Antinuclear Antibodies Antibodies Research Articles

#2600 Idiopathic full-house non-lupus nephropathy

Abstract Background and Aims A full-house pattern at immunofluorescence (IF) in kidney biopsies is usually associated with Lupus Nephritis (LN). However, it can be also secondary to other causes, such as infections, or it can idiopathic, without a defined origin. Idiopathic Full House non-lupus Nephropathy (iFH-N) represents a rare entity previously identified in small cohorts of patients, with different clinical features and outcomes. A limited number of the described cases developed overt systemic lupus erythematosus (SLE) during follow up, while renal outcome varied across different studies. A retrospective observational study aimed at evaluating clinical presentation and outcomes of patients with iFH-N in a Tertiary Center has been performed. Long-term renal function and development of overt SLE have been considered as main outcomes of the study. Method All native kidney biopsies performed from January 2012 to December 2022 in our Institution were considered. Full-house pattern was defined as simultaneous positivity for IgG, IgM, IgA, C3 and C1q staining at IF. Inclusion criteria were: age ≥18, full-house pattern at kidney biopsy, patients not meeting criteria for SLE diagnosis according to American College of Rheumatology (ACR) 1997 classification or Systemic Lupus International Collaborating Clinics (SLICC) 2012 criteria. Exclusion criteria: diagnosis of SLE, secondary causes of full-house pattern at kidney biopsy. We considered histological, clinical and laboratory features, performed therapies, renal function and SLE development during follow up. Results In the considered period, 2110 patients underwent a native kidney biopsy at our Institution. Of these, 91 patients had a histological finding of full-house nephropathy and were initially included for further evaluation. Of the 91 patients, 84 had received a diagnosis of SLE and were excluded, while 7 did not meet the criteria for a diagnosis of SLE. Two of these 7 were further excluded, having a full house pattern secondary to other conditions. Five patients were finally labelled as iFH-N. At kidney biopsy, all 5 included subjects had a Membranous Nephropathy, with extracapillary proliferation in 2 cases. They were all females, 4 Caucasians (80%), 1 Black (20%). At presentation, mean age was 28.2 years (range 21–40). All had impairment of kidney function, 2 of 5 had a full-blown nephrotic syndrome, 3 of 5 a nephrotic range proteinuria. Mean serum creatinine was 2.1 mg/dl (SD± 0.47), mean eGFR 35.2 ml/min/1.73 m2 (SD ±11), mean proteinuria 7.1 gr/24 h (SD ±3.3). Antinuclear antibodies (ANA) were negative in 4 of 5 patients; anti-dsDNA, anti-extractable nuclear antigens (ENAs) and antiphospholipid antibodies were negative in all subjects; slightly low C3 was present in 3 of 5 subjects. All patients received immunosuppressive therapy, including high dose intravenous (iv) steroids in association with cyclophosphamide (CYC) or mycophenolate mofetil, or Intensified B Cell Depletion Protocol (i.e. iv steroids + CYC and Rituximab). Mean follow-up from the time of kidney biopsy was 7.4 year (SD ± 2.4) (range 3–10 years). During follow up, 4 patients (80%) developed end stage renal disease (ESRD) needing renal replacement therapy, 3 of them within 24 months after presentation. The two patients with crescents had a severe prognosis, starting dialysis within 10 months after presentation. The fifth patient developed chronic kidney disease stage 4. One patient formally developed an ACR negative, SLICC positive SLE two years after presentation, with new positivity for ANA and anti-dsDNA antibodies at high titer and low C3, in addition to renal involvement. Conclusion All patients with iFH-N had similar presentation, being all young females, with a Membranous Nephropathy, nephrotic proteinuria and impairment of kidney function. They all had an aggressive form of kidney disease, refractory to different regimens of immunosuppression and with poor long-term renal outcome. Only one case developed SLE on the long term, although without systemic signs. The relationship between idiopathic full-house nephropathy and SLE remains controversial.

P022 Unmasking the storm: hemophagocytic lymphohistiocytosis in systemic lupus erythematosus - a case series

Abstract Background/Aims Hemophagocytic lymphohistiocytosis (HLH), a critical illness of uncontrolled immunological activity and hyperinflammation, manifests as primary/familial or secondary form. Secondary HLH can be of multi-faceted etiology including infections, cancer, autoimmune and immunodeficiencies. HLH in context of systemic lupus erythematosus (SLE) is a rare entity and mirrors the clinical picture of SLE flare, adding to the diagnostic dilemma. Methods Our objective is to consider HLH as a key differential in unidentified autoimmune diseases. We present a trio of cases of undiagnosed SLE manifesting as HLH. Results A 13-year-old male presented with fever, rash, oral ulcers, and jaundice for a month with passage of dark coloured urine for last seven days. On examination, he had generalized lymphadenopathy, erythematous maculopapular rashes, palpable purpura, non-scarring alopecia, and hepatosplenomegaly. The labs revealed pancytopenia (Hb 9.8g/dL, WBC 2000/mm3, Platelets 23000/mm3), deranged creatinine (1.6mg/dL), transaminitis and hyperbilirubinemia, hyper-ferritinemia (2420µg/dL), hypertriglyceridemia (280mg/dL), hypofibrinogenemia (142mg/dL), and nephrotic range proteinuria (3.7g/24h). Diagnosis of SLE was confirmed by high titres of antinuclear antibody (ANA) and anti-double stranded DNA (dsDNA) and anti-Smith positivity. Renal biopsy showed class II lupus nephritis and acute tubular necrosis. Bone marrow biopsy revealed hemophagocytosis and the diagnosis of SLE complicated by HLH was made. A 16-year-old girl presented with fever and headache for three weeks, worsening over last ten days with irritable behaviour for one day, and respiratory distress that necessitated endotracheal intubation. The presence of pancytopenia (9.1/1940/41000), transamintis, hyper-ferritinemia (4040µg/dL), hypertriglyceridemia (250mg/dL), and low fibrinogen (133mg/dL) in laboratory evaluation raised a compelling suspicion of HLH confirmed by hemophagocytosis on marrow biopsy. Cerebrospinal fluid analysis was unremarkable, however MRI detected features of vasculitis with vasculitic infarcts. Direct Coomb’s test was positive. Autoimmune profiling unveiled positive results for ANA, anti-dsDNA, and anti-Smith antibodies consistent with SLE. A 21-year-old female presented with fever and arthralgias for two months. Investigations were suggestive of pancytopenia (7/1050/36000), raised ESR (126mm/hr) and CRP (54 mg/dL), elevated ferritin (4320 µg/dL), lactate dehydrogenase (1068U/L) and triglycerides (439mg/dL). The marrow biopsy was negative for hemophagocytosis while her soluble interleukin - 2 receptor levels were elevated (2740 U/ml). ANA and dsDNA were positive in significant titres, complement levels were low and Coombs test was positive, thereby confirming the primary diagnosis of SLE. All patients received methylprednisolone pulse along with cyclophosphamide in case 1 and IVIG in case 2 and 3, resulting in remarkable improvement. Conclusion With a prevalence of 0.9-4.6%, HLH secondary to SLE is an uncommon entity. The diagnosis of HLH related to SLE is challenging since the symptoms overlap, however findings of hyperferritinemia, hypofibrinogenemia, and hypertriglyceridemia favour HLH over SLE. Once HLH is proven, immunological testing for SLE is warranted to prevent diagnostic delay. Early treatment is needed to combat such a fulminant life-threatening illness. Disclosure R. Mishra: None. A. Rohatgi: None. S. Anuradha: None. N. Kumar: None. S. Singhla: None. S.T. Mathews: None. S. Kumar: None. P. Gautam: None.

Clinical and Biological Lupus Induced by Infliximab in Crohn's Disease

The use of anti-TNFs in Crohn's disease (CD) is often associated with the appearance of antinuclear antibodies, and more rarely with anti-native DNA antibodies. Anti-TNF-induced lupus remains exceptional. We report the case of a 52-year-old woman, followed for colonic Crohn's disease, treated with Infliximab. After 12 months of treatment with anti-TNF alpha (Infliximab), the patient developed clinical and biological lupus with positive antinuclear antibodies (ANA) and anti-native DNA antibodies (IgG). Infliximab treatment was discontinued. Six months after stopping the treatment, the patient had no recurrence of clinical signs, and immunological examinations showed a marked decrease in total ANA and anti-native DNA antibodies (IgG).

Mild-to-moderate COVID-19 does not predispose to the development of autoimmune rheumatic diseases or autoimmune-based thrombosis.

An infection with severe acute respiratory syndrome coronavirus (SARS-CoV-2) may have a significant impact on the human immune system. Interactions between the virus and defence mechanisms may promote the development of autoimmune processes which manifest as antinuclear antibody (ANA) synthesis. Since many different viruses are suspected to take part in the pathogenesis of different systemic autoimmune rheumatic diseases (SARDs), we examined whether coronavirus disease 2019 convalescents who suffer from mild to moderate disease have a higher risk of developing ANA and anti-β2-glicoprotein I IgG antibodies (β2 GPI). In a retrospective study, we examined 294 adults among volunteer blood donors divided into convalescents (N = 215) and healthy controls (N = 79). For ANA detection, we used line-blotting, a type of indirect immunofluorescence assay (IF), to determine antigenic specificity and ELISA for β2 GPI. We found a lower incidence of ANA in convalescents than in healthy controls, with the majority of these antibodies directed to antigens with no known clinical significance. Additionally, no participants were positive for β2 GPI in either group. Our results show that COVID-19 with mild to moderate symptoms in the generally healthy population does not induce the development of ANA or anti-β2 GPI antibodies for at least 6 months following the disease.

Laboratory risk factors for coexistent primary biliary cholangitis in patients with Sjögren’s syndrome: a retrospective study

BackgroundLimited research exists on the laboratory characteristics of coexistent primary biliary cholangitis (PBC) and Sjögren’s syndrome (SS). This study aimed to investigate the laboratory risk factors for the coexistence of PBC in patients with SS.MethodsEighty-two patients with coexistent SS and PBC (median age 52.50 years) and 82 age- and sex-matched SS controls were retrospectively enrolled between July 2015 and July 2021. The clinical and laboratory characteristics of the two groups were compared. Laboratory risk factors for the coexistence of PBC in patients with SS were analyzed using logistic regression analysis.ResultsBoth groups had a similar prevalence of hypertension, diabetes, thyroid disease, and interstitial lung disease. Compared with the SS group, patients in the SS + PBC group had higher levels of liver enzymes, immunoglobulins M (IgM), G2, and G3 (P < 0.05). The percentage of patients with an antinuclear antibody (ANA) titre > 1:10000 in the SS + PBC group was 56.1%, higher than that in the SS group (19.5%, P < 0.05). Additionally, cytoplasmic, centromeric, and nuclear membranous patterns of ANA and positive anti-centromere antibody (ACA) were observed more frequently in the SS + PBC group (P < 0.05). Logistic regression analysis showed that elevated IgM levels, high ANA titre, cytoplasmic pattern, and ACA were independent risk factors for PBC coexistence in SS.ConclusionsIn addition to established risk factors, elevated IgM levels, positive ACA, and high ANA titre with cytoplasmic pattern provide clues to clinicians for the early screening and diagnosis of PBC in patients with SS.

The frequency of co-positivity of anti-smooth muscle antibody and anti-nuclear antibodies and their contribution to the diagnosis of autoimmune hepatitis

Aim: Autoimmune hepatitis (AIH) is a chronic disease observed especially in women. The International Autoimmune Hepatitis Group recommends scoring systems for diagnosis using clinical and laboratory data. All scoring systems gave points to autoantibodies as anti-nuclear antibody (ANA) and anti-smooth muscle antibody (SMA) positivity. This study investigates the impact of the co-positivity of the ANA and SMA antibodies on the autoimmune hepatitis diagnosis.&#x0D; Material and Method: We monitored 78 autoimmune liver disease (autoimmune hepatitis, AIH) suspected patients with positive SMA antibody and then further tested for ANA between 2014 and2021. SMA test was screened at 1/40 and 1/100 titers and patients who were positive were taken to further dilution. The ANA test was screened at a titer of 1/40 and 1/160, a positive result was found to be repeated with advanced dilutions. All patients’ autoantibody scores of simplified AIH diagnostic system were calculated.&#x0D; Results: Seventy eight patients with positive SMA antibodies screened for ANA test with 1/40 and 1/160 titer, only 2 patients was found to be negative. The most frequently observed ANA pattern is cytoplasmic linear fibrils (68% ). The 95% ANA positive results was examined at a screening titer of 1/160. The 95% SMA positive results was found at a screening titer of 1/100. The autoantibody scores of 76 patients were +2, patient’s scores were +1.&#x0D; Conclusion: SMA antibody positivity is accompanied by a high rate of ANA antibody positivity but the co-positivity didn’t effect diagnostic score systems. On the other the co-positivity could be a sign of another associated autoimmune diseases.

Relations between antinuclear, antineutrophil cytoplasmic, anticardiolipin antibodies and degree of neurological deficit, cerebrovascular stenosis in cerebral infarction patients.

To investigate the correlation of antinuclear antibody (ANA), antineutrophil cytoplasmic antibody (ANCA) and anticardiolipin antibody (ACA) with the degree of the neurological defect and cerebrovascular stenosis in patients with cerebral infarction. Clinical data of 99 patients with acute cerebral infarction (ACI) admitted to the Department of Neurology of Baoding First Central Hospital from June 2020 to December 2021 were retrospectively analyzed, and their ANA, ACA, ANCA, neurological deficit (NIHSS) scores as well as cerebrovascular stenosis were detected and assessed. Moreover, the correlation between the positive expression rates of ANA, ANCA, ACA and the degree of the neurological deficit, as well as the location and degree of cerebrovascular stenosis, were analyzed. All patients had ANA, ACA, ANCA antibodies with positive rates of 68.69%, 70.71%, 69.70%, and mild, moderate, and severe cerebrovascular stenosis with incidence rates of 28.28%, 32.32%, and 39.39% respectively; Moreover, their incidence of mild, moderate, and severe neurological deficits were 15.15%, 44.44%, and 40.40%, respectively. Statistically significant differences could be observed in the degree of cerebrovascular stenosis and neurological deficit between the ANA, ACA and ANCA antibody positive group and the negative group (p<0.05). ANA, ACA, ANCA antibody positive was moderately positively correlated with cerebrovascular stenosis rate and NIHSS score (0.40<r<0.60, p<0.05). The positive rates of ANA, ACA and ANCA antibodies were higher in patients with ACI, which was closely correlated with the degree of cerebrovascular stenosis and neurological deficit.

The Risk of Autoimmunity Development following mRNA COVID-19 Vaccination.

The broad spectrum of interactions between autoimmune diseases and the SARS-CoV-2 vaccination is not fully understood. This study aims to evaluate the prevalence of anti-nuclear antibodies (ANA), anti-ENA, anticardiolipin antibodies (ACL), and anti-beta-2 glycoprotein I antibodies (anti-β2GPI) before and after the SARS-CoV-2 mRNA vaccination in a real-life setting in healthcare professionals. The identification of risk factors associated with vaccine immunogenicity was evaluated. The study group consisted of employees of two hospitals (354 individuals). Samples for antibody assays were collected before vaccination and at 7-9 months after complete immunisation. There was no significant increase in the prevalence of ANA, ACL or anti-β2GPI antibodies, or autoimmune diseases in subjects who were vaccinated 7-9 months after complete immunisation. In terms of detected anti-ENA, the anti-DFS70 antibodies were found in 6 times more subjects than before vaccination at the second blood draw (in 18 and 3 subjects, respectively) (p = 0.001). There were no significant relationships between a SARS-CoV-2 infection history, humoral response, cellular response, subject category, smoking, sex, body weight, ANA, anti-ENA, ACL, or anti-β2GPI. This study revealed a possible association between the severity of vaccine adverse events (VAEs) and ANA titre. Individuals with more severe VAEs (&gt;10 points) after the second dose of the vaccine had significantly higher ANA titre after complete immunization. When analysing the significance of time between the ANA, anti-ENA, ACL, and anti- β2GPI assays and complete immunisation antibody values, no qualitative result was statistically significant. There was correlation between the time since complete immunization and ANA after.

Prevalence of Antineutrophil Cytoplasmic Antibodies and Antinuclear Antibodies in Patients with Pulmonary Tuberculosis: A Tertiary Care Center Experience from North India.

Tuberculosis (TB) can have manifestations closely mimicking autoimmune diseases. The prevalence of autoantibodies in TB varies among different populations. To study the prevalence of anti-neutrophilic cytoplasmic antibodies (ANCA) and antinuclear antibodies (ANA) in pulmonary tuberculosis (PTB). This was a cross-sectional, observational study. Subjects with microbiologically confirmed PTB, either via smear or culture positivity on sputum or bronchoalveolar lavage (BAL) fluid, or positive rapid diagnostic tests were included. ANCA against proteinase-3 (PR3), myeloperoxidase (MPO), lactoferrin, and elastase were tested using an enzyme-linked immunosorbent assay (ELISA). ANA was detected using indirect immunofluorescence (IIF). Eighty-nine subjects with a median [interquartile range (IQR)] age of 28 (20-46) years, 67.4% males, were recruited. Eighty-one subjects had microbiological confirmation on sputum examination, and eight required examination of BAL fluid. Sera were drawn from 62 treatment-naïve subjects, the rest (27) were on antitubercular therapy (ATT). Eighty-six (96.6%) subjects tested positive for anti-elastase antibody, seven of which were also positive for anti-PR3. None were positive for anti-MPO and anti-lactoferrin. Six (6.7%) subjects tested positive for ANA. None of the subjects had features of underlying connective tissue disease or vasculitis. PTB patients showed a high prevalence of anti-elastase and a low prevalence of ANA and anti-PR3 antibodies. ANCA positivity should be interpreted with caution in TB endemic areas. The role of anti-elastase antibodies in differentiating TB from ANCA-associated vasculitis (AAV) needs further research.

Clinical and prognostic significance of antinuclear antibodies in primary antiphospholipid syndrome: A multicenter retrospective study.

The antiphospholipid syndrome (APS) (1) is defined by the development of vascular thrombosis, or pregnancy morbidity in the presence of persistent antiphospholipid antibodies (aPL). Antinuclear antibodies (ANA) can be detected in primary APS patients without any clinical systemic autoimmune disease. The presence of ANA antibodies could confer a specific phenotype in primary APS. To evaluate the characteristics of APS patients with antinuclear antibodies without other autoimmune disease (ANA positive APS patients) in comparison with primary APS without ANA or secondary APS patients with associated systemic lupus erythematosus (SLE). Clinical and biologic data from 195 APS were retrospectively collected and patients were classified as primary APS with positive ANA (ANA-positive APS), primary APS without any ANA (ANA-negative APS), and SLE-associated APS (SLE-APS). Fourty patients (21%) were classified into ANA-positive APS group, 77 (39%) in ANA-negative APS and 78 (40%) in SLE-APS. In ANA-positive APS patients, 20 patients (51%) had arterial thrombosis, 14 (41%) had veinous thrombosis and 19% had obstetrical complications. There was no difference between the three groups for the frequency of thrombotic manifestations and obstetrical complications. ANA-positive APS patients had more non-criteria manifestations than ANA-negative APS (48% versus 25%; P≤0.01). ANA-positive APS had more triple aPL positivity (59% versus 18%; P<0.001) and more thrombosis and obstetrical recurrences (63% versus 36%; P<0.01) in comparison with ANA-negative APS patients. ANA-positive APS had more triple aPL positivity than SLE-APS patients (54% versus 33%; P<0.05). ANA-positive APS and SLE-APS patients had similar clinical manifestations, and recurrences. Despite a limited follow-up (28 months (11-50)) none of the ANA-positive APS develop SLE. Antiplatelet and anticoagulant therapies were similar for the three groups. SLE-APS patients received more immunomodulatory therapies. ANA positivity in patients with APS enables to individualize a subset of patients with a more severe phenotype. Whereas the ANA positivity does not seem to be associated with the risk to develop SLE, prospective studies with a longer follow-up are necessary, in particular to evaluate the effect of additional therapies in this subset of APS.

ПРОГНОСТИЧЕСКИЕ МАРКЕРЫ У ПАЦИЕНТОВ С ТИМУСНЕЗАВИСИМОЙ И ТИМУСЗАВИСИМОЙ МИАСТЕНИЕЙ

Objective. To assess the presence of specific markers in patients with thymus-independent and thymus-dependent myasthenia gravis for choosing treatment tactics. Methods. The presence of specific markers was assessed in 138 patients with thymus-independent (M - myasthenia gravis without thymus changes) and thymus-dependent (MH - myasthenia gravis with thymus hyperplasia, MT - myasthenia gravis with thymoma). The method ELISA (the content of antibodies to subunits 1 and 7 nAChR in blood serum, to 7 nAChR subunit in thymocyte mitochondria, a detectablelevel of antinuclear antibody(ANA), immunofluorescence (ANA glow) and flow cytometry (expression of CD14+CD11c+and CD14 + HLA-DR +) has been used. Results. The relationship between the clinical phenotypes of myasthenia gravis and the variants of HLA diplotypes was revealed: in young patients with thymus-independent myasthenia gravis (M), a high heterogeneity of the genotypic markers HLA-DR (DR1, DR2, DR3, DR5, DR7) was detected. Patients with thymus-dependent myasthenia (MT) had only the HLA DR2 and HLA DR7 diplo- and haplotypes. The presence of HLA DR2 and HLA DR7 haplotypes in some young patients with progressive thymus-independent myasthenia gravis (M) led to the development of myasthenia gravis with thymoma (MT) in the elderly people. The pathogenic role also belongs to infection (СMV, EBV, HBV, HCV, HSV-1, HSV-2, HHV-6, mycoplasma) and food intolerance (IgE and IgG4) in the development and progression of myasthenia gravis. A four-fold prevalence of α7 subunit nicotinic acetylcholine receptors on the thymocyte mitochondria as an additional targets of autoimmune aggression in myasthenia gravis was determined. Specific antinuclear antibodies to centromere chromosome proteins were visualized in the elderly people with thymoma. Conclusion. The prognosis of the myasthenia gravis progression and the development of remission can be made using genomic (the presence of certain HLA-DR haplotypes) and molecular (ANA antibodies to centromere chromosome proteins, expression of CD20+, CD14+CD11c+, CD14+HLA-DR+) biomarkers, that can be used for the choice of treatment tactics. What this paper adds The change of complex biomarkers has been firstly studied for prognosis and choice of complex treatment tactics for young patients with progressive thymus-independent myasthenia gravis and for the elderly patients with thymus-dependent myasthenia gravis. In the presence of certain HLA-DR haplotypes, antinuclear antibodies to centromere chromosome proteins, an increasing expression of CD20+, CD14+CD11c+ and CD14+HLADR+ in some young patients with thymus-independent myasthenia gravis, analogically to biomarkers in thymus-dependent myasthenia gravis with thymoma, to perform a thymectomy is of high dangerous. potentialrisksof the procedure.

Autoantibody Profile of Egyptian Juvenile Systemic Lupus Erythematosus Patients and Its Association with Clinical Characteristics and Disease Activity.

ObjectiveThis study was conducted to estimate the frequency of anti-nuclear antibodies (ANAs), anti-dsDNA, and anti-extractable nuclear antigen (ENA) antibodies in juvenile systemic lupus erythematosus (JSLE) patients and their association with different clinical manifestations and disease activity.Patients and MethodsA cross-sectional study that includes 100 JSLE patients from Ain Shams University Hospital was conducted. All subjects underwent history taking, clinical examination, assessment of disease activity based on the SLE disease activity index (SLEDAI), laboratory investigations, and tests for autoantibodies, namely ANA, anti-dsDNA, and anti-ENA antibodies, including anti-Ro (SSA), anti-La (SSB), anti-Smith (Sm), and anti-U1-ribonucleoprotein (U1-RNP).ResultsThe most common clinical features were polyarthralgia (71%), haematological manifestations (65%), malar rash (54%), and nephritis (51%), respectively. All patients had positive ANA (100%), while anti-dsDNA frequency was 83%. The most common anti-ENA antibodies were anti-RNP (41%), anti-Sm (31%), anti-SSA (27%), and anti-SSB (20%), respectively. Anti-RNP had a clinical association with oral ulcer, Raynaud’ phenomena, haematological, neuropsychiatric and thromboembolic manifestations. Meanwhile, anti-Sm had a significant association with serositis, mucocutaneous, constitutional, and neuropsychiatric manifestations. Anti-SSA was associated with mucocutaneous, musculoskeletal, Raynaud’ phenomena, renal, haematological and cardiac manifestations, while anti-SSB was significantly associated with malar rash, serositis, thromboembolic, musculoskeletal, and neuropsychiatric manifestations. Concerning SLEADI score, anti-dsDNA antibody was significantly associated with moderate disease activity score (p=0.032) while anti-SSA significantly associated with high disease activity (p=0.045). Both anti-SSB and anti-Sm were significantly associated with both moderate and high disease activities, meanwhile anti-U1-RNP was associated with moderate disease activity (p=0.014).ConclusionAnti-dsDNA and anti-ENAs antibodies were frequently found in JSLE patients (83%, 63%), respectively. They were significantly associated with variable clinical manifestations and could be used as predictors for assessment of disease activity.

P148 ANA and Anti-dsDNA antibody enabling the prediction of inflammatory arthritis in inflammatory bowel disease

Abstract Background Inflammatory arthritis is frequent as an extraintestinal manifestation of IBD, as well as a paradoxical reaction to biological treatment. Anti-nuclear antibody (ANA) and Anti-dsDNA antibody have been associated with inflammatory arthritis. We aim to assess the correlation between the presence of ANA and Anti-dsDNA antibody and the diagnosis of inflammatory arthritis in patients with IBD under biological treatment. Methods We present a cohort study, including IBD patients under biological treatment, presenting at least a treatment session in the first 2 months of 2020. Data was gathered from medical records, laboratorial analysis, namely ANA and Anti-dsDNA, were collected in the treatment session, and every patient posteriorly answered telephonically validated questionnaires to assess the presence of inflammatory arthritis, the outcome variable. A univariate analysis followed by a multivariate logistic regression, including statistically significant variables, tested the correlation towards inflammatory arthritis. A ROC curve tested the performance of the final model. Results We included 122 patients, 64 (52.5%) were women, and the mean age was 39 years old. Eighty-six (70.5%) patients presented Crohn’s Disease and 36 (29.5%) Ulcerative Colitis. A hundred (82%) patients were under Infliximab, 21 under Vedolizumab (17.2%) and only 1(0.8%) under Adalimumab. Thirty-three patients (27%) met questionnaire criteria for inflammatory arthritis, either peripheric or axial. The variables age, ANA and ANA’s title, age at IBD diagnosis and number of symptomatic articulations involved were associated with the presence of inflammatory arthritis. The multivariate model including ANA (OR 4.149 [1.03–16.711] p=0.045); number of articulations involved (OR 2.683 [1.783–4.038] p&amp;lt;0.001) and higher age at IBD diagnosis, accurately identified patients with diagnosis of inflammatory arthritis (ROC AUC 0.957 [0.926–0.987] p&amp;lt;0.001). A sub-analysis correlating ANA and the presence of inflammatory arthritis after biological initiation showed a statistical tendency (OR 2.231 [0.908–5.478] p&amp;lt;0.08). Conclusion The presence of ANA antibodies and a higher number of symptomatic articulations involved independently increased the rate of inflammatory arthritis diagnosis in up to 4 times, in a cohort of patients with IBD under biological treatment. The inclusion in a multivariate model displayed an excellent accuracy and performance towards the diagnosis of inflammatory arthritis. ANA antibodies together with validated questionaries may aid in the identification of IBD patients suffering from inflammatory arthritis.

Sensorineural Hearing Loss and Systemic Autoimmune Disease: The Experience of a Systemic Immune-Mediated Diseases Unit.

BackgroundAutoimmune inner ear disease (AIED) represents less than 1% of all cases of sensorineural hearing loss (SNHL) but its frequency may be underestimated due to lack of specific clinical and laboratory criteria. AIED can be associated with a systemic autoimmune disease (SAID) in 15%-30% of the cases. The objective of the present study was to characterize the clinical and prognostic factors of a cohort of patients with AIED.Materials and methodsThe authors conducted a retrospective descriptive analysis of a cohort of patients with AIED referred from the otorhinolaryngology department to a systemic immune-mediated diseases unit between March 2013 and November 2020. A consecutive sample of 39 patients with suspected AIED was referred. SNHL was defined as a fall of the hearing threshold of at least 30 decibels in three consecutive frequencies. Eight patients were excluded for not meeting the audiometric criteria or having confounding factors. The remaining 31 patients were included with a total of 50 affected ears. To classify the intensity of hearing loss, an arithmetic mean of pure tone was calculated. Normal hearing or mild hearing loss at the last pure tone audiometry of the follow-up were an indicator of good prognosis and were considered the outcome of interest.ResultsThirty-two percent of the patients had an associated SAID. There were no differences regarding demographic and clinical characteristics when comparing patients with AIED alone and patients with AIED and a SAID, except for the positivity of antinuclear antibodies (ANA). ANA positivity was superior in patients with the association of AIED and a SAID when compared with patients with AIED alone (90% vs 50%; p=0.037). The SAID was diagnosed after the AIED in 70% of the patients, in which diagnosis of the SAID occurred a median of 4,2 (IQR 0.8-5.1) years after the diagnosis of the AIED. Normal audiometric evaluation or a mild hearing loss was achieved in 31% of the ears at the last audiometric evaluation. A normal audiometry or a mild hearing loss at the time of diagnosis was independently associated with a better outcome (31%, 14%, CI 1.71-273.69; p=0.018). Bilateral hearing loss was independently associated with a worse outcome (54%, 79%, CI 0.01-0.84; p=0.035). The use of systemic corticosteroids (p=0.941), transtympanic corticosteroids (p=0.700) and non-steroid immunomodulator drugs (p=0.986) did not affect prognosis. The presence of a SIAD did not affect the prognosis (p=0.986).ConclusionsIn this cohort, SAID was present in one-third of the patients with AIED. A good prognosis was achieved in one-third of the patients. A normal audiometry or mild disease at presentation was associated with a good outcome, whilst bilateral involvement was associated with a bad one. Association of a SAID did not seem to influence the hearing-related prognosis. Positivity of ANA antibodies may justify performing a complementary investigation to determine the presence of a SAID.

Glomerular Diseases Associated with Malignancies: Histopathological Pattern and Association with Circulating Autoantibodies.

Aim: Glomerular diseases (GD) associated with malignancies (AM, GDAM) have unique features, which are important to recognize, in the light of the progress made in cancer therapy. We aimed to describe the clinical and histopathological characteristics of patients with GDAM in relation to the presence of circulating autoantibodies, pointing to potential immune pathogenic pathways connecting cancer to GD. Materials and Methods: The included patients were studied retrospectively on the basis of a kidney biopsy proving GD and a related biopsy to establish the diagnosis of AM. We recorded patients’ demographics, serological and laboratory parameters, histopathological findings, and the type of malignancy, GD, and therapy. Results: In total, 41 patients with GDAM, with a mean age of 63.1 (±10.7) years, were studied. In 28 (68.3%) cases, GD was associated with a solid tumor, and in 13 (31.7%) patients with a lymphoid malignancy. The most frequent histopathological pattern was membranous nephropathy (43.9%). Overall, at the time of GD diagnosis, 17% of the patients were positive for antinuclear antibodies (ANA), and 12.2% for antineutrophil cytoplasmic autoantibodies (ANCA), all against myeloperoxidase (MPO). In addition, 93.3% of the patients who had membranous nephropathy were negative for transmembrane glycoprotein M-type phospholipase A2 receptor (PLA2R) antibody. Sixteen patients (39.0%) presented with acute nephritic syndrome, of whom five (31.25%) developed rapidly progressive glomerulonephritis. In a mean follow-up time of 36.1 (±28.3) months, nine (21.95%) patients ended up with end-stage kidney disease, and eight (19.5%) died. Conclusion: We found that 3.2% of patients who underwent a native kidney biopsy in our institution during the past decade, for any reason, were identified as having some type of GD associated with a malignancy. Serology indicated a significant presence of ANA or MPO-ANCA antibodies in patients with nephritic syndrome and the absence of PLA2R antibodies in patients with membranous nephropathy.

Assessment of a high-avidity IgG ANAs for the diagnosis and activity prediction of systemic lupus erythematosus.

Our aim was to investigate the prevalence value of a high-avidity antinuclear antibody (ANA) of the IgG isotype (HA IgG ANA) compared with that of ANAs of other isotypes in patients with systemic lupus erythematosus (SLE) and to assess the associations of HA IgG ANA with the activity of SLE and lupus nephritis. We retrospectively analyzed clinical and laboratory data from subjects. Blood samples were acquired from 101 SLE patients, 67 patients with other autoimmune diseases, and 65 healthy donors. The levels of HA IgG ANA and other isotype ANAs were measured by indirect immunofluorescence (IIF). The prevalence and diagnosis value of HA IgG ANA and other antibodies in SLE patient were tested. The advantage of HA IgG ANA compared with HA anti-dsDNA antibodies IgG (HA dsDNA IgG) was verified by ELISA. We monitored the relative avidity indexes (RAIs) of HA IgG ANA and HA dsDNA IgG at 3 time points after the start of treatment in the same individuals with SLE. The prevalence of HA IgG ANA was significantly higher in active cases than in inactive cases of SLE and LN, which is consistent with data for IgG ANAs, anti-dsDNA IgG antibodies, low C3 levels, low C4 levels, and anti-C1q antibodies. HA IgG ANA showed moderate sensitivity and specificity (80% and 81.3%) for discriminating active and inactive SLE cases. However, HA IgG ANA showed no significant differences among the different clinical manifestations of SLE. Compared with that of HA dsDNA IgG, the RAI of HA IgG ANA was positively related to SLEDAI scores after treatment at 0, 1, and 3months (r = 0.6813, p = 0.0026; r = 0.5972, p = 0.0114; r = 0.4817, p = 0.0474). First, we demonstrated that HA IgG ANA was a reliable diagnostic tool in SLE patients. Furthermore, HA IgG ANA was supposed to be more appropriate for identifying the activity of SLE compared with HA dsDNA IgG. In summary, HA IgG ANA may be a new biomarker for diagnosing SLE and identifying SLE activity. Key Points • We first introduced the concept of a "high-avidity IgG ANA (HA IgG ANA)" that could distinguish between the early stage of SLE and SLE that had been active for some time. • The relative avidity indexes (RAIs) of HA IgG ANA and HA dsDNA IgG were presented and applied here to evaluate the avidities of antibodies involved in SLE. • In our study, we confirmed the value of HA IgG ANA in diagnosing SLE. In addition, HA IgG ANA was more appropriate for identifying the activity of SLE than was HA dsDNA IgG. • In conclusion, HA IgG ANA could be a potential biomarker for the assessment of the prognosis of SLE activity.

Efekat hiperbarične oksigenoterapije na kvalitet života i stanje mikrocirkulacije kod bolesnika sa sistemskom sklerozom

Introduction: Systemic sclerosis (SSC) is a rare, chronic, progressive, severe illness with unknown etiology and characteristics of impaired microcirculation. The effect of hyperbaric oxygen therapy (HBOT) is reflected in the efficiency of pure oxygen under pressure greater than atmospheric and it is main indication for the application in the state of disturbed microcirculation. Aim: The aim was to examine the effect of HBOT on the quality of life and the state of microcirculation in patients with SSc. Material and methods: The research represents retrospective study which involved 18 female patients with SSc. All patients completed the HAQ, SySQ and TIFS questionnaires and all basic laboratory analyzes, as well as total anti-nuclear antibodies (ANA), anti-centromer antibodies (ACA), and anti-topoisomerase-1 antibodies (Anti-Scl-70). Rodnan skin score, capillaroscopy, and diffusion spirometry were made and values of forced vital capacity (FVC) and lung diffusion capacity for carbon monoxide (DLco) were taken. Results: FVC values were 96.61 ± 13.44 (78 - 122) before departure, but after treatment they were 115.94 ± 16.69 (82 - 135). DLco values were 73.61 ± 6.63 before departure, after departure results were 87.33 ± 9.30. ANA antibodies were positive in 38.9%, ACA were positive in 22.2%, and Anti-Scl-70 were positive in 16.7%. The mean value of ESR was 20.5 (4 - 42) before going to the hyperbaric chamber, and after departure it was 12 (3 - 27). Conclusion: Our research has shown that HBOT has a significant effect on patients with SSc, but further research is needed to determine the exact effect of HBOT on this disease.

Exploring Systemic Autoimmunity in Thyroid Disease Subjects.

Introduction Individuals with one autoimmune disease are at risk of developing a second autoimmune disease, but the pathogenesis or the sequential occurrence of multiple autoimmune diseases has not been established yet. In this study, we explored the association and sequential occurrence of antibodies in thyroid disease and systemic autoimmune disease subjects. We evaluated thyroid hormones, thyroid-stimulating hormone (TSH), free thyroxine (FT4), thyroid autoantibodies, anti-thyroperoxidase (anti-TPO), and anti-thyroglobulin (Tg) to comprehend the association with systemic autoimmune autoantibodies, anti-nuclear antibodies (ANA), and autoantibodies to extractable nuclear antigens (ENA) in subjects with thyroid-related symptoms. Methods A total of 14825 subjects with thyroid-related symptoms were tested at Vibrant America Clinical Laboratory for thyroid markers (TSH, FT4, anti-TPO, and anti-Tg) and an autoimmune panel (ANA panel and ENA-11 profile) from March 2016 to May 2018. Thyroid-positive (based on TSH and FT4 levels), anti-TPO-positive, and anti-Tg-positive subjects were assessed for the prevalence of ANA and anti-ENA antibodies. A 2-year follow-up study was conducted to assess the sequential order of appearance of autoimmune markers in thyroid and systemic autoimmune diseases. Results In the retrospective analysis, 343/1671 (20.5%), 2037/11235 (18.1%), and 1658/9349 (17.7%) of thyroid+, anti-TPO+, and anti-Tg+ subjects were found to be seropositive for ANA. Anti-ENA was detected in a higher prevalence than ANA with 475/1671 (28.4%), 3063/11235 (27.3%), and 2511/9349 (26.9%) in the same groups of subjects, respectively. Our results are found to be much higher than the reported prevalence of anti-ENA in general population. During the 2-year follow-up study, anti-TPO appeared significantly earlier than ANA and anti-ENA in an average of 253 (±139) and 227 (±127) days, respectively. Conclusions A high prevalence of anti-ENA and ANA was found to be coexisting with autoimmune thyroid disease subjects, with anti-TPO occurring prior to the onset of ANA and anti-ENA. Therefore, frequent follow-ups and evaluation of ANA and anti-ENA in subjects with anti-TPO positivity would be beneficial in early detection of other systemic autoimmune diseases.

Pericardial Effusion Due to Infliximab Therapy for Ulcerative Colitis

Ulcerative colitis (UC) is characterized by ulcers and inflammation of the colon, with anti tumor necrosis factor alpha (anti-TNF alpha) therapy as a mainstay for treatment. Side effects include anti-TNF alpha induced lupus (ATIL), which consists mostly of arthralgias and cutaneous manifestations with rare cases of pleural or pericardial effusions. Serology shows positive anti nuclear antibodies (ANA) (79%), positive anti double stranded DNA (ds-DNA) antibodies (72%) and rarely anti histone antibodies (17-57%). We present a case of infliximab induced pericardial effusion (PE). A 51 year old female with UC on mesalamine, presented to clinic with watery diarrhea and abdominal pain. She was prescribed budesonide and prednisone with no improvement, so infliximab therapy was initiated. 2 weeks after receiving her 1st dose of infliximab 500 mg, she developed shortness of breath, mid sternal chest pain and fatigue. A transthoracic echocardiogram showed a small to moderate PE present more anteriorly and less prominent on the apical, inferior and subcostal views. Criteria for cardiac tamponade was not met. Due to the anatomical location of the effusion, a pericardiocentesis was not done. Workup for the etiology of the PE including HIV, monospot, T-spot, ANA, and anti ds-DNA antibody was negative. Anti histone antibodies were 1.9 (positive). Due to the timeline of her symptoms corresponding with infliximab, a diagnosis of ATIL was made. Infliximab was stopped and in a few days her symptoms resolved. She was later switched to vedolizumab for UC with no adverse effects. No definitive criteria is present to diagnose ATIL. However, early diagnosis of ATIL requires an association between symptoms and the drug, at least one serologic American College of Rheumatology (ACR) criteria (ANA, anti ds-DNA antibodies, anti histone antibodies) and one non serologic ACR criteria (arthritis, serositis, rash). This case is a rare presentation of infliximab induced lupus, presenting as PE with negative ANA and anti ds-DNA antibodies, but positive anti histone antibodies. Ideal treatment is discontinuation of the drug. Steroids may be required in some cases. Alternate therapy for UC like vedolizumab has been shown to be effective and safe. After vedolizumab therapy, our patient had complete resolution of symptoms with no side effects. Further research is warranted to come up with a definitive criteria for diagnosis of ATIL given its life threatening and variable manifestations.2087_A Figure 1. Parasternal long axis view of the pericardial effusion.2087_B Figure 2. Subcostal view of the pericardial effusion.2087_C Figure 3. Timeline of the symptoms.

Induced carotid atherosclerosis in lupus mice

ABSTRACTFas knockout (Fas−/-) mice are a model for systemic lupus erythematosus (SLE) -like autoimmune syndromes. We aimed to induce atherosclerosis (AS) in Fas−/- mice. Sixteen male Fas−/- mice were included in the study, sex-matched C57B6/L (B6) and apolipoprotein E-knockout (ApoE−/-) mice were negative and positive AS controls, respectively. A silica collar was placed around the right carotid artery of each mouse to induce AS development. All mice were fed a 24-week high-fat diet, and investigated for AS lesions. We also compared the levels of blood lipid and glucose, serum tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), anti-nuclear antibody (ANA) and anti-double-stranded deoxyribonucleic acid (anti-dsDNA) antibody in Fas−/- mice with those in B6 or ApoE−/- mice. All ApoE−/- and 6 Fas−/- but no B6 mice showed atherogenesis in right carotid artery. The carotid plaque contains more collagen and less lipid in Fas−/- than ApoE−/- mice. The levels of blood glucose, serum TNF-α, IL-6, ANA, and anti-dsDNA antibody were significantly higher in Fas−/- mice than those in B6 mice, the levels of serum TNF-α and blood glucose were significantly higher and the level of blood lipid was significantly lower in Fas−/- mice than those in ApoE−/- mice. Therefore, carotid AS can develop in Fas−/- mice. Fas−/- mice display higher levels of serum IL-6, TNF-α, ANA, and anti-dsDNA than B6 mice, higher levels of serum TNF-α and blood glucose and lower level of blood lipid than ApoE−/- mice, and less lipid and more collagen in AS plaque than ApoE−/- mice.