therapy was switched with mycophenolate mofetil 1 gram twelve hourly. He was advised on sunscreen protection. Physiotherapy and occupational therapy has been ongoing. Three months of follow up has led to the resolution of the flexion knee contractures, improved functionality in activities of daily living and a rodnan score of 2/3 over the phalanges. Conclusion SLE-juvenile dermatomyositis and systemic scleroderma can occur as an overlap syndrome and a definitive diagnosis remains elusive to many clinicians. A thorough history and comprehensive physical examination remains key to establishing a correct diagnosis. Early patient referral to paediatric rheumatologist for prompt appropriate treatment can avert debilitating morbidity and mortality.

Two-carba cyclic phosphatidic acid treatment promotes phenotypic switch from M1 to M2 microglia and prevents behavioral abnormalities in a mouse model of neuropsychiatric systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease associated with the production of double-stranded DNA (dsDNA) antibodies and other antibodies that predominantly affects women with a wide range of lesions. Although neuropsychiatric lupus erythematosus (NPSLE), characterized by neuropsychiatric symptoms related to cerebrovascular diseases or depression, ranks high in severity, no specific treatment has been defined. Two-carba cyclic phosphatidic acid (2ccPA), a derivative of cyclic phosphatidic acid, was isolated from the true slime mold Physarum polycephalum in 1992. 2ccPA treatment suppresses neuroinflammation and promotes tissue repair in mouse multiple sclerosis and traumatic brain injury models. In this study, we performed behavioral tests on MRL/lpr mice as an NPSLE model. MRL/lpr mice showed increased depression-like behaviors compared with control mice, which were significantly suppressed by 2ccPA treatment. The expression of CD68, an M1 phenotypic marker of microglia, was significantly elevated in the prefrontal cortex and hippocampus of MRL/lpr mice, which was significantly suppressed by 2ccPA treatment. In contrast, the expression of Arginase1, an M2 phenotypic marker of microglia, was significantly increased by 2ccPA treatment. Compared to control mice, MRL/lpr mice showed higher plasma levels of anti-dsDNA antibodies, which are mainly involved in SLE pathogenesis. 2ccPA treatment decreased these levels in the MRL/lpr mice. These results suggest that 2ccPA treatment suppresses behavioral abnormalities by promoting a microglial phenotypic switch from M1 to M2 in MRL/lpr mice.

Toll-like receptor-7 gene polymorphism at 3− UTR (rs3853839) in relation to Systemic Lupus Erythematosus pathogenesis in Iraqi patients

The role of Toll-like receptor-7 (TLR-7) gene polymorphism in the pathogenesis of autoimmune diseases like Systemic Lupus Erythematosus (SLE) is highlighted in the last decade. This study aims to investigate the role of 3− UTR of TLR-7 gene polymorphism (rs3853839) in the pathogenesis of SLE in the Iraqi population. The SLE patients were diagnosed based on clinical and laboratory criteria like symptoms, antinuclear antibodies (ANA), anti-dsDNA antibodies and Toll-like receptor-7 (TLR-7). The 3− UTR of TLR-7 gene polymorphism (rs3853839) genotyping was determined by sequencing of TLR-7 PCR product. The serum ANA, dsDNA and TLR-7 of SLE patients was significantly increased (3.86 ± 0.26 U/ml, p=0.01, 3.54 ± 0.21 U/ml, p=0.01 and 28.46 ng/ml, p=0.01 respectively). The increased antinuclear antibodies (AUC: 1.00, cut-off value ≥1.782 U/ml, had 100 % sensitivity and 100 % specificity) and double-strand DNA antibodies (AUC: 1.00, cut-off value ≥ 1.706 U/ml, had 100 % sensitivity and 100 % specificity) is the highest discriminative parameters associated with systemic lupus erythematosus development. TLR-7 (AUC: 0.882, cut-off value ≥23.778 ng/ml, had 92 % sensitivity and 82 % specificity) was less associated with SLE development. The GG genotype is significantly occurring in SLE patients (23.3%, OR: 2.154, 95%CI: 0.356–13.049, P = 0.04). While CG genotype significantly occurred in the control groups (66.6 %, OR: 0.308, 95%CI: 0.0962–0.984, p = 0.046). In conclusion, the TLR-7 rs3853839 GG genotype is associated with SLE pathogenesis in Iraqi SLE patients while the TLR-7 rs3853839 CG genotype is common in SLE free control.

#2733 TRANSPLANTATION OF MESENCHYMAL STEM CELLS - NEW FOCUS OF IMMUNE CORRECTION IN TREATMENT OF LUPUS NEPHRITIS

Abstract Background and Aims Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterised by the production of organ-specific autoantibodies to components of cell nucleus, immune complex lesions of the connective tissue, and the development of irreversible damage of internal organs. Chronic relapsing course of SLE, resistance to steroid and immunosuppressive therapy, toxic effects of drugs determine the need of search for new therapeutic approaches. Objective To evaluate the efficacy and safety of bone marrow mesenchymal stem cell (MSC) transplantation with high-dose immunosuppressive therapy (HIST) in SLE patients. Method A total amount of 15 patients with a diagnosis of SLE (ACR criteria) refractory to classical immunosuppressive therapy was examined. Patients were divided into 2 groups: patients from the main group underwent MSCs transplantation with HIST (n = 10), while the control group was observed on the background of traditional immunosuppressive therapy without cell transplantation (n = 5). Both groups were comparable in age, gender of patients, duration and severity of the disease. The SELENA-SLEDAI was used to determine SLE activity. Cytokines were examined by ELISA (IL-1Β, IL-4, IL-10, TNF-Α), antibodies to double-stranded DNA (anti-dsDNA) and anti-nuclear antibodies (ANA) by indirect immunofluorescence. Morphological examination of kidney included Masson-trichrome histochemistry for collagen fibers, silvering reaction for elastic and reticulin fibers, immunofluorescent and immunohistochemical methods. The safety assessment included registration of various adverse events during and after transplantation. Statistical analysis was carried out by Kruskal-Wallis test using STATISTICA 6.1. Results Monitoring the effectiveness of autologous stem cell transplantation in SLE patients showed a significant 2-fold decrease in activity by SELENA-SLEDAI score from 14.67±1.15 to 7.33±1.15 points after 12 months (p = 0.03). In the control group, this indicator remained unchanged and amounted to 15.0±0.87 points despite ongoing immunosuppressive therapy. Clinical efficacy was noted in all patients receiving HIST and MSC transplantation, which was confirmed by a significant decrease in daily proteinuria from 2,48±0,77 to 1,06±0,56 g/l, a decrease in the value of antibodies to DNA (from 443,28±547,53 to 187,8±146,60) and blood cytokines (significantly for TNF-Α), and an increase in the level of complement (though insignificantly). According to kidney biopsy data, after MSC transplantation with HIST, positive dynamics consisted in an increase in the number of reticulin fibers in the vascular loops of the glomeruli, as well as a decrease in the immune inflammatory process in the vascular loops of the glomeruli by immunofluorescence analysis for the spectrum of antibodies (Figure 1). In most patients of the main group, the doses of methylprednisolone and immune suppressants were reduced. Chills during transplantation was registered in one patient; no other unwanted adverse events were identified. Conclusion MSC transplantation in combination with HIST is significantly more effective than traditional immunosuppressive therapy in SLE according to clinical and laboratory data. The method is safe, allows decreasing signs of autoimmune aggression and can be used in cases of refractoriness, low efficiency or intolerance of standard therapy for SLE.

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...

Case report: disease mechanisms and medical management of calcium nephrolithiasis in rheumatologic diseases

BackgroundNephrolithiasis as a feature of rheumatologic diseases is under recognized. Understanding presenting features, diagnostic testing is crucial to proper management.Case presentationA 32 year old woman with a history of recurrent complicated nephrolithiasis presented to a rheumatologist for a several month history of fatigue, dry eyes, dry mouth, arthralgias. She had a positive double-stranded DNA, positive SSA and SSB antibodies. She was diagnosed with Systemic Lupus erythematosus (SLE) and Sjogren's syndrome and was started on mycophenalate mofetil. Of relevance was a visit to her local emergency room 4 years earlier with profound weakness with unexplained marked hypokalemia and a non-anion gap metabolic acidosis. Approximately one year after that episode she developed flank pain and nephrocalcinosis. She had multiple issues over the ensuing years with stones and infections on both sides. Interventions included extracorporeal shockwave lithotripsy as well as open lithotomy and eventual auto-transplantation of left kidney for recurrent ureteric stenosis. 24 h stone profile revealed marked hypocitraturia, normal urine calcium, normal urine oxalate and uric acid. She was treated with potassium citrate. Mycophenolate was eventually stopped due to recurrent urinary tract infections and she was started on Belimumab. Because of recurrent SLE flares, treatment was changed to Rituximab (every 6 months) with clinical and serologic improvement. Her kidney stone frequency gradually improved and no further interventions needed although she continued to require citrate repletion for hypocitraturia.ConclusionsNephrolithiasis can be a prominent and even presenting feature in Sjogrens syndrome as well as other rheumatologic diseases. Prompt recognition and understanding disease mechanisms is important for best therapeutic interventions for kidney stone prevention as well as treatment of underlying bone mineral disease.

Bilateral Facial Nerve Palsy as a Rare Presentation of Systemic Lupus Erythematosus

Abstract Systemic lupus erythematosus (SLE), a disease of the immune system, has a relapsing-remitting course. It is known to affect multiple organ systems of the body, including the nervous system. Cranial neuropathy, particularly facial neuropathy, is an unusual complication of SLE whose pathogenic mechanism is still not understood. Cardiac involvement, like myocarditis and papilledema, is another rare presentation of SLE. A 23-year-old male had bilateral lower motor neuron type of facial palsy which on a thorough investigation was found to be as a manifestation of SLE confirmed by antinuclear antibodies and double-stranded DNA antibody positive test. Electrocardiogram and echocardiography were suggestive of myocarditis. Fundus examination revealed Grade 2 papilledema. The patient was managed with symptomatic treatment along with corticosteroids, to which he responded gradually. Bilateral facial nerve lower motor neuron type palsy is a rare manifestation of SLE which should be diagnosed promptly and can be managed with corticosteroids. The clinician should also keep an eye on infrequent manifestations like myocarditis and papilledema.

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 & 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

Diffuse Alveolar Hemorrhage: A Rare Underlying Disease in a Child with Chronic Respiratory Symptoms

Background: Diffuse lung disease (DLD), conventionally known as interstitial lung disease (ILD), encompasses a spectrum of diseases involving the pulmonary parenchyma with impairment of gaseous exchange. Most of the diseases under DLD have similar presentations, but appropriate investigations can delineate the exact disease. Diffuse alveolar hemorrhage (DAH) is one of the diseases under this umbrella group of DLD. Clinical Description: A 3-year-old girl suffering from persistent breathlessness and intermittent hypoxic exacerbations over 1 year, presented to us with acute respiratory worsening. She was underweight with stunting and had severe pallor. She had received blood transfusions in previous hospitalizations. Chest-X-ray shows reticular opacities, with High Resolution Computed Tomography (HRCT) chest showing bilateral diffuse ground glass opacities involving all lobes with the prominent pulmonary artery. The broncho-alveolar lavage showed hemosiderin-laden macrophages, thereby confirming alveolar hemorrhage. Antinuclear antibody was positive, though double-stranded DNA and Anti-neutrophil cytoplasmic antibody were negative. The child was thus diagnosed with a case of DAH, probably, immune mediated. Management: The child was treated with supportive care, including oxygen, intravenous fluids, antibiotics, and packed red cell transfusion. Even after improvement in hemoglobin, oxygen dependency persisted. The child was then administered Intravenous Immunoglobulin and prednisolone, to which the child showed a response with gradual weaning off oxygen. Conclusions: In any child presenting with persistent respiratory symptoms, especially exercise intolerance, over a prolonged period with intermittent hypoxic exacerbations, a pediatrician should consider diagnoses beyond infections and multitrigger wheezing. Such manifestations, particularly if associated with failure to thrive, may be due to DLD. DAH, a rare form of DLD, may be a possibility in such children.

Predictors of overlapping autoimmune disease in Neuromyelitis Optica Spectrum disorder (NMOSD): A retrospective analysis in two inner-city hospitals.

BackgroundThe coexistence of Neuromyelitis Optica spectrum disorder (NMOSD) with other autoimmune diseases (AD-NMOSD) presents worse clinical outcomes and healthcare costs than NMOSD alone (NMOSD-only). NMOSD and other autoimmune diseases also have a higher prevalence and morbidity in Black. We aim to compare clinical features and treatment responses in NMOSD patients with and without overlapping autoimmunity in a predominantly Black cohort. We further identify predictors associated with each clinical subtype. MethodsAD-NMOSD (n = 14) and NMOSD-only (n = 27) patients were identified retrospectively. Demographic, clinical, laboratory, imaging, and response to treatment data were examined. ResultsOur cohort was predominately Black (82.9%). The prevalence of grouped-comorbidities, history of infections, sensory symptoms, Expanded Disability Status Scale (EDSS) before treatment, double-stranded DNA, antinuclear, ribonucleoprotein, and antiphospholipid antibodies, spinal-cord edema, white matter occipital lesions, and the levels of C-reactive protein, urine protein/creatinine, white blood cell count in cerebrospinal fluid (CSF), were higher in AD-NMOSD patients (p < 0.05 and/or Cramer's V > 30, Cohen's d > 50), whereas the age of males, visual symptoms, serum albumin, platelet count, and optic nerve enhancement were lower. EDSS after treatment improved in both groups being more evident in NMOSD-only patients (p = 0.003, SE = 0.58 vs p = 0.075, SE = 0.51). Other variables had a close to moderate SE, and others did not differ between NMOSD subtypes. A higher frequency of grouped-comorbidities, lower serum albumin, and platelet count were independently associated with a higher risk for AD-NMOSD. ConclusionsSome clinical features between AD-NMOSD and NMOSD-only patients were similar, while others differed. Comorbidities, serum albumin, and platelet count may be independent predictors of AD-NMOSD.

CYSTIC LUNG DISEASE IN A YOUNG MALE WITH SYSTEMIC LUPUS ERYTHEMATOSUS

CYSTIC LUNG DISEASE IN A YOUNG MALE WITH SYSTEMIC LUPUS ERYTHEMATOSUS

P13 A case of Kikuchi-Fujimoto disease triggered by an episode of bacterial cellulitis, associated with features of SLE

P13 A case of Kikuchi-Fujimoto disease triggered by an episode of bacterial cellulitis, associated with features of SLE

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

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

Plasma Kidney Injury Molecule-1 in Systemic Lupus Erythematosus: Discordance Between ELISA and Proximity Extension Assay

Oligonucleotide-labeled antibodies (Olink, Olink Proteomics) and aptamers (SomaScan, SomaLogic) are increasingly used in biomarker discovery and research. However, few studies have compared the protein levels measured on proteomics platforms with those measured using conventional immunoaffinity assays.1-5 This may be especially relevant in the setting of autoimmune diseases, such as systemic lupus erythematosus (SLE), where anti–double-stranded DNA (anti-dsDNA) antibodies could interfere with immunoassay technologies that use oligonucleotide-based antibodies (Olink) or aptamers (SomaScan).

Interpreting Rheumatology Laboratory Tests

Interpreting Rheumatology Laboratory Tests