Antinuclear Antibody Test Research Articles

Histological evolution of IgG4 related disease

Histological evolution of IgG4 related disease

Presence of autoantibodies and epidemiological characteristics of systemic sclerosis patients in western Paraná

Systemic sclerosis (SSc) is a systemic autoimmune disease of the connective tissue with unknown etiology, characterized by abnormal collagen deposition in the skin. The changes in patients result in the obliteration of microvessels and fibrosis, leading to damage to the skin, gastrointestinal tract, kidneys, lungs, heart, and oral cavity. Brazil has insufficient data about the epidemiological and laboratory aspects of SSc. This study aimed to identify and characterize the patients in treatment for SSc in Cascavel/PR, a city in the south of Brazil. Data were collected from March 2019 to September 2020 from all health services of Cascavel that provide care in rheumatology: a university-affiliated hospital, two public outpatient clinics, and six private clinics. Data about age, sex, residence, time to diagnosis, the form of the disease, and the results of tests for antinuclear (ANA) and anti-extractable nuclear antigens (ENA) antibodies were obtained. The study identified 57 patients; 82.5% were female with a mean age of 50.4 years, and the predominant disease form was diffuse (52.6%). The ANA test was positive in 87.7% of the patients, of which 49.2% showed high titers and a predominance of the centromeric pattern. Anti-Scl-70, anti-centromere (ACA), and anti-RNA polymerase III antibodies were positive in 28.1%, 25%, and 5% of the patients. The characteristics of the patients diagnosed with SSc in Cascavel/PR are similar to those reported in the literature. This study contributed to the scarce Brazilian data about the disease.

Overlap syndrome in a 12-year-old girl with systemic lupus erythematosus and anti-oj antibody-positive polymyositis: a case report

BackgroundThe peculiar presentation of overlap syndrome in children makes precise diagnosis difficult. Children with overlap syndrome may or may not have specific antibodies. We present the case of a 12-year-old girl diagnosed with overlap syndrome of systemic lupus erythematosus (SLE) and juvenile polymyositis (JPM) who tested positive for anti-OJ antibodies.Case presentationWe describe the case of a 12-year-old girl diagnosed with SLE at the age of 7 and presented with fever with malar rash, periungual erythema, generalized weakness, and multiple joint pain at admission. The patient had persistent joint pain and weakness after intravenous methylprednisolone administration and complained of an inability to walk with a positive test for Gower's sign one week after admission, accompanied by elevated alanine aminotransferase (ALT) and creatine-phospho-kinase (CPK) levels. The results of nerve conduction velocity test were normal. Electromyography revealed abundant spontaneous activity and myopathic motor unit action potentials in the right deltoid, biceps, and iliopsoas, in addition to fibrillation and mild myopathic motor unit action potentials in the right rectus femoris muscle. Magnetic resonance imaging revealed diffusely increased signal intensities in the myofascial planes of the bilateral iliopsoas, gluteus, obturator, pectineus, and hamstring muscles. Anti-nuclear antibody, anti-RNP, and rheumatoid factor IgG tests were positive, and inflammatory myopathy autoantibodies revealed anti-OJ antibody positivity, which strongly indicated autoimmune myositis. High-resolution computed tomography of the lung revealed mild pericardial effusion without any evidence of interstitial lung disease. We initiated intravenous pulses of methylprednisolone treatment, followed by cyclosporine, mycophenolate mofetil, and oral steroids. Clinical improvement with a delayed, slowly reduced CPK level after the above treatment and she was discharged after the 18th day of hospitalization.ConclusionOverlap syndrome with inflammatory myositis can occur years later in pediatric SLE cases. We should be alert when patients with SLE develop a new presentation characterized by decreased SLE-specific autoantibody titers, positive anti-RNP antibodies, and elevated CPK. Treatment of the overlap syndrome of SLE and JPM is individualized, and the course differs between pediatric and adult patients.

Antinuclear antibodies in healthy population: Positive association with abnormal tissue metabolism, inflammation and immune dysfunction

Antinuclear antibodies (ANAs) are a spectrum of autoantibodies that react with cell nucleus structures. ANA assay is a screening test for the diagnosis of autoimmune disease. Although many patients with positive ANA did not develop autoimmune diseases, it is unclear whether high concentrations of ANA have potential damage to the body. In this study, we conducted an epidemiological survey of ANAs in healthy population, and further examined the associations of ANA with clinical laboratory indicators, inflammation indicators and immune function indicators in a large health checkup population-based cohort. We found the positive rate of ANA was 7.09%, of which the positive rate of female (10.2%) was higher than that of male (4.6%). Moreover, our data showed that ANA positive population present a higher rate of metabolic abnormalities than control group. We further detected the inflammatory and immune-related indicators of ANA positive population, and found that high ANA was correlated with inflammatory and immune dysfunction. In conclusion, our results indicated that the positive rate of ANA was high in healthy population. Moreover, high levels of ANAmight be involved in the metabolic abnormalities, inflammation and immune dysfunction. Thus, ANA testing should be routine for healthy people, and to avoid misdiagnosis, those who had clinical symptoms should be further examined for the subtype of ANA present in the serum.

Distinct CD4+ T cell signature in ANA-positive young adult patients.

Failure of immune tolerance can lead to autoantibody production resulting in autoimmune diseases, a broad spectrum of organ-specific or systemic disorders. Immune tolerance mechanisms regulate autoreactive T and B cells, yet some lymphocytes escape and promote autoantibody production. CD4+ T cell dysregulation, characterized by decreased or impaired regulatory cells (Tregs) and/or accumulation of memory and effector T cells such as TH17, plays a crucial role in the pathogenesis of these diseases. Antinuclear antibody (ANAs) testing is used as a first step for the diagnosis of autoimmune disorders, although most ANA-positive individuals do not have nor will develop an autoimmune disease. Studying the differences of T cell compartment among healthy blood donors, ANA-negative patients and ANA-positive patients, in which loss of tolerance have not led to autoimmunity, may improve our understanding on how tolerance mechanisms fail. Herein, we report that ANA-positive patients exhibit a distinct distribution of T cell subsets: significantly reduced frequencies of recent thymic emigrants (RTE) and naïve T cells, and significantly increased frequencies of central memory T cells, TH2 and TH17 cells; modulations within the T cell compartment are most profound within the 18-40 year age range. Moreover, CD4+ T cells in ANA-positive patients are metabolically active, as determined by a significant increase in mTORC1 and mTORC2 signals, compared to ANA-negative patients and healthy blood donors. No significant impairment of Treg numbers or pro-inflammatory cytokine production was observed. These results identify a unique T cell signature associated with autoantibody production in the absence of autoimmune disease.

The clinical value of indirect immunofluorescence for screening anti-rods and rings antibodies: A retrospective study of two centers in China.

ObjectiveTo investigate the distribution and clinical significance of the rods and rings (RR) pattern in various diseases.MethodsA total of 169,891 patients in Peking Union Medical College Hospital (PUMCH) and 29,458 patients in Inner Mongolia People’s Hospital (IMPH) from January 2018 to December 2020 were included, and the results of ANA (antinuclear antibodies) and special antibodies were analyzed retrospectively.ResultsThe positive rates of ANA and RR patterns were 34.84%, 0.16% in PUMCH, and 44.73%, 0.23% in IMPH. Anti-RR antibodies mainly appear in adults (≥ 41 years), mostly of low or medium fluorescence titers. Isolated RR patterns were mostly presented (60.30% and 69.12%, respectively), and the RR pattern mixed with the speckled pattern was most commonly observed among patients having two or more patterns. The RR pattern existed in a variety of diseases including hepatitis C, AIDs, pulmonary diseases, nephropathy diseases, and even healthy people. The highest prevalence of the RR pattern was observed in hepatic diseases, such as hepatic dysfunction (0.79%), hepatic cirrhosis (1.05%), PBC (0.85%), and AIH (0.65%), etc. The positive rate of specific antibodies in RR pattern cases was 31.25%, and anti-Ro52 (27, 20.61%) was the most common target antibody.ConclusionThe RR pattern had a low prevalence in ANAs test samples and varied in different nationalities and regions. Except for hepatitis C, it could be observed in AIDs, pulmonary diseases, nephropathy, other hepatic diseases, and even healthy people, but the positive rate was slightly higher in hepatic diseases. Its mechanism of action and clinical relevance still need clarification.

OA24 Airway obstruction in an adolescent: relapsing polychondritis

OA24 Airway obstruction in an adolescent: relapsing polychondritis

Clinical features of different stage subacute combined degeneration of the spinal cord.

Subacute combined degeneration (SCD), caused by vitamin B12 disorders, leads to severe degeneration of the spinal cord. Thus, it is significant to make timely diagnosis and treatment options of SCD. The objectives were to summarize clinical features of different sate SCD. Clinical data of 42 SCD patients of spinal cord were retrospectively analyzed, which were classified into early stage, middle stage and late stage SCD. Among the patients, 9 were classified into early stage, 22 into middle stage, and 11 into late stage SCD. Total cholesterol and hemoglobin levels were relatively higher in late stage SCD. In contrast, mean corpusular volume (MCV) level was higher in early stage SCD. There were typical abnormalities only in 8 patients on magnetic resonance imaging (MRI), and a dynamia was a common neurological abnormality in all patients. Importantly, the differences in abnormal findings in anti-nuclear antibodies (ANA) testing, visual acuity and fundus testing were statistically significant in different stage SCD (P < .05). There were correlation between most variances with SCD stage. Strikingly, there existed close relationship between enhanced levels of blood glucose (r = −0.289, P = .066), glycated hemoglobin (GHB) (r = −0.288, P = .068) and homocysteine (r = −0.563, P = .000), abnormal visual findings (r = 0.309, P = .049) and megaloblastic anemia (r = −0.295, P = .061) with different SCD stage, among which abnormal visual findings were closely associated with middle stage SCD. Moreover, levels of total cholesterol, blood glucose, homocysteine and abnormal finding of visual acuity were significant in diagnosis and clinical staging of SCD (P < .05). Although MRI scanning and serum vitamin B12 level were widely used for SCD diagnosis, neurological examination and homocysteine level may be more potentially valuable indexes for SCD diagnosis and staging.

Complement activation products vs standard ANA testing: Treatment outcomes, diagnosis, and economic impact (CAPSTONE) in systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) is a complex clinical diagnosis historically aided by imperfect biomarkers. The advent of a multianalyte assay panel incorporating innovative cell-bound complement activation markers necessitates a comparison of its clinical utility to conventional autoantibodies for the diagnosis and treatment of SLE. OBJECTIVES: To compare the likelihood of SLE diagnosis, SLE treatment initiation, and the downstream impact on health care utilization among patients tested with AVISE Lupus (AVISE) vs standard-of-care laboratory testing with the traditional antinuclear antibody (ANA) testing strategy cohort (tANA). METHODS: An observational retrospective cohort study was conducted using electronic health record (EHR) data from the Illumination Health registry, which integrates EHR records from more than 300 rheumatologists across the US. Health records from January 2016 to December 2020 and administrative claims with cost data for a subset of patients linkable to the HealthCore Integrated Research Database and Medicare data were analyzed. The AVISE and tANA test results were classified as positive, negative, or indeterminate, and outcomes were stratified based on test results. Two cohorts were established: AVISE testing strategy and the tANA approach. Analyses included test impact on SLE diagnosis, treatment initiation, patterns of repeat testing, and downstream health care utilization. Multivariable logistic regression was used to estimate odds ratios (ORs) comparing the likelihood of SLE medication initiation and SLE diagnosis between the AVISE and tANA cohorts. RESULTS: The main cohort included 21,827 AVISE testing episodes and 22,778 tANA testing episodes. A total of 2,437 (11.2%) patients tested positive by AVISE compared with 5,364 (23.6%) of tANA positive patients. Among patients with no baseline prescription for SLE medication(s), patients with a positive AVISE test result were more likely to initiate SLE medications compared with tANA positive patients (43% vs 32%; OR = 1.57; 95% CI = 1.41-1.76). The treatment effect was larger in patients new to the practice within the preceding year (55% vs 33%; adjusted OR = 2.77; 95% CI = 2.31-3.32). AVISE positive patients were more than 5-fold more likely to be diagnosed with SLE, as compared with the tANA patients (31% vs 8%; OR = 5.11; 95% CI = 4.43-5.89), and similar in the new patient cohort (30% vs 6%; OR = 6.34; 95% CI = 5.12-7.86). Linked EHR-Medicare data revealed a greater decrease in posttest vs pretest mean annualized outpatient laboratory testing in AVISE negative (-$985; P < 0.0001) vs tANA negative (-$356; P < 0.0001) patients. A similar analysis in the EHR-HealthCore linked data revealed similar numerical trends as the Medicare data for outpatient laboratory testing but did not reach significance (P > 0.05). Cost comparisons in the categories of hospitalization, emergency department, outpatient imaging, and pharmacy costs did not yield significant differences. CONCLUSIONS: The significantly greater likelihood of SLE diagnosis and SLE medication initiation in AVISE positive vs tANA positive patients is consistent with improved clinical actionability, potentially shortening time to diagnosis. AVISE negative patients experienced a greater decrease in outpatient laboratory testing posttest relative to tANA negative patients, supporting the improved negative predictive value of AVISE vs tANA. DISCLOSURES: Mr O'Malley and Dr Zack are employed by Exagen Inc. Drs Curtis and Xie, Ms Su, and Ms Clinton are affiliated with the University of Alabama at Birmingham. Mr Haechung and Dr Grabner are employees of HealthCore, Inc., which received funding from Bendcare (owner of the Illumination Health Registry) for the conduct of parts of the study on which this manuscript is based. Exagen Inc. provided funding to Bendcare for the conduct of the study. Dr Grabner is also a shareholder of Anthem, Inc.

Detection of serum IgG autoantibodies to FcεRIα by ELISA in patients with chronic spontaneous urticaria.

Mast cells are a key effector cell in the pathogenesis of chronic spontaneous urticaria (CSU) and activated by circulating FcεRI-specific IgG as well as IgE. This study evaluated the prevalence of circulating autoantibodies to FcεRIα in the sera of CSU patients. Eighty-eight patients with CSU and 76 healthy controls (HCs) were enrolled. To detect circulating autoantibodies (IgG/IgA/IgM) to FcεRIα, ELISA was done using YH35324 (as a solid phase antigen), and its binding specificity was confirmed by the ELISA inhibition test. The antibody levels were presented by the ratio of YH35324-preincubated to mock-preincubated absorbance values. Clinical and autoimmune parameters, including atopy, urticaria activity score (UAS), serum total/free IgE levels, serum antinuclear antibody (ANA) and autologous serum skin test (ASST) results, were assessed. The autoimmune group was defined if CSU patients had positive results to ASST and/or ANA. The ratio of serum IgG to FcεRIα was significantly lower in CSU patients than in HCs (P<0.05), while no differences were noted in serum levels of IgG to recombinant FcεRIα or IgA/IgM autoantibodies. The autoimmune CSU group had significantly lower ratios of IgG/IgA (not IgM) autoantibodies to FcεRIα than the nonautoimmune CSU group (P<0.05 for each). No significant associations were found between sex, age, atopy, urticaria duration, UAS, or serum total/free IgE levels according to the presence of IgG/IgA/IgM antibodies. This study confirmed the presence of IgG to FcεRIα in the sera of CSU patients, especially those with the autoimmune phenotype.

The Anti-Cytoplasmic and Anti-Mitotic Autoantibodies; Are These Antibodies Associated with Diseases?

Examination of antinuclear antibody (ANA) is used in diagnosis of systemic autoimmune diseases, and the indirect immunofluorescence (IIF) assay using HEp-2 cells is the gold standard method. HEp-2 allows the detection of multiple target antigen-directed autoantibodies. The guide “The International Consensus on ANA Patterns (ICAP)”, characterizes the patterns into three groups: nuclear, cytoplasmic, and mitotic. The majority of these are associated with autoimmune diseases, but some are rarely seen in autoimmune diseases or may be associated with conditions other than autoimmune disease. There is no consensus on how to report cytoplasmic and mitotic patterns-negative or positive. We aimed to examine the characteristics of patients that had cytoplasmic or mitotic staining in ANA evaluation by IIF. In our Medical Microbiology Laboratory, 18985 ANA tests of 16940 patients were studied between 01.01.2015-31.12.2019. Cytoplasmic or mitotic pattern was detected in 393 (2.07%) tests belonging to 385 patients. Cytoplasmic patterns suggestive of anti-mitochondrial antibody (AMA), anti-smooth muscle antibody (ASMA), anti-Jo-1 and anti-ribosomal P-protein were not included. The most common patterns were anti-midbody, anti-spindle fibers, and anti-vimentin patterns. There were 66 rheumatology patients that were negative for ANA but had cytoplasmic or mitotic staining. There was no statistically significant difference between the diagnosis and patterns of these patients. We suggest that the ANA should be reported as “negative” in case of cytoplasmic or mitotic pattern unless the term anti-cell antibody is used. It should be noted in the description part of the report in order to distinguish significant cytoplasmic patterns and give an idea for some specific conditions.

Acrosyndromes vasculaires paroxystiques : démarche pratique de diagnostic et de prise en charge

Paroxysmal vascular acrosyndromes are related to a peripheral vasomotor disorder and presented as paroxysmal color changes of the fingers. They include primary Raynaud's phenomenon (RP), which is the most common, secondary RP and erythermalgia. They are to be distinguished from non-paroxysmal acrosyndromes such as acrocyanosis and chilblains, which are very frequent and often associated with RP, digital ischemia and necrosis, spontaneous digital hematoma and acrocholosis. The challenge of a consultation for a vascular acrosyndrome is to make positive diagnosis through history and clinical examination, and to specify its nature, to prescribe complementary exams. In any patient consulting for RP, assessment includes at least an antinuclear antibody test and capillaroscopy. For erythermalgia, a blood count and even a search for JAK2 mutation are required. A thryoid-stimulating hormon assay, a test for antinuclear antibodies, and a search for small fiber neuropathy are also performed. The treatment of RP is essentially documented for secondary RP where calcium channel blockers are indicated in first line, and iloprost in severe cases. The treatment of primitive erythermalgia is based on sodium channel blockers such as mexiletine or lidocaine infusions, and on drugs effective on neuropathic pain, such as gabapentin or amitryptiline, in case of erythermalgia associated with small fiber neuropathy. The treatment of erythermalgia associated with myeloproliferative syndromes is based on etiological treatment and aspirin.

Malar rash with pancytopenia

Malar rash with pancytopenia

P-766 Birth outcomes in Anti-centromere antibody (ACA) -positive patients treated with ART

Abstract Study question Does the presence of the ACA have any effect on pregnancy and birth? Summary answer Presence of ACA did not have an impact on pregnancy and birth parameters measured. What is known already We have previously shown that patients with high levels of anti-centromere antibody (ACA), one of the anti-nuclear antibodies (ANA), frequently have dispersion of chromosomes in the cytoplasm. Additionally, we reported that it was characterized by a low oocyte maturation rate as observed at ovum pick up, high multiple pronuclear formation after fertilization and a low pregnancy rate after embryo transfer. Thus, the effect of ACA on fertility is clear, but the impact following pregnancy establishment has not yet been reported. Therefore, we followed up on birth outcomes in ACA-positive patients treated with ART. Study design, size, duration 3379 patients who underwent ANA testing followed by embryo transfer between January 2014 and February 2020 and who gave birth including the results of single births with no abnormal or missing values for week and birth weight were analyzed. The subjects were classified into three groups: ANA-negative (without ACA or any other ANA), ACA-positive (with only ACA) and ANA-positive (with ANA but not ACA). Participants/materials, setting, methods We compared mean birth weight (full term), low weight birth infant (less than 2,500g) rate, sex ratio, congenital anomaly rate, preterm birth rate, cesarean section rate, and mean apgar score (AP) in the three groups. We treated “don't know” and “blank” for items other than week and birth weight as non-responses and missing values. Main results and the role of chance Of the 3379 cases for analysis, the group numbers were ANA-: 2465, ACA+: 21, ANA+: 893. The mean birth weights were 3099.6g, 3055.3g and 3088.5g respectively. In the 3 groups the rate of low birth weight infants were 8.7% (215/2465), 9.5% (2/21) and 9.2% (82/893), the sex ratio (male/female)-1.03 (1246/1212), 0.62 (8/13) and 0.93 (429/ 460), congenital anomaly rate 2.7% (67/2465), 4.8% (1/21), 3.2% (29/893), preterm birth rate 7.4% (86/2465), 4.8% (1/12), 6.7% (60/893), cesarean rate 40.0% (979/2448), 42.9% (9/21), 41.3% (367/888), and mean AP was 8.3, 8.2, and 8.3 respectively. There was no significant difference between the three groups in any of the measured items. Limitations, reasons for caution This study was conducted at a single institution, and only the results of those who responded to the birth survey questionnaire were analyzed. Because of the small number of patients in the ACA group, continued follow-up is considered necessary. Wider implications of the findings It was shown that ACA strongly affects maternal fertility, but seems to have no effect on birth parameters. However we will continue to follow up with further long-term prognostic studies. Trial registration number not applicable

P1646: PRIMARY IMMUNE THROMBOCYTOPENIA (ITP) IN PATIENTS OLDER THAN 75 YEARS: REAL WORLD DATA FROM THE ITP REGISTRY OF THE HELLENIC SOCIETY OF HEMATOLOGY

Background: ITP incidence is known to increase in adults aged >60 years and even more in men aged >75 years (Moulis G et al., Blood 2014; 124(22):3308). As population aging and life-expectancy continues to increase worldwide, ITP in the elderly is a growing concern in everyday clinical practice. There are only a few studies regarding the features of ITP in patients (pts) aged >60-65 years and data are even scarcer in pts aged ≥75 years Aims: To describe real world characteristics at diagnosis and evaluate disease outcome in a group of pts aged 60-74 years (Group-1) as compared to very old pts (≥75 years; Group-2) with primary ITP, using data from the national database (ITP registry) operated under the auspices of the Hellenic Society of Hematology Methods: The Greek ITP registry recruits pts (n=1560, to date) nationally through a network of 25 sites. In the present study we retrospectively analyzed data from pts with primary ITP aged ≥60 years, who were diagnosed from 1979 to 2021. Results: The total number of evaluable pts was 298. Group-1 consisted of 180 and Group-2 of 118 pts. The mean age at diagnosis was 68 years (60.1-74.9) in Group-1 and 81 years (75.2-97.1) in Group-2. The female to male ratio did not differ between the 2 groups. The median platelet count at diagnosis was significantly higher in Group-1 (20x109/L, interquartile range: 5-44x109/L) than in Group-2 (11x109/L, interquartile range: 5-32x109/L; P=0.0096). Comorbidity rates did not differ between Group-1 and Group-2, with the exception of hypertension and chronic kidney disease, which were less frequently reported in Group-1 (P=0.0092 and P=0.0179, respectively). Concurrently used medications as a whole and also vitamin-K antagonists were reported less frequently in Group-1 (P=0.03 and P=0.049, respectively). Bleeding manifestations at diagnosis were comparable across the two age-groups. The choice of diagnostic procedure did not differ between Goup-1 and Group-2, with the exception of anti phospholipid antibody and anti nuclear antibody testing which were performed more frequently in Group-1 (P=0.048 and P=0.0002, respectively). Similar rates of positive laboratory test results were reported in the two age-groups. Fewer pts received treatment at diagnosis in Group-1 (P=0.023). Overall response rate did not differ between the two Groups. A similar proportion of Group-1 and Group-2 patients were treated with corticosteroids, intravenous IgG or both, rituximab, anti-D, immunoglobulin or thrombopoietin receptor agonists. Splenectomy was performed in 2.8% of Group-1 pts but in none of Group-2 pts. At 1 year after diagnosis, a similar proportion of Group-1 and Group-2 pts had developed chronic ITP. Summary/Conclusion: Very elderly pts (Group-2) presented with lower platelet counts at diagnosis and required ITP treatment more frequently than elderly pts (Group-1). Furthermore, Group-2 pts suffered more often from hypertension and chronic kidney disease and used more often anticoagulant agents. On the other hand, the 2 age-groups did not differ in the frequency or the location of bleeding. Age did not seem to particularly influence the diagnostic workup or the choice of treatment, with the exception of splenectomy which was not performed in Group-2 patients. The outcome of the disease was comparable in the 2 age-groups, as suggested by the similar treatment response rates and chronic ITP frequencies. Further investigation is warranted to full characterize the very elderly pts with ITP and unravel the unmet need of this cohort in order to optimize management.

Purple-brown coalescing macules on the mandibular area of the face.

This patient presented with a 1-year history of violaceous-brown, coalescing reticulated macules on his face, with no similar lesions in other body areas. Laboratory findings were normal and antinuclear antibody test was negative. Histopathological findings included lichenoid tissue reaction and prominent pigmentary incontinence. Click here for the corresponding questions to this CME article.

An indirect comparison of automated indirect immunofluorescence vs automated solid-phase immunoassays for antinuclear antibody detection: A meta-analysis and adjusted indirect comparison of diagnostic test accuracy.

The primary aim of this study was to conduct a meta-analysis to compare the diagnostic accuracy of automated indirect immunofluorescence (automated-IIF) and fully automated solid-phase immunoassays (solid-phase assays), compared with gold standard conventional manual indirect immunofluorescence (manual-IIF) for antinuclear antibody (ANA) detection. Indirect meta-comparison was performed using prospective studies reporting comparative data between automated-IIF and fully automated solid-phase assays individually to conventional manual-IIF. Diagnostic tests regarding different automated solid-phase assays and automated-IIF for ANA detection were retrieved from the Cochrane Library, PubMed, Embase, Web of Science, Chinese Biological Medicine Database (CBM), China National Knowledge Infrastructure (CNKI), and WANFANG electronic databases from their inception to January 2022. Assessment of the quality of the studies was undertaken using a second version of the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. The investigated diagnostic indices including pooled sensitivity, pooled specificity, pooled positive likelihood ratio (PLR), pooled negative likelihood ratio (NLR), pooled diagnostic odds ratio (DOR), area under the summary receiver operating characteristic (AUC) of automated-IIF and solid-phase assays, respectively. Relative diagnostic odds ratio (RDOR) was calculated to indirectly compare the diagnostic accuracy of automated-IIF and solid-phase assays. To visualize results, we provide forest plots showing the RDOR with 95% confidence intervals (CI) of the 2 methods against the "gold standard" manual-IIF by R software. Deeks' funnel was used to investigate the publication bias. A total of 16 studies involving 6111 subjects were included in the analysis. The pooled sensitivity, pooled specificity, pooled PLR, pooled NLR, pooled DOR and the AUC were 0.85 (95% CI: 0.84-0.86), 0.82 (95% CI 0.81-0.84), 14.22 (95% CI 8.55-23.65), 0.06 (95% CI 0.03-0.12), 287.0 (95% CI 124.30-662.68) and 0.983 for automated-IIF respectively, and as for solid-phase assays those were 0.73 (95% CI 0.70-0.75), 0.87 (95% CI 0.85-0.89), 5.66 (95% CI 3.33-9.62), 0.30 (95% CI 0.20-0.47), 19.14 (95% CI 8.00-45.79) and 0.894. The results of indirect comparison indicated that automated-IIF had statistically significant higher accuracy for the detection of ANA. This meta-analysis and indirect comparison suggest that automated-IIF should be recommended as an alternative assay for ANA screening under the condition of increased demand for ANA testing in clinical immunology laboratories.

КЛИНИКО-ДИАГНОСТИЧЕСКОЕ ЗНАЧЕНИЕ АНТИНУКЛЕАРНЫХ АНТИТЕЛ В ПРАКТИКЕ ПЕДИАТРА (ЧАСТЬ I)

In recent decades, there has been an increase in the incidence of various autoimmune, including rheumatic diseases, while their debut has been shifted to an earlier age. The clinical picture of rheumatic diseases is distinguished by severe polymorphism; therefore, laboratory diagnostic methods are important for diagnostic search. One of the most widely used tests in the rheumatological practice is the detection and identification of antinuclear antibodies (ANA). ANA are a large group of autoantibodies (auto-Abs) directed against various cell structures, including not only the nucleus but also the nuclear membrane, mitotic apparatus, cytoplasm components and cell organelles, as well as cell membranes. Different methods are used for testing, but the method of ANA detection through indirect immunofluorescence antinuclear antibody test (IF-ANA) is recommended as a “gold standard” with human laryngeal carcinoma HEp-2 cells being recognized as a standard substrate. IF-ANA with HEp-2 has the highest diagnostic sensitivity compared with other methods, it includes the phase of serial dilutions of positive serums and a visual analysis of the type of glow, the list of which currently has 30 patterns. ANA glow types are caused by various auto-Abs that respond with antigens located in the nucleus and cytoplasm of the HEp-2 cells line. Assessment of the type of glow in conjunction with clinical and laboratory data allows planning of further examination with confirming tests to determine the specificity of ANA, some of which, in particular, are auto-Abs to DFS70 antigen, which in the absence of other types of autoantibodies, are more likely to doubt the presence of a systemic rheumatic disease. The diagnostic specificity of various screening techniques for ANA detection is relatively low, they are detected with a fairly high frequency in patients with other diseases and in healthy individuals of different gender and age, including children.

Finding the Role of Elevated Antinuclear Antibodies (ANA) in Diagnosis and Treatment of Medically Critically Ill Patients

Introduction: Antinuclear antibody (ANA) testing is an important screening tool for autoimmune conditions, such as systemic lupus erythematosus (SLE) and scleroderma. Objectives: Finding the role of elevated antinuclear antibodies (ANA) in diagnosis and treatment of medically critically ill patients. Material and methods: This cross sectional study was conducted THQ Hospital, Muree during July 2021 to November 2021. The data was collected from 600 patients of different diseases. In patient with multiple hospitalizations, the most recent one was considered for the study. Results: The data was collected from 600 patients had their ANA levels drawn, out of which 78 were positive and 522 were negative. Out of the ANA positive patients, 14 (17 percent) had the values to 1:40, 29 (35 percent) had values to 1:80, 14 (17 percent) had values to 1:160, 8 (9.7 percent) had values to 1: 320, 11 (13.2 percent) had values to 1:640, 4 (4.8 percent) had values to 1:1280, 2 (2.4 percent) had values greater than &gt;1:1280. Conclusion: It is concluded that in patients with RA, important differences exist between those who are ANA‐positive and ANA‐negative in terms of time to fulfillment of RA criteria and time to DMARD initiation as well as choice of initial pharmacotherapy. Keywords: ANA, Patients, Medically, Diagnosis

Prevalence and characteristics of inflammatory rheumatic diseases in patients with thalassemia.

Reports of inflammatory rheumatic diseases (IRD) in thalassemia are limited. This study aimed to determine the prevalence and clinical characteristics of IRD in patients with thalassemia disease. Consecutive adult patients with thalassemia disease, confirmed by hemoglobin typing, attending the Hematology Clinic between June 2019 and May 2021 were invited to join this study. All of them had their history taken and a physical examination for IRD. Those with IRD had their medical records reviewed. Sixty-three patients (transfusion-dependent in 50) were included in this study. There was α-, β-, and co-inheritance of α- and β-thalassemia in 22.22%, 73.02%, and 4.76% of the patients, respectively, with β-thalassemia/Hb E disease in 53.97%. Twenty-three patients had IRD (rheumatoid arthritis in 9, gout in 6, systemic lupus erythematosus in 3, spondyloarthropathy in 2, and one patient each with dermatomyositis, overlap syndrome, and unclassified polyarthralgia). Clinical manifestations and laboratory findings were similar to IRD patients in general. In 40 patients without IRD, direct and indirect Coombs tests and antinuclear antibody (ANA) were positive in 51.72%, 27.59%, and 10.26%, respectively. When comparing among these 40 patients, between those with non-transfusion-dependent thalassemia (n = 10) and those with transfusion-dependent thalassemia (n = 30), the latter had non-significantly more positive direct Coombs (60.87% vs. 16.67%), indirect Coombs (30.43% vs. 16.67%), and ANA tests (13.33% vs. 0%). The prevalence of IRD in patients with thalassemia disease was rather high. Positive direct Coombs test and ANA were common in transfusion-dependent patients.