Antinuclear antibodies (ANA) in chronic hepatitis C virus infection: correlates of positivity and clinical relevance.

We examined correlates of antinuclear antibody (ANA) positivity (ANA+) in individuals with chronic hepatitis C virus (HCV) infection and the effect of positivity on clinical outcome of HCV. Pretreatment sera from 645 patients from three centres in Sweden (n = 225), the UK (n = 207) and Italy (n = 213) were evaluated by indirect immunofluorescence on Hep-2 cells for ANA pattern and titre by a single laboratory. Liver biopsies were all scored by one pathologist. A total of 258 patients were subsequently treated with interferon monotherapy. There was a significant difference in the prevalence of ANA (1:40) by geographic location: Lund 4.4%, London 8.7%, Padova 10.3% [odds ratio (OR) = 0.66; 95% CI: 0.46-0.94; P = 0.023]. Duration of HCV infection, age at infection, current age, route of infection, viral genotype, alcohol consumption, fibrosis stage and inflammatory score were not correlated with ANA+ or ANA pattern. Female gender was correlated with ANA+ and this association persisted in multivariable analyses (OR = 3.0; P = 0.002). Increased plasma cells were observed in the liver biopsies of ANA-positive individuals compared with ANA-negative individuals, while a trend towards decreased lymphoid aggregates was observed [hazard ratio (HR) = 9.0, P = 0.037; HR = 0.291, P = 0.118, respectively]. No correlations were observed between ANA positivity and nonresponse to therapy (OR = 1.4; P = 0.513), although ANA+ was correlated with faster rates of liver fibrosis, this was not statistically significant (OR = 1.8; P = 0.1452). Low titre ANA+ should not be a contraindication for interferon treatment. Our observation of increased plasma cells in ANA+ biopsies might suggest B-cell polyclonal activity with a secondary clinical manifestation of increased serum immunoglobulins

Applying Choosing Wisely: Antinuclear Antibody (ANA) and Sub-Serology Testing in a Safety Net Hospital System.

ObjectiveIn 2013, the American College of Rheumatology (ACR) participated in the Choosing Wisely campaign and devised a recommendation to avoid testing antinuclear antibody (ANA) subserologies without a positive ANA and clinical suspicion of disease. The goals of our study were to describe ANA and subserology ordering practices and predictors of ordering concurrent ANA and subserologies in a safety-net hospital.MethodsWe identified ANA and subserologies (dsDNA, Sm, RNP, SSA, SSB, Scl-70 and centromere) completed at Denver Health between 1/1/2005 and 12/31/2011. Variables included demographics, primary insurance, service, and setting from which the test was ordered. We performed multivariable logistic regression to determine predictors of concurrent ordering of ANA and subserologies.ResultsDuring seven years, 3221 ANA were performed in 2771 individuals and 211 (6.6%) were performed concurrently with at least one subserology. The most common concurrent subserologies were dsDNA (21.8%), SSA (20.8%), and SSB (19.7%). In the multivariable logistic analysis, significant predictors of concurrent ANA and subserologies were the labs being ordered from subspecialty care (OR 8.12, 95% CI 5.27-12.50, p-value <0.0001) or from urgent/inpatient care (OR 3.86, 95% CI 1.78-8.38, p-value 0.001). A significant predictor of decreased odds was male gender (OR 0.32, 95% CI 0.21-0.49, p-value <0.0001). Five individuals (2.2% of the negative ANA with subserologies ordered) had a negative ANA but positive subserologies.ConclusionOf 3221 ANA, 6.6% were performed concurrently with subserologies, and subspecialists were more likely to order concurrent tests. A negative ANA predicted negative subserologies with rare exceptions, which validates the ACR's recommendations

The importance of detecting anti-DFS70 in routine clinical practice : comparison of different care settings

Background: Screening for antinuclear antibodies by indirect immunofluorescence (ANA-IIF) is essential in the diagnostic workup of ANA-associated autoimmune rheumatic diseases (AARDs). However, also healthy individuals may test positive, making the interpretation challenging. Recent reports suggest that dense fine speckled 70 antibodies (anti-DFS70) may facilitate this challenge. Here, we investigate their clinical importance based on data from four Belgian laboratories (one primary, two secondary and one tertiary care). Methods: At least one specific DFS70 assay (DFS70 IgG ELISA or lineblot [Euroimmun, full length antigen] and/or DFS70 IgG CLIA [Inova Diagnostics, truncated antigen]) was performed on four consecutive cohorts of homogeneous-like ANA-IIF samples (n = 697). Co-occurrence with AARD-specific ANA and clinical information were documented in the anti-DFS70-positive samples. Results: Using a combination of solid phase techniques, we found between 7.6% and 26% anti-DFS70 in the different cohorts. Focusing on anti-DFS70 CLIA-positive samples without co-occurrence of AARD-specific ANA, we observed a trend towards lower frequency in tertiary (8% [p = 0.0786]) and secondary care (12% [p = 0.1275] and 6% [p < 0.001]) compared to primary care (21%). Moreover, in this specific subpopulation, AARD was less frequent (0%-50% compared to 6%-77% in the total anti-DFS70-positive group). Conclusions: Anti-DFS70 prevalence depends on the applied assay and care setting. Our data suggest that, for an ANA-IIF-positive patient, it is rather the absence of AARD-associated ANA and clinical symptoms that contribute to the exclusion of AARD than the presence of anti-DFS70. Nevertheless, isolated anti-DFS70 helps to clarify positive ANA-IIF results, especially if pretest probability for AARD is low

Do we need broad immunological work-up in all patients with CIS?

BACKGROUND: The aim of this study was to determine the prevalence of altered immunological tests and their clinical significance in patients with clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS). ----- PATIENTS AND METHODS: The information was gathered from medical records of patients hospitalized in the Referral Center for Demyelinating Diseases in the 2008-2010 period. All patients had ANA, ENA profile, ANCA, aCl IgG and IgM, C3, C4, CH50, anti-TPO, AST and RF antibodies tested. ----- RESULTS: From 726 patients with CIS that were reviewed, the complete battery of immunological tests was performed in 418 of them (57.6%), representing our cohort. Altered tests were found in 235 patients (56.2%); 73 (17.4%) had positive antinuclear antibodies, 14 (3.3%) had positive ENA, 47 (11.2%) had positive aCl IgG, 83 (19.8%) had positive aCl IgM, and 13 (3.1%) had anti TPO antibodies. We found no correlation between ANA, aCl IgG or IgM positivity (ANA vs aCL IgG p=0.554; ANA vs aCL IgM p=0.19; aCL IgG vs aCL IgM, p=0.155). None of the patients had any clinical manifestations other than MS symptoms. ----- CONCLUSION: These results indicate that significant number of patients with CIS have altered immunological tests but nevertheless none of them had clinical expression of any other autoimmune disease making them clinically insignificant. In conclusion there is no need to perform extensive immunological work-up in all patients with CIS. Contrary, our results argue for more focused testing rather than a battery of screening tests

Nonlocal Harnack inequalities

We state and prove a general Harnack inequality for minimizers of nonlocal, possibly degenerate, integro-differential operators, whose model is the fractional p-Laplacian.Comment: To appear in J. Funct. Ana

THE INVESTIGATION OFANTI NUCLEAR ANTI BODY (ANA) IN VISCERAL LEISHMANIASIS IN ARDABIL IN 1384-1385

Introduction: The ANA test is a blood test that is commonly used for evaluating of autoimmune or connective tissue disorders.The ANA test identifies auto antibodies that target the nucleus of cells. The ANA test in women and elderly people, certain medications and chronic infectious diseases may be positive. Visceral leishmaniasis is a chronic infectious diseases wich the cellular Immune mechanisms responsible for the control of leishmania infections.This study attempted to investigate the ANA in leishmaniasis, since there was a probability of observing highly positive ANA in this disease. Materials & Methods: In this study, we collected samples of blood of children who were infected by visceral leishmaniasis and the DAT of samples were reported positive (titer1/800 & higher) through contacting with central laboratory of hygience center. Then we sent these frozen serums to laboratory to study ANA through ELISA methods. The number of samples was 26 and was collected from three hygienic centers in Ardebil, Meshkin and Germi within 1.5 years. In one sample the DAT of serum was negative, but in the biopsy of bone marrow the leishman's body was reported. The participants were 9 (34.6%) females and 17 (65.4%) males and their ages varied from 5 months to 5 years (mean 21 months). Results assessed by using descriptive and analytic statistics tests. Results: In the 11 cases (42.3%) the ANA test was positive and in 15 cases (57.7%) was negative. P=0/000(P0.05 that wasn't significant. Conclusion: our study indicates that visceral leishmaniasis is a infectious disease witch in the antinuclear antibody(ANA) test can be positive. Presense of positive ANA test in visceral leishmaniasis probably be due to disease pathogenesis and changes in immune system and it's disorders. So false positive anti nuclear antibody (ANA) test in visceral leishmaniasis can be seen

Autoimmune thyroiditis in antinuclear antibody positive children without rheumatologic disease

<p>Abstract</p> <p>Background</p> <p>Children are commonly referred to a pediatric rheumatology center for the laboratory finding of an Anti-nuclear antibody (ANA) of undetermined significance. Previous studies regarding adult rheumatology patients have supported an association between ANA and anti-thyroid antibodies, with the prevalence of thyroid antibodies being significantly higher in patients referred to a rheumatology center for an ANA without evidence of connective tissue disease compared to the general population. The purpose of the present study was to determine the frequency of thyroid antibodies in children referred to a pediatric rheumatology center for a positive ANA without evidence of a connective tissue disease.</p> <p>Methods</p> <p>A retrospective chart review was performed on children who were referred to our pediatric rheumatology center between August 2003 and March 2007 for positive ANA with concurrent thyroid antibody and thyroid function tests performed who did not fulfill criteria for a specific connective tissue disease. Laboratory and clinical features were recorded and analyzed. Mean and standard deviation were used to describe continuous data. Chi-square or Fisher's exact tests were used to compare proportions between variables.</p> <p>Results</p> <p>One-hundred and four ANA-positive patients with concurrent thyroid studies were evaluated (88% female, 93% Caucasian, mean age 11.9 ± 4.0 years). Half of patients had an ANA titer ≥ 1:320. The ANA pattern was speckled in 60% of the patients. Thyroid antibodies were detected in 30% of the patients. Anti-Thyroglobulin (ATG) was detected in 29% and Anti-thyroid peroxidase (ATPO) in 21% of the patients; of these children, 14% had hypothyroidism. ANA pattern and titer were not associated with anti-thyroid antibody positivity.</p> <p>Conclusion</p> <p>Thyroid antibodies associated with chronic lymphocytic thyroiditis, ATG and ATPO, were detected significantly higher in ANA-positive children without a rheumatologic condition (30%) as compared to the general pediatric population (1.3 - 3.4%). ANA titer and pattern did not help predict the presence or absence of thyroid antibodies. Given the high frequency of thyroid antibodies and increased risk of developing hypothyroidism over time, routine evaluation of ATG and ATPO with thyroid function tests in ANA-positive children is recommended.</p

Cytokine-associated neutrophil extracellular traps and antinuclear antibodies in Plasmodium falciparum infected children under six years of age

<p>Abstract</p> <p>Background</p> <p>In <it>Plasmodium falciparum</it>-infected children, the relationships between blood cell histopathology, blood plasma components, development of immunocompetence and disease severity remain poorly understood. Blood from Nigerian children with uncomplicated malaria was analysed to gain insight into these relationships. This investigation presents evidence for circulating neutrophil extracellular traps (NETs) and antinuclear IgG antibodies (ANA). The presence of NETs and ANA to double-stranded DNA along with the cytokine profiles found suggests autoimmune mechanisms that could produce pathogenesis in children, but immunoprotection in adults.</p> <p>Methods</p> <p>Peripheral blood smear slides and blood samples obtained from 21 Nigerian children under six years of age, presenting with uncomplicated malaria before and seven days after initiation of sulphadoxine-pyrimethamine (SP) treatment were analysed. The slides were stained with Giemsa and with DAPI. Levels of the pro-inflammatory cytokines IFN-γ, IL-2, TNF, CRP, and IL-6, select anti-inflammatory cytokines TGF-β and IL-10, and ANA were determined by immunoassay.</p> <p>Results</p> <p>The children exhibited circulating NETs with adherent parasites and erythrocytes, elevated ANA levels, a Th2 dominated cytokine profile, and left-shifted leukocyte differential counts. Nonspecific ANA levels were significant in 86% of the children pretreatment and in 100% of the children seven days after SP treatment, but in only 33% of age-matched control samples collected during the season of low parasite transmission. Levels of ANA specific for dsDNA were significant in 81% of the children both pre-treatment and post treatment.</p> <p>Conclusion</p> <p>The results of this investigation suggest that NET formation and ANA to dsDNA may induce pathology in falciparum-infected children, but activate a protective mechanism against falciparum malaria in adults. The significance of in vivo circulating chromatin in NETs and dsDNA ANA as a causative factor in the hyporesponsiveness of CpG oligonucleotide-based malaria vaccines is discussed.</p