Antinuclear Antibody-positive Patients Research Articles

Distribution characteristics of antinuclear antibodies in Guillain-Barré syndrome and its relationship with disease severity

BackgroundGuillain-Barré syndrome (GBS), an acquired immune-mediated autoimmune disorder affecting the peripheral nervous system (PNS), is associated with autoimmunity. The presence of autoantibodies in the blood is an important feature of autoimmune diseases. Herein, we explored the distribution characteristics of the antinuclear antibodies (ANAs) in GBS and the correlation between ANAs and disease severity. Materials and methodsWe retrospectively analyzed the clinical data of 170 GBS patients. According to ANAs, GBS patients were divided into ANAs positive and negative groups. The clinical characteristics of these two groups were compared. The distribution difference was also compared between male and female GBS patients. In addition, all enrolled patients were divided into more severe group and milder group according to whether the Hughes score at nadir ≥ 3 or not. Gender, age, and ANAs were compared between the two groups. ResultsIn this study, the positive rate of ANAs was 27.1 % in 170 GBS patients, among which anti-SSA-52/Ro52 antibody and antimitochondrial antibody M2 made up the largest proportion. In the ANAs positive group, GBS patients had longer days of hospitalization, more respiratory function involvement, and higher level of CSF IgG than the ANAs negative group. Compared to the ANAs negative group, Medical Research Council (MRC) scores on admission and at nadir were lower, and Hughes functional Grading Scale (HFGS) scores on admission and at nadir were higher in GBS patients with ANAs positive group. Erasmus GBS Respiratory Insufficiency Score (EGRIS) in ANAs positive GBS patients group was significantly higher than ANAs negative group. Gender had no effects on the distribution of ANAs in GBS patients. Moreover, we found that the anti-SSA-60 antibodies and age were positively correlated with GBS severity. In addition, in the anti-SSA-60 antibody positive group, GBS patients had longer days of hospitalization, more respiratory function involvement, higher HFGS scores on admission/at nadir, and lower MRC scores at nadir compared with the anti-SSA-60 antibody negative group. ConclusionAnti-SSA-52/Ro52 antibody and antimitochondrial antibody M2 were the most common ANAs in GBS patients. Anti-SSA-60 antibodies and age positively correlated with GBS severity. Positive anti-SSA-60 antibodies and age were independent predictors of GBS patient severity.

ABO and Rh blood group distribution in ANA positive patients

Aims: Antinuclear antibody (ANA) positivity is a common finding in various autoimmune diseases, particularly those of rheumatologic origin. While ANA positivity alone may not be diagnostic, it serves as a valuable marker when supported by clinical findings, aiding in the diagnosis and prediction of autoimmune diseases. The relationship between blood group systems and various diseases has been an area of interest in medical research. In this study, we aimed to investigate the potential association between ABO blood group and ANA positivity, specifically examining whether the ABO blood group status poses a risk for autoimmune diseases in individuals with rheumatologic conditions. Methods: In this retrospective study, we analyzed the blood group data of 536 patients who tested positive for ANA and were receiving treatment for rheumatologic diseases. The blood group status of these individuals was determined using standard serologic techniques. The distribution of ABO and Rh factor blood groups among ANA-positive patients was compared with the blood group distribution in the general population. Statistical analysis was performed to assess any significant differences. Results: The analysis revealed that the distribution of ABO and Rh factor blood groups among ANA-positive individuals did not show a statistically significant difference compared to the general population. Specifically, there was no significant deviation in the prevalence of ABO blood groups (A, B, AB, O) or Rh factor (positive or negative) among ANA-positive patients compared to expected frequencies based on population data. Conclusion: Based on our findings, there appears to be no significant association between ABO blood group status and ANA positivity in patients with rheumatologic diseases. The distribution of ABO and Rh blood groups among ANA-positive individuals closely resembled that of the general population. Therefore, our study suggests that current blood group status may not serve as a predictive factor for autoimmune diseases in individuals who test positive for ANA. Further research is warranted to explore other potential factors contributing to autoimmune disease susceptibility.

Machine learning approaches to identify systemic lupus erythematosus in anti-nuclear antibody-positive patients using genomic data and electronic health records

BackgroundAlthough the 2019 EULAR/ACR classification criteria for systemic lupus erythematosus (SLE) has required at least a positive anti-nuclear antibody (ANA) titer (≥ 1:80), it remains challenging for clinicians to identify patients with SLE. This study aimed to develop a machine learning (ML) approach to assist in the detection of SLE patients using genomic data and electronic health records.MethodsParticipants with a positive ANA (≥ 1:80) were enrolled from the Taiwan Precision Medicine Initiative cohort. The Taiwan Biobank version 2 array was used to detect single nucleotide polymorphism (SNP) data. Six ML models, Logistic Regression, Random Forest (RF), Support Vector Machine, Light Gradient Boosting Machine, Gradient Tree Boosting, and Extreme Gradient Boosting (XGB), were used to identify SLE patients. The importance of the clinical and genetic features was determined by Shapley Additive Explanation (SHAP) values. A logistic regression model was applied to identify genetic variations associated with SLE in the subset of patients with an ANA equal to or exceeding 1:640.ResultsA total of 946 SLE and 1,892 non-SLE controls were included in this analysis. Among the six ML models, RF and XGB demonstrated superior performance in the differentiation of SLE from non-SLE. The leading features in the SHAP diagram were anti-double strand DNA antibodies, ANA titers, AC4 ANA pattern, polygenic risk scores, complement levels, and SNPs. Additionally, in the subgroup with a high ANA titer (≥ 1:640), six SNPs positively associated with SLE and five SNPs negatively correlated with SLE were discovered.ConclusionsML approaches offer the potential to assist in diagnosing SLE and uncovering novel SNPs in a group of patients with autoimmunity.

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.

Do Antinuclear Antibodies Influence the Clinical Features of Chronic Spontaneous Urticaria?: A Retrospective Cohort Study.

Antinuclear antibody (ANA) is often used as a screening test for autoimmune comorbidities in patients with chronic spontaneous urticaria (CSU). However, the relationship of ANA status and the clinical course of the disease have not been fully described. To compare clinical features of CSU patients who are positive and negative for ANA. This was a retrospective cohort study that enrolled CSU patients attending the Urticaria Clinic at Siriraj Hospital from 2013 to 2019. Demographics, clinical characteristics, laboratory investigations, and treatments were collected until July 2021. All patients were investigated for ANA. Clinical feature data was compared between CSU patients with positive ANA and negative ANA groups using the 2-sample t-test and the Mann-Whitney U test for quantitative variables. The chi-squared test or Fisher's exact test was conducted to explore the association of qualitative variables. Disease relapse and remission were analysed via Kaplan-Meier survival analysis. Of 323 CSU patients, 31% had positive ANA. There were no significant differences in disease severity or impairment in quality of life. Patients with a positive ANA test had significantly lower prevalence of allergic rhinitis (p = .048) and significantly higher level of erythrocyte sedimentation rate (p = 0.007). Kaplan-Meier survival analysis showed that 2% of ANA positive CSU patients achieved remission status after one year and 28% did so after five years. There was no statistically significant difference in time to remission and time to relapse between ANA-positive and negative groups. Positive ANA in CSU patients could not indicate the differences in main disease characteristics from the ANA-negative CSU patients. Investigation for ANA may be useful in CSU patients who are suspected of having autoimmune diseases.

The clinical characteristics of nuclear dense fine speckled pattern in 95 289 patients

To investigate the distribution and clinical significance of nuclear dense fine speckled (DFS) pattern in various diseases. A total of 95 289 patients who received DFS tests at Peking Union Medical College Hospital from January 2019 to December 2020 were included in this study. The results of indirect immunofluorescence assay (IIF) for detection of antinuclear antibody (ANA) were evaluated. The positive rates of ANA and DFS were 39.60% (37 733/95 289) and 1.19% (1 139/95 289) respectively. The positive rate of DFS in ANA-positive patients was 3.02% (1 139/37 733). DFS and ANA positivity were significantly different among different age groups rather than gender. The positivity rate of DFS reached the peak (55.57%, 633/1 139) in young patients between 21-40 years, while positive ANA with negative DFS was mainly observed in patients between 41-60 years (37.26%, 13 636/36 594). Additionally, single ANA-positivity were mainly detected in rheumatology department (59.23%, 18 402/31 066), whereas positive DFS was more common in obstetrics and gynecology department (3.08%, 49/1 593). There were 82.88% (944/1 139) patients with positive DFS diagnosed with non-autoimmune disease (non-AID), and 19.49%(222/1 139) with dermatosis. Positive DFS with higher titer (≥1∶320) was detected more frequently in autoimmune disease (AID) patients (5.13%, 10/195) than in non-AID patients (1.69%, 16/944) (P<0.05). The DFS pattern is rare in ANA positive patients, which is mainly observed in women between 21-49 years. High titer of DFS is prevalent in AID patients, but positive DFS is detected more in non-AID patients, especially those with dermatosis.

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

P282 ANA seroconversion during prior anti-TNF therapy abolishes anti-CCP antibody positivity as a predictor of abatacept retention in rheumatoid arthritis

Abstract Background/Aims Few long-term drug survival analyses have been reported for patients with rheumatoid arthritis (RA) treated with abatacept. Here we report a machine learning approach to investigate drug-survival of abatacept over 5 years in RA patients. Methods We performed a retrospective observational study on a tertiary hospital dataset of RA patients who started abatacept between January 2008 and December 2020. Time to abatacept discontinuation over 5 years was estimated using Kaplan-Meier survival analyses. A multivariate cox-proportional hazard model to predict abatacept discontinuation was chosen by random survival forest and partial least regression. Results A total of 112 RA patients (81% female, mean age 58.1 [SD 13.5] years) received abatacept. Mean disease duration was 18.3 months (SD 13.6). More than half (65/112) were co-prescribed at least one conventional synthetic DMARD (csDMARD). Methotrexate was the most frequently concomitant csDMARD (n = 37), followed by hydroxychloroquine (n = 23), sulfasalazine (n = 15), and leflunomide (n = 7). 42 (37.5%) patients were treated with glucocorticoids (intermittent or continuous) with abatacept. Abatacept was mostly used as 4th (n = 29) and 3rd line (n = 24) bDMARD, but 19 patients received abatacept as their first line bDMARD. 75 (67%) patients were rheumatoid factor (RF) positive and 73 (65.2%) were anti-citrullinated protein antibody (ACPA) positive. Anti-nuclear antibody (ANA) was positive (≥1:80) in 25 patients (pre-biologics) and 18 seroconverted to previously exposed anti-TNF (ANA seroconversion group). Abatacept was discontinued in 54 patients (48.2%); 19 (35.2%) due to an adverse event and 35 (64.8%) due to loss of efficacy. Overall, the median time to discontinuation of abatacept was 3.8 years. Multivariate cox-proportional hazard model revealed that ACPA positivity was associated with reduced risk of abatacept discontinuation with HR of 0.56 (95% CI 0.32-0.95,p=0.03) compared to the ACPA-negative group. In contrast, the ANA seroconversion group demonstrated worse retention of abatacept with HR of 2.67 (95% CI 1.39-5.16, p = 0.0033) compared to ANA-negative patients. Kaplan-Meier analysis demonstrated that in the ANA seroconversion group, retention of abatacept was significantly inferior to pre-anti-TNF ANA positive patients (p = 0.0084) and ANA-negative patients (p = 0.0041). ACPA positivity was associated with better survival only in the non-ANA seroconverted group with HR of 0.54 (95% CI 0.29-0.92, p = 0.041), after adjusted by propensity score. Combining abatacept with any csDMARDs reduced the risk of abatacept discontinuation with HR of 0.57 (95% CI 0.33-0.98, p = 0.043) after adjusting by propensity score. No statistical difference was found between first-line, second-line, or any subsequent chronology of use of abatacept. Conclusion Our data suggest that previous ANA seroconversion occurring whilst on anti-TNF therapy reduces subsequent abatacept retention and cancels out the protective effect of anti-CCP positivity. The mechanism through which this occurs is unclear and further prospective and mechanistic studies are needed to validate these findings. Disclosure J. Kimpton: None. M. Shipa: Grants/research support; MS is funded by Versus Arthritis. S. Yeoh: Grants/research support; SY is funded by the Royal College of Physicians, Rosetrees Trust, NIHR University College London Hospitals Biomedical Research Centre, UCLH Charities, and Versus Arthritis. E. Hawkins: None. M. Ehrenstein: Grants/research support; ME is supported (in part) by the University College London Hospital Biomedical Research Centre.

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

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

Clinical utility of anti-DFS70 for identifying antinuclear antibody-positive patients without systemic autoimmune rheumatic disease

The antinuclear antibody (ANA) test is a screening test for systemic autoimmune rheumatic disease (SARD). We hypothesised that the presence of anti-DFS70 in ANA-positive samples was associated with a false-positive ANA test and negatively associated with SARD. A retrospective analysis of patient samples received for ANA testing from 1 January 2016 to 30 June 2016 was performed. Patient samples underwent ANA testing via indirect immunofluorescence method and anti-DFS70 testing using enzyme-linked immunosorbent assay. Among a total of 645 ANA-positive samples, the majority (41.7%) were positive at a titre of 1:80. The commonest nuclear staining pattern (65.5%) was speckled. Only 9.5% of ANA-positive patients were diagnosed with SARD. Anti-DFS70 was found to be present in 10.0% of ANA-positive patients. The majority (51/59, 86.4%) of patients did not have SARD. Seven patients had positive ANA titre > 1:640, the presence of anti-double stranded DNA and/or anti-Ro60. The presence of anti-DFS70 in ANA-positive patients was not associated with the absence of SARD (Fisher's exact test, p = 0.245). The presence of anti-DFS70 was associated with a false-positive ANA test in 8.6% of our patients. Anti-DFS70 was not associated with the absence of SARD.

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.

Combined treatment of prednisone and hydroxychloroquine may improve outcomes of frozen embryo transfer in antinuclear antibody-positive patients undergoing IVF/ICSI treatment.

The influence of anti-nuclear antibody (ANA) on induced ovulation was controversial, and the effect of prednisone plus hydroxychloroquine (HCQ) treatment on frozen embryo transfer outcomes of in-vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) for ANA-positive women was unclear. Fifty ANA-positive women and one-hundred ANA-negative women matched for age and anti-Mullerian hormone (AMH) were included from a Reproductive Medical Central of a University Hospital. Sixty-one oocytes pick-up (OPU) cycles in ANA+ group and one-hundred OPU cycles in ANA- group were compared; 30 frozen embryo transfer cycles without treatment and 66 with prednisone plus HCQ treatment among ANA-positive women were compared. There was no statistical difference in number of retrieved oocytes (13.66 ± 7.71 vs 13.72 ± 7.23, p = .445), available embryos (5.23 ± 3.37 vs 5.47 ± 3.26, p = .347), high-quality embryos (3.64 ± 3.25 vs 3.70 ± 3.52, p = .832), and proportion of high-quality embryos (26.5% vs. 26.7%, p = .940). Biochemical pregnancy rate (33.3% vs. 68.2%, p < .05), clinical pregnancy rate (20.0% vs. 50.1%, p < .05), and implantation rate (5.6% vs. 31.8%, p < .05) were lower, and pregnancy loss rate (83.3% vs. 23.1%, p < .05) was higher in patients with treatment than no treatment. The influence of ANA on number of retrieved oocytes, available embryos, high-quality embryos, and proration of high-quality embryos was not found. The treatment of prednisone plus HCQ may improve implantation rate, biochemical pregnancy rate, and clinical pregnancy rate, and reduce pregnancy loss rate in frozen embryo transfer outcomes for ANA-positive women.

Antinuclear antibody patterns by indirect immunofluorescence test: An experience from a rural tertiary health centre of Puducherry, South India

Anti-nuclear antibodies (ANA) are known to be associated with autoimmune diseases and most commonly with connective tissue diseases (CTD). Screening for ANA is the first investigation of choice in the diagnosis of autoimmune diseases and indirect immunofluorescence (IIF) test using Hep-2 cells has been considered the gold standard method. The prevalence of autoimmune diseases and hence the ANA positivity and ANA IIF patterns differ in various geographical regions. This study was aimed to estimate the ANA positivity rates among patients with suspected or confirmed auto immune diseases and to determine the common ANA IIF patterns in the positive samples.: This is a retrospective study including 235 patients with either clinical suspicion of, or suffering from autoimmune diseases attending a tertiary health care hospital in Puducherry, South India, between November 2018 and April 2020. ANA IIF test (Hep 20-10/ primate liver, Euroimmun, Germany) was performed with 1:100 dilutions of patient serum.The ANA positivity rate was 14.5% (34 out of 235 samples were positive). ANA was positive in 10 (13.3%) males and 24 (15%) females. The mean age of ANA positive patients were 43.4 years.The most common pattern was nucleus fine granular (n=8) followed by cytoplasm fine granular (n=7) and centromere (n=4).A significant ANA positivity rate was found in our study and a detailed clinical study has to be conducted to draw further conclusions.

Clinical efficacy of high-dose dexamethasone with sequential prednisone maintenance therapy for newly diagnosed adult immune thrombocytopenia in a real-world setting.

ObjectiveAs first-line treatments for newly diagnosed adult immune thrombocytopenia (ITP), high-dose dexamethasone (HD-DXM) and conventional-dose prednisone achieve good initial responses, but their long-term efficacy is poor. To improve the long-term outcome of newly diagnosed ITP, we explored the efficacy and safety of HD-DXM with sequential prednisone maintenance therapy.MethodsThis retrospective study in a real-world setting assessed 72 consecutive newly diagnosed ITP patients administered first-line HD-DXM with sequential prednisone maintenance therapy from 1 June 2016 to 31 December 2019.ResultsSeventy patients obtained response (97.2%), and 55 achieved sustained response (SR) (76.4%). Fifty-three obtained complete remission (CR) (73.6%), and 39 achieved continuous CR at 6 months (54.2%). Among 36 anti-nuclear antibody-positive patients, 100% achieved response, and 28 achieved CR (77.8%). Among 24 antithyroid antibody-positive patients, 23 (95.8%) achieved response, and 20 achieved CR (83.3%). For patients with initial response, the 12-month probability of SR was 78.6%. For patients with initial CR, the 12-month probability of continuous CR was 64.2%. At 12 months, 21.4% of patients with initial response and 11.3% of patients with initial CR showed loss of treatment response.ConclusionsHD-DXM with sequential prednisone as the first-line treatment for newly diagnosed ITP patients may achieve good clinical efficacy.

Characterization of anti-nuclear antibodies in patients with oral submucous fibrosis and its clinicopathologic implications - An immunofluorescence study.

Background:Oral submucous fibrosis (OSF), widespread in the Indian subcontinent, is a chronic debilitating disease of the oral cavity having a high potential for malignancy. The etiology of OSF is debatable. However, recently, autoimmunity had been suggested to play a significant role in its etiology, yet unproven. Hence, this study was conducted to explore the presence of antinuclear antibodies (ANAs) in the serum of OSF patients which is one of the serum markers of autoimmune diseases and its possible clinicopathologic associations.Materials and Methods:A total of 105 blood samples were collected from patients with OSF (n = 45), age- and sex-matched healthy controls with (n = 30) and without (n = 30) areca nut chewing habit. Serum positivity of ANA was determined by immunofluorescence and correlated with the oral habits and severity of the disease measured by maximum mouth opening (MMO) and site of involvement.Results:Significantly higher incidence of ANA (35.6%) was found in 45 OSF patients than in the healthy group (P = 0.001). Prevalence of ANA positivity was found higher in females (n = 11; 68%) than males (P < 0.001). A significantly lower MMO (P = 0.00) was found in ANA positive patients (17 ± 6.21 mm) in contrast to MMO in ANA-negative patients (28.74 ± 6.58 mm). The mean duration of habit and frequency of habit between ANA positive and negative patients was not significant. A significantly more number of sites of involvement was seen in ANA positive cases (P = 0.004). Out of 16 ANA positive OSF cases, 10 cases showed + 2 and 6 cases showed + 3 fluorescence intensity. Speckled (n = 8), homogeneous (n = 5) and nucleolar pattern (n = 3) were the fluorescence patterns observed.Conclusion:The presence of autoantibodies such as ANA, female predilection, alteration of humoral and cellular immunity justifies OSF as an autoimmune disease. This study provides broader prospective to adopt therapies that selectively target autoimmune pathways.

Quantitative determination of agglutination based on the automatic hematology analyzer and the clinical significance of the erythrocyte-specific antibody

ObjectiveThe objective of this work was to explore the similarities and differences between the automatic hematology analyzer method and the traditional slide method in the detection of red blood cell (RBC) agglutination, and demonstrate that the automatic hematology analyzer is more intuitive and reliable for the detection of RBC agglutination. A further objective was to establish a new method to facilitate new ideas for clinical research. MethodsType A serum was selected and diluted 1:2, 1:4, 1:8, 1:16, and 1:32, to react with the type B cells and the normal saline group was used as the control group. An RBC count was performed using an automatic hematology analyzer, after incubation in a warm bath for 30 min. The degree of agglutination on the glass slide was also recorded. A positive serum of antinuclear antibody (ANA) was collected and RBC agglutination between RBC-O and ANA positive serum was determined using the automatic hematology analyzer method. ResultThe relationship between the results from the automatic hematology analyzer and the agglutination strength using the glass slide method was determined. There was a significant difference between the serum of ANA positive patients and the normal control group (P < 0.05). ConclusionA new method for detecting RBC agglutination using an automatic hematology analyzer has been established and is a valid tool for clinical research.

P316 Hepatobiliary manifestations measured by vibration-controlled transient elastography in inflammatory bowel disease: A prospective hospital-based cohort study

Abstract Background Intestinal mucosal injury is supposed to cause liver disease and inflammatory bowel disease (IBD), Crohn’s disease (CD) and ulcerative colitis (UC) is a typical chronic injury of intestinal mucosa. Therefore, we investigated the hepatobiliary manifestation with liver ultrasonography (LUS) and vibration-controlled transient elastography (VCTE) in IBD. Methods IBD patients newly diagnosed in Kosin University Gospel Hospital were enrolled consecutively. Gross hepatobiliary abnormality was evaluated with LUS and simultaneous liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) were assessed to evaluate hepatic injury and steatosis with VCTE. Laboratory tests including hepatic biochemistries, anti-nuclear antibody (ANA), and faecal calprotectin level (FC) were taken. Results Eighty-two (37 patients of CD and 45 UC) patients were enrolled. Gallbladder abnormality was noted in 39 patients (47.5%) including stone in 7, sludge in 11, polyp in 10, wall thickening in 9 and collapsed in 2. CAP &amp;gt;233 dB/m was in 33 patients (40.2%) and LSM &amp;gt;5.5 kPa in 10 (12.2%). Nineteen patients (23.2%) were diagnosed fatty liver. FC was 382 ± 785 (mean ± SD). CAP &amp;gt;233 dB/m was significantly associated with lower FC (209.6 vs. 352.1, p = 0.038). The correlation coefficient was −0.316 between CAP and FC (p = 0.006). LSM &amp;gt;5.5 kPa tended to be lower FC but was not statistically significant (199.8 vs. 306.2, p = 0.283). ANA was positive in 14 patients (17.1%). In ANA positive patients, FC was significantly higher than ANA negative patients (609.5 vs. 319.4, p = 0.015). Conclusion In this prospective analysis, the major hepatobiliary manifestations in IBD patients were gallbladder abnormality and fatty liver and there could be an association between low hepatic fat amount and intestinal disease activity.

N-acetylcysteine exposure is associated with improved survival in anti-nuclear antibody seropositive patients with usual interstitial pneumonia

BackgroundMortality is similarly high among individuals with usual interstitial pneumonia (UIP) due to idiopathic pulmonary fibrosis (IPF) and interstitial pneumonia with autoimmune features (IPAF). Circulating anti-nuclear antibodies (ANA) are commonly found in this patient population, suggesting possible aberrant immune activation. Because an environment of oxidative stress can result from immunologic activation, we hypothesized that ANA positive patients with UIP would have improved outcome when exposed to the antioxidant N-acetylcysteine (NAC) compared to ANA negative patients.MethodsA single center, retrospective cohort analysis was performed. Patients with UIP due to IPF and IPAF were stratified according to ANA status to and NAC exposure. Transplant-free survival (TFS) was assessed using the Kaplan-Meier estimator and multivariable Cox regression adjusted for diagnosis, gender/age/physiology score, immunosuppressant exposure and anti-fibrotic exposure.ResultsOf 293 individuals with UIP due to IPF (74%) or IPAF (26%), NAC exposure was documented in 58 (19.8%). Among NAC exposed individuals, 33 (56.9%) were ANA seropositive and 25 (43.1%) were seronegative. NAC exposure was associated with improved TFS survival among ANA seropositive individuals in unadjusted analysis (plogrank = 0.02) and after multi-variable adjustment (HR 0.51, 95% CI 0.30–0.87; p = 0.01). There was no association between NAC exposure and TFS in ANA seronegative individuals (HR 1.26, 95% CI 0.69–2.32; p = 0.45). Formal interaction testing confirmed NAC*ANA interaction (p = 0.04) and sensitivity analysis demonstrated an increasing effect size associated with NAC therapy as ANA titer increased. Among patients with available genetic data, a marginally higher proportion of ANA positive patients (p = 0.08) carried the rs3750920 (TOLLIP) genotype previously shown to predict favorable outcome in NAC exposed patients.ConclusionNAC exposure is associated with improved transplant-free survival ANA positive patients with UIP. These findings support the prospective collection of ANA data in in future NAC clinical trials performed in patients with UIP.

Antinuclear antibodies in scrub typhus: Transient occurrence during acute illness.

The pathological hallmark of scrub typhus infection is focal or disseminated vasculitis. As with other infections, antinuclear antibodies (ANA) have been previously described in scrub typhus. However, the underlying mechanisms and implications of this immunological phenomenon is not well understood. In the present work it was assessed whether ANA is associated with illness severity and outcomes. In this prospective study spanning one year, patients fulfilling the diagnostic criteria for scrub typhus were recruited. Patients with other acute infective febrile illnesses were taken as controls. ANA positivity was compared between the cases and controls. ANA in scrub typhus was assessed for correlation with disease severity, organ dysfunction and outcomes. The cohort comprised of 149 patients (scrub 89; controls 60) with mean age 46.5 (SD=16.9) yr; 48.3% were female. ANA was detected in 48 (53.9%) patients with scrub typhus and 9(15%) controls (p < 0.001). The ANA pattern was predominantly speckled (93.8%) in both scrub typhus patients and controls. In patients with scrub typhus, ANA positivity was associated with increasing APACHE-III score [Odds ratio (OR) 1.01; 95% CI 0.99-1.03; p = 0.09]. On bivariate analysis, ANA tended to be correlated with acute respiratory distress syndrome (OR 2.32; 95% CI 0.98-5.46; p = 0.06), hepatic dysfunction (OR 2.25; 95% CI 0.94-5.39, p = 0.06) and aseptic meningitis (OR 6.83; 95% CI 0.80-58.05, p = 0.08). The presence of these antibodies did not correlate with duration of hospitalization or mortality. Convalescent sera on 31 ANA positive scrub typhus patients demonstrated persistence of ANA in only 5 (16.1%) patients. The disappearance of ANA during the convalescent phase suggests that ANA is expressed during the acute phase of scrub typhus infection. Its association with organ dysfunction warrants further study of the mechanisms and impact of autoantibody formation in scrub typhus.

Correlation of serum aquaporin 4 antibodies and condition and visual prognosis in patients with severe neuromyelitis optica spectral disorders

Objective To observe the correlation of serum aquaporin 4 (AQP4) antibodies and condition and visual prognosis in patients with severe neuromyelitis optica spectral disorders (NMOSD). Methods Fifty NMOSD patients with visual acuity of 20/200 or worse in at least one eye were enrolled in this retrospective analysis. There were 12 males and 38 females. The age ranged from 17 to 65 years, with the mean of (39.86±2.02) years. The patients were divided into two groups according to the serum AQP4-IgG status. The ophthalmologic examination, serum anti-nuclear antibodies (ANA), myelin oligodendrocyte glycoprotein (MOG) antibody detection and vision prognosis were compared and analyzed. Glucocorticoid therapy was delivered to 46 patients who were within 1 month of onset. The visual acuity of the patients after treatment was divided into complete recovery, partial recovery, stabilization and reduction, and the visual acuity of the two groups were analyzed. Results Among 50 patients, there were 30 (60%) seropositive patients (positive group), 20 (40%) seronegative patients (negative group). The positive group had significantly higher ratio of female to male (P=0.004), and more binocular optic neuritis (ON) (P=0.010) compared with the negative group. More recurrence ON were also found in the positive group, but without statistic difference between two groups (P=0.167). There was no difference of age, course, and vision damage degrees and abnormal orbital MRI scanning between two groups (P>0.05). Among 24 patients who underwent serum ANA detection in the positive group, 8 patients were positive. All of 18 patients who underwent serum ANA detection in the negative group were negative. The difference of the ratio of serum ANA positive patients between two groups was significant (P=0.030). Serum MOG antibody detection in the positive group was negative (0/10). Sixteen patients who underwent MOG antibody detection in negative group, 4 patients were positive. After treatment, there were 23.3%, 23.3%, 53.3% patients with vision of complete recovery, partial recovery and reduction in the positive group; 25.0%, 30.0%, 25.0% patients with vision of complete recovery, partial recovery and reduction in the negative group, respectively. There was no difference in proportion of vision with complete recovery and partial recovery between two groups (P=0.163, 0.607), but significant difference was observed in proportion of vision with stabilization and reduction between two groups (P=0.021, 0.048). Conclusions The positive serum AQP4 antibody is common in patients with severe NMOSD. The patients with AQP4 antibody in the serum are more likely combined with immunological serological markers and poor vision prognosis. Key words: Neuromyelitis optica; Visually impaired persons; Aquaporin 4