No abstract

Autoantibodies directed to chromatin components date back to the discovery of the LE cell and the LE cell phenomenon circa 1950, and subsequent evidence that major components of that reaction were chromatin components and histones in particular. Over time, immunoassays ranging from ELISA and line immunoassays to more modern bead-based assays incorporated histone and DNA mixtures, purified histones, and purified nucleosomes leading to a more thorough understanding of the genesis and pathogenetic relationships of antibodies to chromatin components in systemic lupus erythematosus and other autoimmune conditions. More recently, interest has focussed on other components of chromatin such as high mobility group (HMG) proteins both as targets of B cell responses and pro-inflammatory mediators. This review will focus on immunoassays that utilize chromatin components, their clinical relationships, and newer evidence implicating HMG proteins and DNA neutrophil extracellular traps (NETs) as important players in systemic autoimmune rheumatic diseases.

The study was registered at http://www.clintrials.gov . NCT02645565.

Objective To examine the clinical correlates and survival in patients with anti-fibrillarin antibodies (AFA) in a large international study population consisting of well-characterized systemic sclerosis (SSc) cohorts from Canada, Australia, and the United States of America. Methods Baseline clinical data from the prospective cohorts [Canadian Scleroderma Research Group (CSRG), the Australian Scleroderma Cohort Study (ASCS) and the American Genetics versus Environment in Scleroderma Outcome Study (GENISOS)] were investigated. Clinical variables were harmonized and sera were tested for AFA using a commercially available systemic sclerosis profile line immunoassay (LIA), regardless of the immunofluorescence staining pattern. Association of demographic and clinical features with AFA was investigated by logistic or linear regression. Furthermore, a survival analysis was performed by Cox regression analysis. Results A total of 1506 SSc patients with complete serological profiles were included in the study. Fifty-two (3.5%) patients had antibodies detected against fibrillarin. Patients of African descent and Native North American ethnicity were more likely to be AFA positive compared to other ethnicities. After adjustment for demographic factors, diffuse involvement and intestinal bacterial overgrowth requiring antibiotics, gastrointestinal reflux disease showed a trend for association with AFA. Furthermore, AFA positivity was associated with shorter survival independently of demographic factors and disease type (HR 1.76, 95% CI 1.11, 2.79, p=0.016). Conclusion In this large multinational SSc cohort, AFA was associated with Native American Ethnicity and was an independent predictor of mortality.

Risk of type 1 diabetes at 3 years is high for initially multiple and single Ab+ IT and multiple Ab+ NT. Genetic predisposition, age, and male sex are significant risk factors for development of Ab+ in twins.