Antinuclear Antibody Titer Research Articles

Up-Regulated Interleukin-10 Induced by E2F Transcription Factor 2-MicroRNA-17-5p Circuitry in Extrafollicular Effector B Cells Contributes to Autoantibody Production in Systemic Lupus Erythematosus.

Elevated interleukin-10 (IL-10) levels in patients with systemic lupus erythematosus (SLE) have B cell-promoting effects, contributing to autoantibody production and tissue damage. We aimed to characterize up-regulated IL-10+ B cell subsets and dysregulated IL10 expression in SLE B cells for new therapeutic options. Proportions of Th10 and IL-10+ B cell subsets in peripheral blood mononuclear cells (PBMCs) were assessed using flow cytometry. The IL10 3'-untranslated region (3'-UTR) dual-luciferase vector was constructed and cotransfected with small interfering RNA (siRNA), microRNA (miRNA) mimics, or miRNA inhibitors into Raji cells. Transcript levels were quantified using TaqMan assays. Culture conditions that induced IL-10+ Breg cells in healthy controls resulted in expansion of IL-10+ double-negative 2 (DN2; IgD-CD27-CD21-CD11c+) B cells in SLE PBMCs. Proportions of IL-10+ DN2, but not those of IL-10- DN2, correlated with disease activity and levels of antibodies to double-stranded DNA (dsDNA) (r = 0.60, P = 0.03 for cohort 1; r = 0.38, P = 0.03 for cohort 2), and were associated with high levels or seropositivity of anti-Sm (P = 0.03 for cohort 1; P = 0.01 for cohort 2) and IgG anticardiolipin (P < 0.01 for cohort 1; P = 0.02 for cohort 2) in SLE patients from 2 cohorts, of mainly African American subjects (cohort 1) and of Asian subjects (cohort 2). Proportions of Th10 (CD45RA-CXCR5-CXCR3+PD-1high CD4+) cells correlated with IL-10+ DN2 frequencies (r = 0.60, P < 0.01 for cohort 2), antinuclear antibody titers (r = 0.52, P = 0.01 for cohort 2), and proteinuria levels (r = 0.72, P < 0.01 for cohort 2) in SLE patients. Screening of predicted IL10 3'-UTR-targeting miRNAs in SLE B cells identified miRNA-17-5p (miR-17-5p) and miR-20a-5p, with their levels inversely correlated with IL10 (r = -0.47, P < 0.01 for miR-17-5p; r = -0.37, P = 0.03 for miR-20-5p) and transcription factor E2F2 (r = -0.48, P = 0.04 for miR-17-5p; r = -0.45, P = 0.05 for miR-20-5p). In Raji cells, knockdown of E2F2 expression resulted in increased levels of miR-17-5p and miR-20a-5p and decreased IL10 messenger RNA (mRNA) and protein levels, and overexpression and inhibition of miR-17-5p down-regulated and up-regulated, respectively, IL10 mRNA levels, suggesting regulation of IL10 expression by an E2F2-miR-17-5p loop. IL-10 promotes extrafollicular autoimmune responses in patients with active SLE, which might be dampened by targeting the E2F2-miR-17-5p circuitry.

High titers of antinuclear antibody and the presence of multiple autoantibodies are highly suggestive of systemic lupus erythematosus

The aim of this study is to evaluate the relationship between antinuclear antibody (ANA) titer and specificity, as well as the relationship between the number of positive-autoantibodies (AAbs) in antinuclear antibodies (ANAs) and specificity for systemic lupus erythematosus (SLE), so as to explore their significance in the diagnosis of SLE. A total of 1297 patients with ANA results was enrolled in this study, including 148 patients with SLE patients. The sensitivity, specificity, sensitive likelihood ratio and specific likelihood ratio of indicators in SLE were determined by receiver–operator characteristic (ROC) curve after measurement of ANA and ANAs by indirect immunofluorescence (IIF) and immunoblotting, respectively. ROC analysis showed that the specificity of ANA titer ≥ 1 +, ≥ 2 + and ≥ 3 + for SLE was estimated to be 81.29%, 90.69% and 96.52% respectively, with a increased titer-specific likelihood ratio (5.16, 9.29 and 19.60, respectively). The specificity of the number of positive-AAbs ≥ 1, ≥ 2 and ≥ 3 in ANAs for SLE was estimated to be 80.42%, 94.95% and 99.3% respectively, with a increased number-specific likelihood ratio (4.8, 15.26 and 72.48, respectively). The estimated sensitivity of the number of positive-AAbs ≥ 3, AnuA and anti-rRNP was higher than that of anti-Sm (p < 0.01) (50.68%, 41.89% and 31.76% vs. 16.89%, respectively), while there was no significant difference in their specificity (99.3%, 99.74% and 99.56% vs. 99.74%, respectively) (p > 0.05). High titers of ANA and the presence of multiple AAbs in ANAs are highly specific for SLE and highly suggestive of SLE. The likelihood of SLE can be assessed by ANA titer and the number of positive-AAbs in ANAs.

New Clinical Phenotype of the Post-Covid Syndrome: Fibromyalgia and Joint Hypermobility Condition.

Fibromyalgia can be defined as a chronic pain condition, affecting the musculoskeletal system, etiology and pathophysiology of which is sufficiently understudied. Despite the fact that many authors consider this entity to be a manifestation of central sensitization, and not an autoimmune disease, the high prevalence of fibromyalgia in patients with post-COVID-19 conditions requires taking a fresh look at the causes of the disease development. During the patient examination, the authors identified a combination of symptoms that occurs so often, that they can be carefully described as a clinical pattern. These manifestations include young age, female gender, joint hypermobility, the onset of pain after COVID-19, physical traumatization of one particular tendon and the development of the fibromyalgia pain syndrome during the next several weeks. As well as an increase in the titer of antinuclear antibodies and some other systemic inflammation factors. It can be assumed with great caution that local damage to the connective tissue in patients with joint hypermobility, having COVID-19 as a trigger factor can lead to the development of fibromyalgia syndrome. This article presents three clinical cases that illustrated this hypothesis.

Correlation of ANA Characteristics with pANCA IFA Interference.

Antineutrophil cytoplasmic antibody (ANCA) testing by the indirect immunofluorescence assay (IFA) is important for the diagnosis of autoimmune vasculitis. A common analytical interference for ANCA-IFA is the presence of an antinuclear antibody (ANA), which can cause an apparent perinuclear ANCA (pANCA) result on ethanol-fixed neutrophils. Here, the association of ANA patterns, titers, and concentrations with pANCA interference is investigated. Samples positive for ANA by IFA with homogeneous, speckled, dense fine speckled (DFS), and centromere patterns were tested for ANA by enzyme immunoassay (EIA)] and for ANCA by IFA on ethanol-fixed neutrophils. Titers and concentrations were determined for the ANA-IFA and EIA, respectively, and correlated with the frequency of pANCA interpretations. For ANA-EIA positive samples (≥1.1U), 20.0% led to a pANCA interpretation compared to 5.1% for negative samples (≤1.0U). For samples positive by ANA-IFA, 12.9% resulted in a pANCA interpretation. Interference on pANCA correlated with ANA-IFA titer, with ANA titers ≥1:1280 identified as pANCA positive in 20.9% of samples compared to 9.7% for titers <1:1280. There was also a correlation with ANA pattern, as homogeneous samples were most likely to be called positive for pANCA (31.7%), followed by speckled (8.8%), DFS (6.8%), and centromere (3.6%). Positivity for ANA by EIA is associated with increased prevalence of pANCA interpretation. Samples positive for ANA by IFA also demonstrated this association, particularly with higher-titer, homogeneous patterns. Laboratories can use this information to determine an optimal workflow for when investigating potential pANCA interferences.

Salivary anti-nuclear antibody (ANA) mirrors serum ANA in systemic lupus erythematosus

ObjectivesTo assay salivary anti-nuclear antibody (ANA) and its isotypes in patients with systemic lupus erythematosus (SLE) and to investigate relevant clinical associations.MethodsSaliva samples were collected from SLE patients and assayed for salivary ANA using immunofluorescence (IF). Isotypes of salivary ANA, including IgG-ANA, IgA-ANA, and IgM-ANA, were quantified using enzyme-linked immunosorbent assay. The correlations between clinical parameters and levels of salivary ANA and isotypes were evaluated.ResultsSalivary ANA IF intensities were significantly higher in SLE patients than in healthy controls, irrespective of SLE patient disease activity, and strongly correlated with serum ANA titers. Salivary ANA was detected in 67.14% of SLE patients and 10.00% of healthy controls (p < 0.001). Among ANA-positive samples, 80.85% exhibited a nuclear ANA pattern, and 42.55% exhibited a cytoplasmic ANA pattern. Salivary IgG-ANA, IgA-ANA, and IgM-ANA levels, as assayed by ELISA, were significantly increased in both active and less active SLE patients compared with healthy controls, and levels of each isotype were significantly correlated with serum ANA titer. Salivary IgM-ANA levels correlated with the physician global assessment (PGA), SLE disease activity index (SLEDAI), and negatively with serum C3 and C4. Salivary IgG-ANA also correlated with erythrocyte sedimentation rate (ESR), SLEDAI, and negatively with serum C3.ConclusionSalivary ANA levels correlate with serum ANA titer, and salivary IgM-ANA and IgG-ANA correlate variably with PGA, SLEDAI, ESR and complement levels. These findings underscore the potential of using salivary ANA and ANA isotypes as surrogates for serum ANA, particularly for future point-of-care applications since saliva is easier to obtain than blood.

Diagnostic Value of Anti-Nuclear Antibodies: Results From Korean University-Affiliated Hospitals.

BackgroundUnnecessary and inappropriate laboratory testing accounts for a significant portion of waste in health care utilization. The aim of this study was to examine the diagnostic value of the anti-nuclear antibody (ANA) test by examining the rate of ANA associated rheumatic disease (AARD) diagnosis among ANA tested and ANA positive subjects and positive predictive value (PPV) of ANA test leading to AARD diagnosis in different ANA titers and different subsets of patients in 5 hospitals affiliated with a university.MethodsWe retrospectively extracted data from all subjects who were tested for ANA from year 2010 to 2019. Those who were first evaluated at or referred to rheumatology were further evaluated with extraction of data including ANA titer and ultimate diagnosis. PPVs for ANA test were evaluated after stratification according to clinically relevant key parameters, such as patient age (younger < 65 years vs. older), sex, and requesting department.ResultsFrom 2010 to 2019, A total of 94,153 patients were tested for ANA, of which 13,600 (14.4% of the total) were positive. AARD was diagnosed in only 0.69% among all ANA tested patients and 4.74% among ANA positive patients. The AARD diagnosis rate of ANA positive patients varied widely from 0.1% to 8.7% by requesting department. Using cutoff values above 1:320 yielded PPVs of 15.6 and 7.8% for all AARs and systemic lupus erythematosus. The PPV was significantly higher in young age (< 65 years) and in women, and when it was requested from internal medicine vs other departments.ConclusionAARD was diagnosed in less than 1% of all ANA tested patients in university-affiliated hospitals. This result shows that careful consideration before ordering the screening ANA is needed to improve the utility of the test for providers and patients and to reduce health costs spurred by unnecessary testing and its consequences.

A case of Erythroderma following Terbinafine therapy

Background: The onset of cutaneous lupus erythematosus may be associated with the administration of a variety of drugs. Terbinafine, an oral antifungal agent, which rarely causes cutaneous eruptions, has been implicated as the cause or exacerbation of cutaneous lupus erythematosus in several patients. Case: A 52-year-old female patient had received oral terbinafine for onychomycosis. The patient had a family history of lupus, but no personal history. Six weeks after initiating treatment with terbinafine the patient developed cutaneous lupus which was diagnosed clinically and by histology. She developed an erythrodermic rash. Immunological studies showed elevated titres of anti-nuclear antibodies. Following discontinuation of terbinafine therapy and under the treatment of systemic and topical steroids, a slow resolution of the eruption was noted over several weeks. Conclusions: This report, along with previous cases described, suggests the association between terbinafine therapy and the onset or exacerbation of SLE often occurring in a patient with history of systemic lupus erythematosus or SLE. Key words: SLE, erythroderma, drug reactions

Comorbid laboratory abnormalities in female pattern hair loss patients

Background: Female pattern hair loss (FPHL) is the main cause of alopecia in women and has a debilitating impact on the quality of life. However, certain comorbid conditions causing hair loss are often masked by FPHL and may remain undetected. Hence, it is imperative to identify them to administer appropriate treatment. The necessity of laboratory tests to evaluate these comorbidities in patients with FPHL has not been established. Objectives: This study aimed to identify the frequency of comorbid abnormalities detected by laboratory tests in patients with FPHL. Methods: Routine laboratory test results of patients with FPHL, who visit our hair clinic for the first time, were retrospectively collected and analyzed. These tests assessed the serum testosterone, thyroid-stimulating hormone, free thyroxin, zinc and ferritin levels, hemoglobin, as well as antinuclear antibody (ANA), and rapid plasma reagin test results. The correlation between age and hair loss severity and the frequency of comorbidities was evaluated using subgroup analysis. Results: Among the 356 patients with FPHL, coexisting zinc deficiency, iron depletion, and thyroid abnormalities were common and present in 41.7%, 39.7%, and 11.3% of them, respectively. The rate of concomitantly increased ANA titers was relatively low (4.4%), while that of syphilis and high serum testosterone levels was extremely low (0.3% and 0%, respectively). Younger patients (<50 years) with FPHL had a higher rate of coexisting iron deficiency than patients in the older age group. Conclusion: Testing for concomitant iron depletion, zinc deficiency, and thyroid disease is recommended in female patients with FPHL.

A rare case of Interstitial lung disease complicated by overlapping syndrome with obstructive ventilatory dysfunction as the first symptom

Interstitial lung disease is often a serious complication of connective tissue disease（CTD）, representing the first cause of death in CTD. However, there are few reports of SSc-RA overlap-associated interstitial pneumonia. Respiratory dysfunction as the first clinical manifestation is even rarely reported. We herein described a case of a male patient who developed significant respiratory dysfunction as the principal clinical sign for the past 6 months, plus newly developed skin thickening in bilateral upper limbs and pain and swelling of multiple joints for the past 6 weeks. Extensive immunological screening showed high titer of antinuclear antibodies(ANA), rheumatoid factor(RF), anti-cyclic peptide containing citrulline (anti-CCP)，and positive anti-Scl-70 antibody. Chest high resolution computed tomography(HRCT) was performed and hence ILD was confirmed. Pulmonary function test (PFT) revealed obstructive ventilatory dysfunction rather than restrictive ventilatory dysfunction. So bronchodilation test was performed and asthma was considered. Finally, after a multidisciplinary team (MDT) discussion, the diagnosis of asthma and ILD associated with SSc-RA overlap was established. It is important to note that CTD associated pulmonary interstitial fibrosis must be considered as the differential diagnosis of any newly diagnosed interstitial pulmonary disease. In addition, if patient with dyspnea is highly suspicious of pulmonary interstitial fibrosis, bronchodilation test is still needed to exclude asthma in order to avoid misdiagnosis.

Autoantibodies to dense-fine-speckled 70 (DFS70) do not necessarily rule out connective tissue diseases

ObjectivesIn some patients with antinuclear antibodies (ANA), a pattern called anti-dense-fine-speckled-70 antibody (anti-DFS70) can be detected. Presence of anti-DFS70 is less frequently observed in patients with connective tissue diseases (CTD) and is therefore used as an exclusion criterion by some rheumatologists. To date, however, it is unclear as to what extent the presence of an anti-DFS70 can reliably rule out CTDs. MethodsData of 460 patients who were tested for the presence of anti-DFS70 at University Hospital Bonn, Germany, were analyzed. Patients were examined with regard to clinical symptoms and signs, type of disease, type of CTD, fulfillment of the classification criteria, presence of anti-DFS70, other systemic autoantibodies and ANA titers by indirect immunofluorescence (IIF) assays and line immunoassays. Differences in DFS70 antibody status between patients with CTD were examined. In addition, specificity, sensitivity, and positive predictive values for different ANA titers were calculated. ResultsIn 182 of the 460 patients (of whom 79.8% were female), CTD was diagnosed. 354 patients (77.0%) tested negative, 81 (17.6%) positive and 25 (5.4%) borderline for anti-DFS70. Twenty-one patients (25.9%) with a positive result had CTD. No significant differences were observed between anti-DFS70 positive and anti-DFS70 negative patients with CTD concerning age, gender, symptoms, clinical signs, and other disease-specific antibodies. However, of these 21 patients, only one patient showed the monospecific appearance of anti-DFS70. Anti-DFS70 had a sensitivity and a specificity of 26.9% and 86.8%, respectively, with a positive predictive value of 68.2% at an ANA titer of ≥1:160 with respect to the absence of CTD. ConclusionsAutoantibodies to DFS70 seem to be prevalent in CTD patients and are thus not a good exclusion criterion. The monospecific occurrence of anti-DFS70 can, however, be helpful in ambiguous situations.

Study of the D-dimer, C-reactive protein, and autoantibodies markers among HBV infected patients in Babylon province, Iraq.

BackgroundHepatitis B can be defined as one of the dangerous diseases caused by the hepatitis B virus (HBV), which infects the liver and causes liver failure, cirrhosis, and death.AimsThis study aimed to evaluate the D-dimer, C-reactive protein (CRP), and autoantibodies markers among HBV-infected patients in Babylon province, Iraq, compared to a healthy control group.MethodsIn this cross-sectional study, all patients referred to GIT and liver centers in Merjan Medical City, Babylon, Iraq from January 2016 to January 2018 were screened for HBV infection by quantitative real-time polymerase chain reaction (qPCR). Antinuclear antibody (ANA), dsDNA, D-dimer, and CRP markers were examined using fluorescence technique in randomly selected patients and some healthy individuals as control group. Statistical analysis was performed using SPSS program.ResultsIn this study, 424 HBV patients from different areas of Babylon province, Iraq were enrolled. A total of 40 patients and 15 healthy participants were selected for evaluation of D-dimer, CRP, ANA, and dsDNA levels. The results of the distribution of HBV-infected patient by gender per area revealed that males accounted for a higher percentage than females in all parts of Babylon provinces. Also, a highly significant increase in serum levels was observed in the patients compared to the control subjects for all the studied parameters D-dimer, ANA, dsDNA, and CRP. Overall, 5.5% of HBV patients (3/40) had a positive ANA titer. None of the HBV patients had a positive dsDNA titer.ConclusionThis study showed that, HBV-infected patients had elevated levels of D-dimer and CRP compared to the control group. Also, the seropositivity titers of ANA and anti-dsDNA autoantibodies were low in Iraqi HBV patients.

Acute Kidney Injury and Proteinuria in a Man With Hemoptysis

Acute Kidney Injury and Proteinuria in a Man With Hemoptysis

P048 Juvenile systemic lupus erythematosus, what specificities?

Abstract Background Juvenile systemic lupus erythematosus (J-SLE) is a chronic autoimmune disease characterized by multi-visceral involvement with an unpredictable prognosis. The diagnosis is usually made in young women between the ages of 20 and 40, however, it can set in at any age and will be classified as juvenile (LESj) when it begins before the age of 16.We report the epidemiological, clinical, therapeutic and evolutionary characteristics of a retrospective series carried out at the level of the pediatric center—CHU de Sétif comprising 13 girls and one boy. Methods The mean age of onset is 12 years and 3 months, the mean time to diagnosis is 7 months. The clinical picture is made of e reached articulaire skin and e fever in 86% respectively 57% and 57% of cases, followed by kidney disease in 57% of cases. Cardiac involvement pulmon area ophtalmologiqu e is referred to in low percentages. The blood reached logic of étectée on blood counts in 85% of patient e s i and the syndrome nflammatoire was almost constant. A positive titer of antinuclear antibodies and anti- AD Nn is objectified, as well as a reduction in the level of complement. The anti-GP 2 and anti- cardio lopine antibodies are positive in 57% of cases. Has the present hue kidney in 42% of cases. A single case of overlap syndrome with dermatomyositis has been reported. As for the neurological form, only one adolescent presented it. With a single case of familial lupus and a single case of Rhupus. Results The diagnosis is based on the American College of Rheumatology (ACR) 1982 classification revised in 1997 and the new SLICC “Systemic Lupus International Collaborating Clinics” criteria. The clinical characteristics of our series are consistent with the overall data in the literature with a predominance of cutaneous and joint involvement. with however some specific characteristics which are individualized by a more advanced age of onset, of 13 years on average in our study vs 10 years and 12 years, the rarity of the familial forms (1 case), a lower percentage of renal damage (42% vs 63% and 80%). The therapeutic management was based on corticosteroids and Hydroxychloroquine in most cases, the use of immunosuppressants was reserved for x severe. Conclusion Lupus is an autoimmune disease with protean clinical manifestations, the prognosis of which is dominated by renal, neurological and thrombotic damage. Corticosteroid treatments and immunosuppressants markedly improved the vital prognosis.

Predicting Chronic Immune Thrombocytopenia in Pediatric Patients at Disease Presentation: Leveraging Clinical and Laboratory Characteristics Via Machine Learning Models

Introduction: Pediatric immune thrombocytopenia (ITP) is the most common acquired bleeding disorder of childhood with 3-4,000 new cases annually. While most children experience self-resolving disease, 25% go on to have chronic ITP (cITP) with thrombocytopenia persisting beyond one year. Given the likelihood of spontaneous resolution and potential side effects of initial treatments, standard management for patients without severe or life-threatening bleeding is often observation. However, if it were possible to predict development of chronic disease, earlier initiation of long-term therapies could minimize bleeding risk, reduce fatigue, ease activity restrictions, and mitigate the poorer health-related quality of life that characterizes cITP.Though associations between variables and cITP have been reported, none are strong enough alone to dictate clinical decisions regarding ITP management. Machine learning (ML) is a set of statistical tools that can be utilized to make predictions or cluster data from large datasets. ML models are well suited to complex patterns within clinical datasets. ML can incorporate greater numbers of variables than could be used with traditional statistical models and can assess the impact of variables contingent upon the state of multiple other variables. In this study, we used a large clinical dataset to test a series of ML models on their ability to predict cITP development.Methods: Our group identified 696 pediatric ITP patients cared for at Texas Children's Hematology Center (TXCH) from 2012 to 2020. Of these, 332 had confirmed acute ITP (self-resolved disease in <1 year), and 253 were diagnosed with cITP. Demographic information, presenting clinical features, and laboratory data drawn within 1 month of diagnosis were tabulated for this cohort. Variables included age, gender, race, ethnicity, presence of primary ITP (defined as ITP that is not caused by another underlying disorder), presenting platelet count, absolute leukocyte count, absolute lymphocyte count, absolute eosinophil count, immature platelet fraction (IPF), mean platelet volume (MPV), direct antiglobulin test (DAT), anti-nuclear antibody (ANA) titer, and immunoglobulin levels.We tested the capabilities of several ML methods in predicting cITP using these presenting clinical and laboratory parameters. We performed a 10-fold cross validation to compare average performance metrics of a 100 tree random forest method against logistic ridge regression, support vector machine (SVM), naïve bayes, and AdaBoost methods. We tested feature importance of clinical variables with relation to cITP using the Gini index. Cross-validated ML method performance was compared using the area under the curve (AUC) receiver operator curve (ROC), as well as F1 statistic, classification accuracy (CA), precision or positive predictive value, and recall or sensitivity. Analyses was performed using Orange v2.7 (https://orangedatamining.com).Results: The top five most informative clinical features by Gini index were primary ITP, MPV, IPF, absolute lymphocyte count, and ANA titer. Comparing our five ML methods after 10-fold cross validation, the 100 tree random forest model was the top performing method on average (AUC = 0.795, CA = 0.737, F1=0.734, Precision = 0.738, Recall = 0.737). With an AUC of approximately 0.8, there is an 80% chance the model will accurately distinguish cITP from aITP. A close second performing method was the naïve bayes (AUC 0.792, CA = 0.698, F1 = 0.671, Precision = 0.737, Recall = 0.698). We present the average cross validated AUC ROC curves and the full ML method test statistics in Figure 1.Conclusions: Clinical and laboratory features present at the time of initial ITP diagnosis can be utilized to predict the development of cITP in pediatric patients using ML models. Ensemble decision tree methods are promising candidates for further ML method refinement, as AUC ROC of predicting cITP with a 100 tree RF model is > 0.7. Our group is expanding this model through incorporation of genotyping data from both acute and cITP patients. Ultimately, these ML models, in the form of an online tool, could be applied to predict cITP, allowing providers to initiate upfront interventions for those ITP patients who are unlikely to experience spontaneous disease resolution. [Display omitted] DisclosuresKirk: Biomarin: Honoraria. Powers: American Regent: Research Funding. Despotovic: Agios: Consultancy; Apellis: Consultancy; UpToDate: Patents & Royalties: Royalties; Novartis: Consultancy, Research Funding.

Distribution Characteristics of ANA and ANCA in Patients with Hyperthyroidism.

Antinuclear antibody (ANA) and Antineutrophil autoantibodies (ANCA) are often used as markers for the diagnosis of autoimmune diseases. In clinical practice, we have found that ANA and ANCA often occur in sera of patients with hyperthyroidism. The study aimed to discover the positive features of anti-nuclear antibodies (ANA) and anti-neutrophil cytoplasmic antibodies (ANCA) in hyperthyroidism. In sera samples from 171 patients with hyperthyroidism and 50 healthy controls, ANA and ANCA were detected with indirect immunofluorescence (IIF) method. ANA and ANCA positive rates were higher in hyperthyroidism (33.9% and 29.2%, respectively) than those in control (4.0% and 2.0%, respectively); the low titer (≤1:320)of ANA was dominated (86.2%) in 58 hyperthyroidism patients with positive ANA, the major pattern involved homogeneous (48.3%) and speckled patterns (48.3%). The low titer (≤1:32) of ANCA was dominated( 64.6%) in 50ANCA positive samples and the major pattern was perinuclear (p) ANCA (96%). The positive rates of ANA and ANCA were increased and mainly appeared of low titer in hyperthyroidism, which supplement the laboratory characteristics of hyperthyroidism.

75-Year-Old Man With Fever and Malaise

A 75-year-old Caucasian man presented to the emergency department following an episode of unresponsiveness and urinary incontinence. Recent history revealed fever, fatigue, generalized weakness, increased urinary frequency, anorexia, and a 10-lb unintentional weight loss over several months. His medical history was significant for previous exposure to asbestos with pleural calcification; recent painless truncal and upper extremity rash with biopsy, demonstrating weak granular deposition of complement C3 (indeterminate for early connective tissue disease manifestation or normal variant); positive antinuclear antibody (ANA) titer of unknown clinical significance; esophageal stricture treated with dilation; type 2 diabetes mellitus treated with metformin; hypertension treated with amlodipine and enalapril; and hyperlipidemia treated with atorvastatin.

Antinuclear antibodies (ANAs) detected by indirect immunofluorescence (IIF) method in acute COVID-19 infection; future roadmap for laboratory diagnosis

IntroductionAs in other viral infections, anti-nuclear antibodies (ANAs) are observed in SARS-CoV-2 infection. We investigated the presence of autoantibodies in acute COVID-19 and the association with early laboratory findings. Materials and methodsWe examined 50 sera (>18 years, 25 Female) from patients with acute COVID-19. ANAs (HEp-20-10 liver biochip), anti-neutrophil cytoplasmic antibody (ANCA, Europlus Granulocyte Mosaic 32) and anti-double stranded DNA were investigated with product of Euroimmune AG (Luebeck, Germany) by indirect immunofluorescence (IIF) method. Also, antibody against cyclic citrullinated peptide (anti-CCP) was examined by a chemiluminisens assay (Euroimmun AG, Luebeck, Germany). Samples from 50 blood bank donors collected before the COVID-19 pandemic were used as controls. ResultsThe IIF-ANA test was positive in 18% (N = 9/50) of the patients. The median time of sample collection was 7 days (range: 1–28 days) after diagnosis. ANA was positive in only one (2%) control sample. Five (55.5%) patients were ANA positive with a strong titer (3+). There was no relationship between antibody titration and time of sample collection (p = 0,55). Anti-CCP was detected in a nucleolar (3+) positive patient (2%). ANA was detected in 14.28% (N = 1/7, rods-rings (±), p = 0,78) of patients in the intensive care unit(ICU). Patients treated in the clinic have more and higher titers of ANA, mostly in nucleolar patterns, than ICU patients. ConclusionsThe variety of antibodies detected in acute COVID-19 and the uncertainty of how long they persist can lead to confusion, especially in the diagnosis of systemic autoimmune rheumatic diseases for IIF-ANA testing in immunology laboratories. Improvements in cell lines and methods will facilitate the diagnostic process.

Характеристика когнітивної дисфункції у хворих на системний червоний вовчак

The purpose of the study was to explore the structure of cognitive impairment in patients with systemic lupus erythematosus and to determine the factors associated with its development. Materials and methods. Advanced examination of 64 patients with systemic lupus erythematosus was carried out. Neurological disorders were diagnosed in 54 patients (84.38% of patients). These patients were included in the main study group (group 1). In 10 (15.62% of patients) patients, these manifestations were not found and they entered the control group (group 2). The object of the study was cognitive impairment in patients with systemic lupus erythematosus. To assess the cognitive status of patients, the Montreal Cognitive Assessment Scale was used, a widely used questionnaire that evaluates cognitive functions across multiple domains. The laboratory study included blood tests to identify the type and titer of antinuclear antibodies, lupus anticoagulant, and antiphospholipid antibodies, in particular, anti-cardiolipin antibodies. Results and discussion. It was found that the complaints that patients usually present to describe impaired cognitive functions (such as "memory deterioration", "memory impairment", "decreased attention", "difficulty concentrating", etc.) were among the most common in patients with systemic lupus erythematosus. Thus, complaints of memory impairments were expressed by 37 patients (57.81% CI 45.71-69.91), impaired attention and concentration – 41 patients (64.06% CI 52.31-75.82), and between these complaints a strong correlation was established (r = 0.83; p &lt;0.001). The results of the examination of patients using the Montreal Cognitive Assessment Scale showed that the average indicator among all examined is 25.0 (22.0; 27.5) points in the main group – 24.0 (22.0; 26.0) points, which is statistically significantly less (p &lt;0.001) compared with the control group – 28.0 (27.0; 29.0) points. It was found that among patients who scored less than 26 points on the Montreal Cognitive Assessment Scale, there was a statistically significant decrease in indicators in the domains of memory, attention, and speech (p &lt;0.001). It was found that there is a correlation between the presence of anti-cardiolipin antibodies with CD (determined by the Montreal Cognitive Assessment Scale) (rs = -0.56; p &lt;0.001), the same correlation was found in relation to lupus anticoagulant (rs = -0.56; p &lt;0.001). Conclusion. Cognitive dysfunction is one of the most common neurological manifestations of systemic lupus erythematosus. Among the examined patients, decrease in indicators in the domains of memory, attention and speech is the most often observed. Cognitive dysfunction may be associated with the production of certain classes of autoantibodies: antiphospholipid antibodies (in particular, anti-cardiolipin antibodies) and lupus anticoagulant

Metabolic Acidosis and Hyponatremia in a Patient With Metastatic Melanoma

Metabolic Acidosis and Hyponatremia in a Patient With Metastatic Melanoma

P04 Primary mediastinal large B-cell lymphoma in a Caucasian female with anti-SAE-1 positive dermatomyositis

Abstract Case report - Introduction This is a case of a female patient who was diagnosed with dermatomyositis with anti-Small ubiquitin-like modifier Activating Enzyme-1 (SAE-1) and anti-Ro52 autoantibodies. She had extensive skin involvement with mild extracutaneous features and responded well to a combination of prednisolone, hydroxychloroquine and azathioprine. She subsequently developed primary mediastinal large B-cell lymphoma about 3 years after diagnosis of dermatomyositis. Case report - Case description A 59-year-old Caucasian female presented in January 2018 to the dermatologist with a 6-month history of itchy, dry, flaky skin around her eyes with periorbital erythema which later progressed to fixed periorbital oedema. At that point, a diagnostic biopsy was taken from the left lower eyelid which showed a deep inflammatory infiltrate with significant oedema and dilated blood vessels. A few weeks later, she developed a widespread erythematous rash. Other than some cramps and myalgia in the thighs, there was no muscle weakness or dysphagia. There were no red flag symptoms, but some dry cough without dyspnoea. Clinical examination revealed periungual erythema, periorbital erythema and oedema, widespread erythematous eruption on the torso and limbs and papular eruptions on the hand dorsum. Muscle power in upper and lower limbs scored 5 in the MRC scale. Blood tests showed slight lymphopaenia, antinuclear antibodies titre 1:400, dsDNA and ENA negative, raised IgG kappa monoclonal protein at 10g/L with normal kappa/lambda ratio, creatine kinase initially 93 that later rose to 209, slightly raised lactate dehydrogenase 262, otherwise unremarkable biochemistry and inflammatory markers. Extended myositis screen with immunoblot revealed positive SAE-1 and anti-Ro52 autoantibodies. MRI of the femurs showed mild oedema in the adductors. Electromyogram showed some myopathic motor units, not florid but convincingly present. Computed tomography of neck, thorax, abdomen and pelvis did not reveal any underlying malignancy at the time. The diagnosis of SAE-1-positive dermatomyositis was made and she was treated with high-dose prednisolone (1mg/kg), azathioprine and hydroxychloroquine with good response and dermatomyositis went into remission. In December 2020, she developed dyspnoea and was found to have left-sided pleural effusion and anterior mediastinal mass, a biopsy of which confirmed primary mediastinal large B-cell lymphoma. She is currently receiving chemotherapy with rituximab-cyclophosphamide-doxorubicin-vincristine-prednisolone and azathioprine was discontinued. Her dermatomyositis remains in remission. Case report - Discussion The SAE-1 autoantibody was first identified in 2007. Its prevalence ranges from 1% to 8% in different cohorts. The main clinical feature of anti-SAE-1-positive disease tends to be a widespread cutaneous involvement which is typically pruritic, either amyopathic or associated with mild muscle involvement. Other extracutaneous manifestations include arthralgia, dysphagia and interstitial lung disease (ILD) with variable frequency in different cohorts. ILD is usually milder than in other amyopathic dermatomyositis subgroups. Our patient presented with rather extensive cutaneous disease (clinical photography available) requiring high-dose prednisolone and we decided to add azathioprine as a steroid-sparing agent. She had minimal muscle disease and no other extracutaneous manifestations. Interestingly, she developed lymphoma 3 years following the diagnosis of dermatomyositis. The association between dermatomyositis and malignancy is well-established. The generally accepted definition of cancer-associated myositis is malignancy within 3 years of disease onset. Dermatomyositis as opposed to polymyositis, increasing age, male sex, dysphagia, cutaneous ulceration and the presence of anti-transcription intermediary factor-1 gamma antibodies (TIF1γ) were all associated with increased cancer risk in a recent meta-analysis by Oldroyd et al. Anti-SAE-1 is variably reported to be associated with cancers. A recently published study of a North American cohort of anti-SAE-1-positive dermatomyositis patients reported five cases of cancers, mainly internal malignancies and one case of B-cell lymphoproliferative disorder. We are not aware of any more reported cases of lymphoma in patients with anti-SAE-1 autoantibodies. A 2018 study did report two cases of dermatomyositis patients who developed lymphoma without specifying the autoantibody profile in those patients. Our case contributes to the fact that dermatomyositis can be associated with malignancies. It also raises awareness that this rare subgroup of dermatomyositis with SAE-1 autoantibodies can be associated with lymphoma. However, this association has not been widely reported in the literature. Case report - Key learning points