Antinuclear Antibody Test Research Articles

Navigating into the Dental Management of a Child with Morphea: A Case Report

Morphea, a morphological variant of Localised Scleroderma (LoS) that typically occurs in children, is an inflammatory disease of connective tissue leading to skin and underlying tissue sclerosis due to increased deposition of collagen. The aetiology of morphea is quite elusive. Morphea, along with other regions also affects oral and perioral tissues; the most common affected implication being facial skin and tongue rigidity. The author reports a case of a 10-year-old female who reported to the Department of Paediatric and Preventive Dentistry for retained maxillary anterior deciduous teeth. The patient also presented with scarring on her face, chest, and arms. Her lips were thin, rigid and partially fixed producing microstomia with decreased mouth opening. Clinical examination, blood tests, Contrast-Enhanced Computed Tomography/High-Resolution Computed Tomography (CECT/ HRCT) of thorax, Antinuclear Antibody (ANA) test, Antineutrophilic Cytoplasmic Antibody (ANCA) Test, Anti-dsDNA Test, systemic sclerosis/myositis profile, and histopathological evaluation confirmed the diagnosis of morphea. The management of morphea is multidisciplinary. Hence, the role of a paediatric dental surgeon in recognising the development of disease progression in a patient and avoiding any oral complications is very important.

Demographics and clinical manifestations of lupus patients: experience from a private hospital in Saudi Arabia

Background: Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by a chronic pattern of relapses and remissions, with variable presentations ranging from mild skin manifestations to severe, life-threatening illness. The disease is multisystematic, with the most severe complications related to the kidneys and nervous system. Among the SLE manifestations, lupus nephritis is common, observable in approximately 40% of SLE patients. This study, conducted at a private hospital in Saudi Arabia, aimed to evaluate the demographic characteristics, clinical presentations, and laboratory results of patients with SLE. Methods: This retrospective study involved 105 SLE patients who were seen in the rheumatology clinic at the Specialized Medical Center in Riyadh from 2007 to 2022. The medical records of the patients were reviewed for patient demographics, clinical and serological characteristics, and therapeutic data. Results: The largest proportion (34.3%) was aged between 31 and 40 years. Female dominancy was found, as females represented 91 patients (86.7%). Joint involvement was found to be the most affected organ in the majority of the patients, accounting for 80 patients (76.2%), while the least affected organ was the heart, with cardiac manifestations present in 7 patients (6.7%). Conclusion: The majority of patients (95.2%) displayed a positive antinuclear antibody test, and more than one-half of the patients (68.6%) displayed positive anti-double stranded DNA. The most reported medication was hydroxychloroquine in 104 patients (99%), followed by steroids in 89 patients (84.8%).

Role of some Immunological and non-Immunological Parameters in Prognosis and diagnosis of Systemic lupus erythematosus in Iraqi women patients

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by autoantibody's presence in the circulation and involvement of many systems. The current study aims to study the role of some immunological and non-immunological parameters in SLE development and to illustrate the correlations between these parameters. The current study included 50 blood samples collected from SLE patients and apparently healthy control. The methods of work included Complete Blood Count (CBC) analysis to assess blood components, you mean to analyse Hb, WBC, ESR, ELISA technique to measure serum levels of TLR-7, IL-17, and TNF-γ, antinuclear antibody test (ANA) and double-strand DNA antibody (anti ds DNA). The study results showed a significant increase in serum levels of each WBC (p< 0.005), ESR (p< 0.001), IL17(p< 0.004), TLR7(p< 0.005), IFN-γ (p< 0.001), ANA (p< 0.001), and anti dsDNA (p< 0.001) in SLE patients compared to apparently healthy control but the Hb is decreasing level was low in the SLE patients compared with control. In conclusion, the low hemoglobin, WBC, and ESR are non-specific parameters associated with SLE pathogenesis. ANA, Anti-ds-DNA as excellent biomarkers for the diagnosis of SLE and serum level of TLR-7, TNF-γ, and IL-17 were evaluated in SLE patients compared to healthy people and they may be suggested as a prognostic tool in SLE patients.

Programmable Gravity Self-Driven Microfluidic Chip for Point-of-Care Multiplied Immunoassays.

Point-of-care testing (POCT) is experiencing a groundbreaking transformation with microfluidic chips, which offer precise fluid control and manipulation at the microscale. Nevertheless, chip design or operation for existing platforms is rather cumbersome, with some even heavily depending on external drivers or devices, impeding their broader utilization. This study develops a unique programmable gravity self-driven microfluidic chip (PGSMC) capable of simultaneous multi-reagent sequential release, multi-target analysis, and multi-chip operation. All necessary reagents are introduced in a single step, and the process is initiated simply by flipping the PGSMC vertically, eliminating the need for additional steps or devices. Additionally, it demonstrates successful immunoassays in less than 60 min for antinuclear antibodies testing, compared to more than 120 min by traditional methods. Assessment using 25 clinically diagnosed cases showcases remarkable sensitivity (96%), specificity (100%), and accuracy (99%). These outcomes underscored its potential as a promising platform for POCT with high accuracy, speed, and reliability, highlighting its capability for automated fluid control.

Evans Syndrome in a Patient with Auto Immune Thyroiditis – A Rare Association

A 46-year-old woman, diagnosed with hypothyroidism, was on treatment with synthetic thyroxine 100 micrograms per day for one year. She complained of recent-onset exertional dyspnoea, and had malaise, lethargy, and pica. Investigations revealed significant anaemia and severe thrombocytopenia, necessitating blood transfusion. She had Coombs-positive autoimmune haemolytic anaemia and immune thrombocytopenic purpura, confirming a diagnosis of Evans syndrome. She also had a positive antinuclear antibody test but had no other notable findings of autoimmune disease, suggesting a diagnosis of primary Evans syndrome. The patient was treated with intravenous dexamethasone for four days, followed by oral prednisolone at 1mg/kg/ day, with supplemental calcium and vitamin D. Thyroperoxidase antibody was positive and there was reduced uptake in thyroid scintigraphy, confirming a diagnosis of autoimmune thyroiditis. Hashimoto’s thyroiditis frequently coexists with non-endocrine autoimmune disorders. Presence of antithyroid antibodies is sometimes observed in Evans syndrome, a condition where there is simultaneous occurrence of autoimmune Haemolytic Anaemia, Cytopoenia and immune thrombocytopenic purpura. However, the development of Evans syndrome in patients with overt hypothyroidism and Hashimoto’s thyroiditis is rare. This case implies the potential existence of a shared immunogenetic pathway among three distinct autoimmune diseases, namely autoimmune haemolytic anemia, immune thrombocytopenic purpura, and Hashimoto’s thyroiditis, in the pathogenesis.

Prevalence and sociodemographic correlates of antinuclear antibody testing by indirect immunofluorescence or solid-phase assays in a Spanish population: the Camargo Cohort

Autoantibodies are the hallmark of autoimmunity, and specifically, antinuclear antibodies (ANA) are one of the most relevant antibodies present in systemic autoimmune diseases (AID). In the present study, we evaluate the relationship between ANA and sociodemographic and biobehavioral factors in a population with a low pre-test probability for systemic AID. ANA were determined in serum samples at baseline visit from 2997 participants from the Camargo Cohort using indirect immunofluorescence assay, and two solid phase assays (SPA), addressable laser bead immunoassay, and fluorescence enzyme immunoassay. Sociodemographic and biobehavioral features of the subjects were obtained at baseline visit using a structured questionnaire. The prevalence of ANA positive results was significantly higher when indirect immunofluorescence assay was used as screening method in comparison with SPAs, being higher in females, older subjects, and those with higher C-reactive protein levels. Considering biobehavioral features, the prevalence was higher in those individuals with a sedentary lifestyle, and in ex- and non-alcohol users. Moreover, considering the relevance of the antibody load using ANA Screen, the prevalence of the antibody load also increased with age, especially in females. In conclusion, the prevalence of ANA varies depending on sociodemographic and biobehavioral features of the subjects, which could be relevant specifically in a population with a low pre-test probability for systemic AIDs.

Modified YOLO network model for metaphase cell detection in antinuclear antibody images

The antinuclear antibody (ANA) test plays the role of screening, diagnosis, treatment and prognosis for autoimmune diseases. However, the ANA test is time-consuming, and strongly depends on the interpretation of experienced medical examiners. With the rise of artificial intelligence, a lot of convolutional neural networks (CNN) have been used to recognize the features of ANA images, such as GoogLeNet, ResNet, and MobileNet. By extracting the disease-related features from the entire ANA image, these models achieve acceptable accuracy, but none of them can replace the manual ANA test completely. This is because they ignore the key features of ANA images. Accordingly, this paper aims to design an object detection model that can directly identify the key features of ANA images, i.e., the Metaphase cells. This process is critical in the manual ANA test performed by the medical examiners. Based on the YOLO model, our design first applies various image preprocessing and data augmentation techniques to enhance the critical features in the training data. We modify the original YOLO model, in which the residual block is replaced with SENet module to improve the classification performance by emphasizing critical features and reducing the influence of low-level features. Moreover, we use the different activation function to prevent the modified model from partial judgment. The experimental results show that our design can effectively improve the performance of ANA metaphase identification. Compared to the related CNN models, our design can improve F1-score and mAP by range 5%–14% and 11%–13%, respectively. In particular, the Kappa value of our design is 0.82 that is almost perfect agreement with the ANA experts.

Systemic lupus erythematosus associated with HIV infection: a retrospective case-control study.

The association of systemic lupus erythematosus (SLE) and human immunodeficiency virus (HIV) remains scarcely described in the literature. Our objectives were to describe the characteristics of SLE in patients living with HIV (SLE-PLHIV) and compare it with SLE characteristics in patients without HIV infection. We performed a retrospective study of 13 patients with SLE-PLHIV diagnosed between 1975 and 2020 in four different French hospitals. These patients were compared in a case-control study with a 1:5 ratio to age-, sex- and year of diagnosis- matched patients with SLE without HIV infection. Median (IQR) age at SLE diagnosis for patients with SLE and HIV infection was 43 years (36-53). There were 77% women. Main clinical manifestations were polyarthrtitis (84%), cutaneous lupus (69%), kidney disease (54%), serositis (15%) and autoimmune cytopenias (auto-immune haemolytic anaemia and/or immune thrombocytopenia) (31%). There were no neuropsychiatric manifestations. All patients had positive antinuclear antibody test with a titre ≥1:160. Anti-dsDNA antibodies were present in 75% of patients, and anti-Sm antibodies in 33%. SLE-PLHIV had more frequently renal manifestations (54 vs. 16%, p=0.006) and autoimmune cytopenia (31 vs 8%, p=0.04) than patients without HIV infection. SLE and HIV infection appear to be a rare association. Patients with SLE-PLHIV seem to have more renal manifestations and autoimmune cytopenias than patients with SLE without HIV infection.

Harmonization of ANA testing challenge: quantification strategy to accurately predict end-point titers avoiding serial dilution.

Despite the advantages of automated systems for antinuclear antibody (ANA) analysis, the prediction of end-point titers avoiding serial dilutions is still in progress. The aims of this study were to set a conversion table providing discriminant ranges of fluorescence signal intensity values (FI) corresponding to the end-point titers and validate this tool in a real-life laboratory setting. Eight hundred ninety-four serum samples were analyzed for ANA using Image Navigator System. In order to classify FI into non-overlapping groups corresponding to conventional end-point titers, statistical discriminant analysis was used. Validation study was performed calculating agreement and error rates between visual readings and conversion table of 1119 routine ANA positive samples. Setting of FI ranges corresponding to the end-point titers for different staining patterns was computed. For samples showing single pattern, the overall agreement between visual readings and conversion table was 98.4% for all titers ranging from 1:160 to 1:2560, of which 68.0% had the same titer and 30.4% were within ± one titer difference. Concordance rates according to ANA patterns were as follows: (1) nuclear 98.4%, of which 67.0% had the same titer and 31.4% ± one titer; (2) cytoplasmic 100%, of which 72.7% had the same titer and 27.3% than ± one titer; (3) mitotic 66.6%, of which 33.3% had more ± one titer. Our study developed a quantification method for autoantibodies titers assessment based on just one single sample dilution instead of traditional serial dilution approach, providing significant advantages in routine laboratory in terms of reduction in hand-on time and harmonization of results.

Five-Year Analysis of Anti-Nuclear Antibody (ANA) and Extractable Nuclear Antigen Antibody (anti-ENA) Immunoblot Test Results

Autoimmune disorders may cause systemic disease in which multiple organs are affected or may also be localized as single-organ involvement. Various ancillary immunological tests used in cases where systemic involvement is observed, and differential diagnosis becomes difficult or non-specific symptoms are observed. For this purpose, investigation of antinuclear antibodies (ANA) and antibodies against extractable nuclear antigens (ENA) in patient serums using various methods is a guide for clinicians. In this study, we aimed to evaluate the effectiveness of ANA and ENA antibody tests by examining the test results, the patients’ demographic data, and the clinics that ordered the tests. In the study, a retrospective review of the results of 37,791 ANA tests studied on serum samples sent to the medical microbiology laboratory of our hospital from various clinics between January 2018 and December 2022 is presented. ANA tests were resulted semi-quantitatively by evaluating the slides prepared using diluted serum samples at a ratio of 1:100 and HEp-2 cells and monkey liver tissue under a fluorescent microscope with the indirect immunofluorescence (IIF) antibody method. Of the patients who requested ANA test, 11,604 (30.7%) were male and 26,187 (69.3%) were female. The mean ages were 43.46 (0-94) and 46.94 (0-96), respectively. Of the samples tested, 18.8% (7,107/37,791) were evaluated as ANA positive. The ANA positivity rate was significantly higher in women (24.8%) than in men (19.7%) (p<0.001). ANA positive samples were re-tested using the anti-ENA immunoblot method. Of the 7,107 ANA-positive patients, 3,809 (53.6%) were found to be anti-ENA positive for at least one specific antibody, while 3,298 (46.4%) were negative. In the anti-ENA profile, antibodies against 11 different antigen types were screened and the most frequently detected antibody was anti-SS-A (22.7%), and this was followed by anti-centromere (12.8%), anti-RNP (10.2%), and anti-dsDNA (9.7%) antibodies. Immunoblot-based anti-ENA tests provide specific information for the diagnosis of autoimmune diseases. In our study, the fact that anti-ENA tests were negative in a significant part of ANA positive patients indicates the inadequacy of the immunoblot test panel and reveals the need for immunoblot tests with wider antibody diversity or any alternative methods.

B-131 The Prevalence and Clinical Relevance of the DFS Immunofluorescent Staining Pattern in a Large ANA-positive Cohort

Abstract Background The dense fine-speckled (DFS) nuclear pattern is one of the most common indirect immunofluorescence (IIF) patterns detected during routine antinuclear antibody (ANA) screening. Although various researchers have studied the DFS pattern in recent years, it presents a clinical puzzle since its significance remains elusive. Anti-DFS-70 antibodies occur in healthy individuals with different medical conditions. Unlike the other ANA patterns, they are not associated with systemic autoimmune disease. The present study examined the association of a DFS ANA pattern with the medical conditions of patients who presented to a tertiary care medical center. Methods Retrospective chart review of all laboratory values (January 2020 through June 2022) with ANA- and DFS-positive patterns in patients with ANA tests ordered by various clinicians and compared to the patient diagnosis reported. UMass Human IRB approves this study. Results Of 8885 ANA samples analyzed, 67.8% (6022) were reported negative. Of total positive ANA (2863) samples, 78.6% (2257) had nuclear patterns, 9.1% (260) had mitotic patterns, and 12.1% (346) had cytoplasmic patterns. Of the positive ANA samples, 14.6% (417) had DFS patterns. For samples with DFS pattern, titers ranged from 1:40 to 1:1280; 62.5% were between1:40, and 1:80. Of samples positive for ANA DFS patterns, 76% (317) were from female patients, and 90% (375) were from patients >21 years of age. Among patients with DFS patterns, the most commonly reported diseases were neurological, followed by respiratory, digestive, circulatory, and musculoskeletal (Table 1). Conclusion Clinicians should use a positive ANA with a DFS pattern to indicate pathological phenomena other than autoimmune diseases. Only 3.1% of the patients with DFS patterns have a systemic rheumatic disorder. Clinicians should pay close attention to ANA Patterns, especially DFS staining when using ANA testing.

A Review of Systemic Autoimmune Rheumatic Diseases and Analysis of Antinuclear Antibody Testing Methods and Clinical Utility of EliA CTD Screen

A Review of Systemic Autoimmune Rheumatic Diseases and Analysis of Antinuclear Antibody Testing Methods and Clinical Utility of EliA CTD Screen

Chronic False Positive Rapid Plasma Reagin (RPR) Tests Induced by COVID-19 Vaccination

False positive reactive plasmin reagin (RPR) reactivity following a COVID-19 vaccine has been reported, and it is therefore conceivable that individuals who receive frequent coronavirus disease 2019 (COVID-19) vaccinations may exhibit durable RPR responses. Here, we sought to investigate the extent to which repeated mRNA COVID-19 vaccines can elicit chronic false RPR reactivity in a longitudinal cohort. Participants (n = 119) in an IRB-approved (#20201026), longitudinal SARS-CoV-2 cohort study were screened for RPR reactivity via manual RPR card assays. Samples with reactive results underwent additional testing, including follow-on RPR screening at additional timepoints, confirmatory fluorescent treponemal antibody (FTA-ABS) testing and anti-nuclear antibody (ANA) testing. Medical histories were collected. We observed (n = 2) screen-positive RPR results (1.7% [2/119]) following booster vaccination, for which two individuals exhibited chronic, vaccine-induced RPR reactivity for up to 9 months following booster vaccination. Both participants were ANA-negative. It is imperative for clinicians to be mindful of the potential immunologic interference of COVID-19 vaccines with standard infectious disease assays, including RPR testing. Detailed medical histories and clinical contexts, including recent vaccination, should be reviewed prior to proceeding with distressing and invasive workups.

Evaluation of Uveitis Induced in Rats by a Type I Collagen Peptide as a Model for Childhood Arthritis-associated Uveitis.

Chronic asymptomatic and acute symptomatic anterior uveitis are forms of ocular inflammation associated with juvenile idiopathic arthritis (JIA) Chronic JIA-associated uveitis is characterized by young age of onset, female predilection, oligoarthritis, and antinuclear antibody (ANA) positivity. Acute JIA-associated uveitis predominantly affects older male juveniles who also develop enthesitis. A type I collagen-derived peptide (melanin-associated antigen [MAA]) induces anterior uveitis in rodents. In this study, we evaluated MAA-induced uveitis in rats as a potential model for JIA-uveitis. We characterized MAA-induced uveitis by assessing its relationship to age and sex; tracking the occurrence of arthritis, enthesitis, and ANA positivity; and measuring vitreous fluid inflammatory biomarkers. Juvenile and adult and male and female Lewis rats (Rattus norvegicus) were inoculated with MAA. Slit-lamp biomicroscopy, indirect ophthalmoscopy, and joint examinations were performed 3 times weekly. Rats were euthanized at 4 wk after MAA inoculation, and plasma ANA testing, vitreous inflammatory biomarker assays, and globe histopathology assessments were conducted. Uveitis, arthritis, ANA status, levels of inflammatory biomarkers, histopathology, and joint tomographic images were assessed in relation to age and sex and compared with nonuveitic controls. All MAA-immunized rats developed uveitis characterized by anterior chamber fibrin, iridal vessel dilation, and miosis, and uveal and choroidal lymphocytic infiltration. Levels of the vitreous fluid biomarker CCL5 were higher in uveitic rats compared with control rats. Time to uveitis onset, clinical uveitis scores, and biomarker levels did not differ based on age or sex. None of the MAA-exposed rats had arthritis, enthesitis, or ANA. None of the rats inoculated with MAA that had been treated with matrix metallopeptidase 1 had clinical, histologic, or immunohistochemical evidence of ocular inflammation. In contrast to JIA-associated uveitis in humans, MAA-induced uveitis in rats is not associated with age or sex predilections and MAA is not arthritogenic.

Clinical Performance of the Line Immunoassay, Digital Liquid Chip Method, and Chemiluminescent Immunoassay for Detecting Specific Antinuclear Antibodies.

Antinuclear antibodies (ANAs) against certain antigens are useful for identifying autoimmune disorders. Although new solid phase-based immunoassays have been developed for evaluating ANAs, the conventional line immunoassay (LIA) is commonly used in clinical practice. To compare the clinical performance of 2 newly developed methods for detecting specific ANAs with LIA. Six hundred ninety-six serum samples were collected from 559 patients with autoimmune disease (AID) and 137 controls. The samples were screened by using the LIA, digital liquid chip method (DLCM), and chemiluminescent immunoassay (CLIA) for specific ANAs. The agreement across assays and the clinical performance of each assay in diagnosing ANA-associated rheumatic diseases (AARDs) were evaluated. Almost perfect agreement was observed among all assays for anti-centromere protein B (κ = 0.85-0.97), anti-ribosome P (κ = 0.85-0.88), anti-SSA 52 (κ = 0.86-0.89), and anti-SSA 60 (κ = 0.89-0.91); moderate to substantial agreement was detected for the autoantibodies against Sm, Jo-1, ribonucleoprotein, Scl-70, and SSB (κ = 0.55-0.80). LIA exhibited better sensitivity for diagnosing AARDs, while DLCM and CLIA demonstrated higher specificity. In the subset of AIDs, especially systemic lupus erythematosus, antibody positive percentages varied greatly between assays. The 3 assays showed comparable qualitative agreement; however, the standardization of testing for ANAs remains challenging owing to intermanufacturer variations. Moreover, DLCM and CLIA exhibited better specificity in distinguishing non-AID individuals, whereas LIA was more sensitive in diagnosing AARDs.

Clinical diagnoses associated with a positive antinuclear antibody test in patients with and without autoimmune disease

BackgroundAntinuclear antibodies (ANA) are antibodies present in several autoimmune disorders. However, a large proportion of the general population (20%) also have a positive test; very few of these individuals will develop an autoimmune disease, and the clinical impact of a positive ANA in them is not known. Thus, we test the hypothesis that ANA + test reflects a state of immune dysregulation that alters risk for some clinical disorders in individuals without an autoimmune disease.MethodsWe performed high throughput association analyses in a case–control study using real world data from the de-identified electronic health record (EHR) system from Vanderbilt University Medical Center.The study population included individuals with an ANA titer ≥ 1:80 at any time (ANA +) and those with negative results (ANA-). The cohort was stratified into sub-cohorts of individuals with and without an autoimmune disease. A phenome-wide association study (PheWAS) adjusted by sex, year of birth, race, and length of follow-up was performed in the study cohort and in the sub-cohorts. As secondary analyses, only clinical diagnoses after ANA testing were included in the analyses.ResultsThe cohort included 70,043 individuals: 49,546 without and 20,497 with an autoimmune disease, 26,579 were ANA + and 43,464 ANA-. In the study cohort and the sub-cohort with autoimmune disease, ANA + was associated (P ≤ 5 × 10–5) with 88 and 136 clinical diagnoses respectively, including lupus (OR ≥ 5.4, P ≤ 7.8 × 10–202) and other autoimmune diseases and complications. In the sub-cohort without autoimmune diseases, ANA + was associated with increased risk of Raynaud’s syndrome (OR ≥ 2.1) and alveolar/perialveolar-related pneumopathies (OR ≥ 1.4) and decreased risk of hepatitis C, tobacco use disorders, mood disorders, convulsions, fever of unknown origin, and substance abuse disorders (OR ≤ 0.8). Analyses including only diagnoses after ANA testing yielded similar results.ConclusionA positive ANA test, in addition to known associations with autoimmune diseases, Raynaud’s phenomenon, and idiopathic fibrosing alveolitis related disorders, is associated with decreased prevalence of several non-autoimmune diseases.

Choosing Wisely: The Canadian Rheumatology Association Pediatric Committee's List of Items Physicians and Patients Should Question.

To develop a list of tests or treatments frequently used in pediatric rheumatology practice which may be unnecessary based on existing evidence. A Choosing Wisely (CW) Working Group composed of 16 pediatric rheumatologists, one allied health practitioner, one parent, and one patient used the Delphi method to generate, rank, and refine a list of tests and treatments that may be unnecessary or harmful. The items with the highest content agreement and perceived impact were presented in a survey to all Canadian Rheumatology Association (CRA) physicians who practice pediatric rheumatology. Respondents were asked to rate their agreement, impact, and rank the items. Five items with the highest composite scores and two additional items selected by the CW Working Group were put forward for literature review. The initial Delphi procedure generated 80 items. After three rounds, the list was narrowed to 13 items. The survey was completed by 41/81 (51%) CRA pediatric members across Canada. Respondent characteristics were similar to the CRA pediatric membership for gender, geographical location, and career stage. The highest composite score items were anti-nuclear antibody testing, drug toxicity monitoring, human leukocyte antigen-B27 testing, rheumatoid factor/anti-cyclic citrullinated peptide testing, and Lyme serology testing. Two additional items (numerous or repeated intra-articular corticosteroid injections, and autoinflammatory diseases genetic testing) were also selected. Literature review was performed for these seven highest priority items. We have identified areas for quality improvement in the evaluation and treatment of rheumatic diseases in Canadian children.

Choosing Wisely in Immunology Laboratory: Reviewing of Antinuclear Antibody (ANA) Test Requests and Results Together with Other Tests

In this study, it was aimed to examine the distribution and positivity rates of the tests reported in the medical immunology laboratory of a tertiary education and research hospital, and to determine the distribution of antinuclear antibody (ANA) test requests, which constitute a significant part of the workload, according to disease diagnosis/preliminary diagnoses and clinical departments, and to examine the possible causes and costs of incorrect-inappropriate test orders, and to consider effective and applicable solution suggestions. In the study, a retrospective review of data on all immunoserology tests (n=94,954 individual parameters) reported approximately over a three-year period starting from September 2016 was presented. When the tests are divided into three main groups; among all test parameters, ANA tests ranked first with a rate of 20.3% (n=19,248). In our study, the positivity rate of ANA tests evaluated by the indirect immunofluorescence antibody (IFA) method was found as 23.1% (n=4,446). The number of reported parameters of specific autoantibody tests (second group), which include many different tests (IFA, ELISA, and immunoblot based), was 67,976, and the overall positivity was 2.96%, varies between 0.8% and 12.7%, depending on the antibody type. In the ELISA-based brucella and antiviral (herpes simplex virus 1 and 2, varicella virus, measles virus, mumps virus, parvovirus B19) IgM and IgG antibody tests in the third group, the highest positivity rate was observed according to the number of tests requested (30.1%, 2,324/7,730). In ANA-positive patients, the most frequently detected ANA-related autoantibodies were anti-dsDNA (9.2%) and anti-SS-A (8.2%). In ANA-negative patients, in simultaneously ordered tests, anti-dsDNA positivity was found to be 3.3%, while positivity rates for other ANA-related specific autoantibodies were in the range of 0.0-0.31%. ANA tests were most frequently ordered from the rheumatology department (34.2%), and also the highest ANA positivity rate (28%) was observed in this unit. The most notable reason for unnecessary test ordering was the test requests by different physicians for the same patient. We consider that evaluation of ANA tests at a dilution of 1:100 may lead to unnecessary second-step testing (specific autoantibodies) due to the low positive results, and that narrow-scope second-step autoantibody test panels will have negative effects on laboratory efficiency.

Antinuclear antibody (ANA) testing in primary care. The test is positive what now? A two-phase observational study of UK primary care.

The ANA-associated diseases are rare autoimmune diseases (including Systemic lupus erythematosus [SLE], Sjögren's, Scleroderma, autoimmune hepatitis). Interpretation of ANA-tests is difficult, it is frequently positive in patients who do not appear to have an associated disease. In those who are ANA-positive we suspect there are features that can help distinguish those who will later develop disease. To understand the characteristics of those tested, and in those who have positive features associated with disease development. Two phase study: 1) A case control study to examine characteristics of those tested. Cases defined as having had an ANA-test performed regardless of result, matched to controls who have never had an ANA test. 2) A cohort study of ANA-tested cases. In those who are ANA-positive, exposures (from literature, clinicians, and patients) will be used to predict the outcome ANA-associated disease. Phase 2: 888,179 patients have at least one ANA-test performed: positive 22,587 (2.54%), negative 21,908 (2.47%), unknown 843,684 (94.99%).ANA-tested cohort. HR if positive: ANA-disease 5.15 (4.89 to 5.43); All-cause mortality 1.20 (1.16 to 1.24); CV mortality 1.20 (1.14 to 1.27) (adjusted HR (95% CI)).ANA-positive cohort. At 3 years 10.0% (9.7 to 10.5%) and at 20 year 15.7% (16.5 to 14.9% (95% CI) develop ANA-associated disease. HR for Female 2.29 (1.96 to 2.68); <55 years 1.53 (1.37 to 1.71) (adjusted HR (95% CI). Defining the test result is difficult. However, there is clear differentiation between the positive and negative/unknown cohorts. Positive-test status is associated with ANA-disease development and mortality. If ANA-positive, most of those who will develop disease are diagnosed soon after testing; male gender and advanced-age reduce the risk of ANA-diseases.

Prediction of a Positive ANA Result for a Rheumatological Diagnosis in an Outpatient Setting

Objective: To study the predictive value of a positive anti-nuclear antibody (ANA) for a rheumatological diagnosis in an outpatient setting. Methods: Individuals who were referred to the rheumatology outpatient clinics because of a positive ANA between July 2014 and June 2015 were retrospectively reviewed. Presenting symptoms in addition to a positive ANA and whether a final rheumatological diagnosis was made were recorded. The positive predictive value of a positive ANA and its titer for a rheumatological diagnosis, with and without accompanying symptoms was evaluated. Results: A total of 230 patients were included (82% women, age 47.7 ± 14.1 years [range 18-84]). Family medicine and the general outpatient clinic were the main sources of referral (32.2%), followed by ophthalmology (13.0%) and otorhinolaryngology (11.7%). A final rheumatological diagnosis was made in 54 (23.5%) patients, with rheumatoid arthritis being the commonest diagnosis (40.7%). In the absence of any associated symptoms, the predictive value of a positive ANA was 0%. The presence of Raynaud’s phenomenon (100%), joint swelling (59.5%), and joint stiffness (48.9%) predicted a better final rheumatological diagnosis along with a positive ANA. ANA titers of 1:80 or less had a low sensitivity for rheumatic diseases. A receiver operating characteristic (ROC) curve analysis showed that an ANA titer of [Formula: see text]1:128 best predicted a rheumatological diagnosis (AUC 0.78 [0.71–0.85]; sensitivity 0.78; specificity 0.64). Conclusions: To improve the prediction for a rheumatological diagnosis, referral for a positive ANA test should be more appropriately done with compatible symptoms.