Antinuclear antibody profiling in uveitis.

Abstract

Antinuclear antibodies (ANA) are antibodies directed against a variety of nuclear antigens and are detected in patients with autoimmune diseases. Antinuclear antibodies (ANA) profiling is relevant for diagnostic purposes in various diseases, including systemic lupus erythematosus (SLE), Sjögren syndrome and systemic sclerosis (Smeenk et al. 1990; Hamaguchi 2010). In the past, ANA were also determined in all patients with uveitis for diagnostic screening purposes; however, this approach has been abandoned as its relevance in adult patients with uveitis was shown to be limited (Murray 1986). In the last decades, analysis of ANA has greatly improved and various subtypes and staining patterns are currently appreciated. Therefore, this study aimed to assess the presence, subtypes and titres of ANA in adult patients with uveitis of different aetiologies and re-evaluate its possible value for diagnostic screening in uveitis. We conducted a prospective study at the Erasmus MC, University Medical Center Rotterdam and determined ANA profile (presence, titre, staining pattern and ANA subtype) in 105 consecutive adult patients with uveitis who underwent a standardized screening protocol for the cause of their uveitis between January 2016 and July 2017. In addition, all patients underwent a diagnostic screening protocol, which was related to the location of uveitis [according to the Standardization of Uveitis Nomenclature (SUN) Working Group]. A tailored approach was applied for further examinations. Clinical data from included patients were collected from medical charts. The study was performed in accordance with the Declaration of Helsinki and in agreement with the institutional regulations and approval of our institutional review board. Screening for ANA was performed by standard indirect immunofluorescence on HEp2 cells. Antinuclear antibodies (ANA) titres of 1:80 or higher were considered positive, and in these samples, ANA pattern and ANA titre were determined. Additionally, identification of anti-extractable nuclear antigens (ENA: SS-A, SS-B, U1RNP, Sm, CenpB, Scl-70, and Jo-1) and anti-double-stranded DNA (dsDNA) was performed by EliA (Thermo Fisher Scientific/Phadia, Freiburg, Germany), ELISA (Inova, San Diego, CA) and/or LIA (Euroimmun, Lübeck, Germany). Fisher's exact test for categorical data, and Mann–Whitney U-test, Kruskal–Wallis 1-way ANOVA test and Spearman's Rank Correlation for continues variables were performed to evaluate the presence and characteristics of ANA in uveitis patients. Positive ANA results were observed in 29 of 105 (28%) of patients with uveitis (Table 1) with a median titre of 160 (range: 80–640). Most ANA-positive samples were observed in idiopathic uveitis (18 of 55, 33%), and no positive ANA were seen in patients with uveitis classified as a clinical ocular syndrome (e.g. birdshot chorioretinopathy). Positive ANA titres were associated with increased duration of uveitis (p = 0.037). All other clinical characteristics of uveitis were not significantly associated with the presence or titre of ANA (all p-values > 0.05). The ANA pattern was classified as nuclear in 27 of 29 (93%) of patients and as mitotic in the remaining 2 of 29 (7%) patients. A speckled ANA pattern was the most frequent observed pattern (15 of 29, 52%), followed by a homogeneous pattern (9 of 29, 31%). Anti-extractable nuclear antigens (anti-ENA) and dsDNA were detected in a minority (1 of 29 (2%) and 2 of 29 (7%), respectively). The distribution of ANA pattern, anti-ENA and -dsDNA was not characteristic for specific causes, locations or clinical manifestations of uveitis. The prevalence of 28% ANA positivity in uveitis patients is higher than the prevalence of 8–13% in age-matched healthy population (Tan et al. 1997; Fernandez et al. 2003). However, the ANA profile was not distinctive for specific causes or clinical manifestations of uveitis. Therefore, routine ANA determination as a part of the diagnostic work-up of uveitis patients is not recommended. Determining ANA should however be performed in cases with signs suggesting specific systemic diseases such as SLE or children with uveitis associated with juvenile idiopathic arthritis.