Risk factors for ANA positivity in healthy persons

Abstract

IntroductionThe finding of antinuclear antibody (ANA) positivity in a healthy individual is usually of unknown significance and in most cases is benign. However, a subset of such individuals is at risk for development of autoimmune disease. We examined demographic and immunological features that are associated with ANA positivity in clinically healthy persons to develop insights into when this marker carries risk of progression to lupus.MethodsBiological samples from healthy individuals and patients with systemic lupus erythematosus (SLE) were obtained from the Dallas Regional Autoimmune Disease Registry (DRADR). Measurements carried out on serum samples included ANA, extractable nuclear antibodies (ENA) and autoantibody profiling using an array with more than 100 specificities. Whole blood RNA samples from a subset of individuals were used to analyze gene expression on the Illumina platform. Data were analyzed for associations of high ANA levels with demographic features, the presence of other autoantibodies and with gene expression profiles.ResultsOverall, ANA levels are significantly higher in females than in males and this association holds in patients with the autoimmune diseases lupus and rheumatoid arthritis (RA) as well as in healthy controls (HC). Age was not significantly associated with ANA levels and the elevated ANA values could not be explained by higher IgG levels. Another autoantibody, anti- cyclic citrullinated peptide (CCP), did not show gender dimorphism in rheumatoid arthritis (RA) or healthy individuals. The autoantigen array showed significant elevations of other autoantibodies in high ANA HCs. Some of these autoantibodies were directed to antigens in skin and others were related to autoimmune conditions of kidney, thyroid or joints. Gene expression analyses showed a greater prevalence of significantly upregulated genes in HCs with negative ANA values than in those with significant ANA positivity. Genes upregulated in high ANA HCs included a celiac disease autoantigen and some components of the Type I interferon (IFN) gene signature.ConclusionsRisks for ANA positivity include female gender and organ-specific autoimmunity. Upregulation of skin-specific autoantibodies may indicate that early events in the break of tolerance take place in cutaneous structures. Some of these changes may be mediated by Type I IFN. Blood profiling for expressed autoantibodies and genes has the potential to identify individuals at risk for development of autoimmune diseases including lupus.

Evaluation of Anti-Nuclear antibody test results in clinical practice

“…16 Most of the ANA positive people don't developed an autoimmune disease and this is consisted with low prevalence of rheumatologic disorders (5-7%) despite the rate of ANA presence. 9 ANA positivity can be detected 20-30% at 1/40, 10% at 1/80 and 5% at 1/160 dilution in healthy people. 17 Li et al suggest that the persistence of the positive ANA may be a part of the component of the normal immune response.…”

“…7 ANA positivity rate found in our female patients (77%) is consistent results with the knowledge of the autoimmune diseases are more frequent in women. 8,9 This predominance was researched by Leo and et al According to their study, the hormone profile, fetal microchimerism and some strategic genes which are on the sex chromosomes are playing role on this relationship. 10 As expected, the most of the positive ANA results were from rheumatology department (50%) in our study.…”

“…17 Li et al suggest that the persistence of the positive ANA may be a part of the component of the normal immune response. 9 In the study of Mariz et al, ANA positive healthy people were followed up for four years of period and none of them developed any symptoms. Along the period, 72.5% of the ANA positivity persisted on the same level, while 27.5% of them dropped below 1/80 and were reported as negative.…”

A Rabbit Model of Systemic Lupus Erythematosus, Useful for Studies of Neuropsychiatric SLE

“…The model developed using selectively bred pedigreed rabbits remains a promising one for further genetic investigations. As is found in human sera (Li et al, 2011), some rabbits had detectable pre-immune antinuclear antibodies (ANA) by ELISA. ANA of sixteen of twenty-four rabbits in group 5, including four immunized with only MAP-8 backbone had an increased ELISA value (delta OD) above pre-immune of 1.0 or more optical density units after the third boost.…”

“…Protein arrays containing microbial and autoantigens have been used to extend information on patients' serum profiles beyond the standard tests used in diagnosis (see for example, Robinson et al, 2002;Quintana et al, 2004;Li et al, 2005;Fattal et al 2010). Recently, Li et al, (2011) used protein microarrays to determine risk factors for ANA positivity in healthy persons and concluded that serum profiles of autoantibodies can potentially identify healthy individuals with potential to develop lupus and other autoimmune diseases. Their observations extended the widely quoted earlier observations by Arbuckle et al, (2003) that autoantibodies develop as much as ten years before the clinical onset of SLE.…”