The presence of anti-nuclear antibodies alone is associated with changes in B cell activation and T follicular helper cells similar to those in systemic autoimmune rheumatic disease

Abstract

BackgroundDiagnosis of systemic autoimmune rheumatic diseases (SARD) relies on the presence of hallmark anti-nuclear antibodies (ANA), many of which can be detected years before clinical manifestations. However, ANAs are also seen in healthy individuals, most of whom will not develop SARD. Here, we examined a unique cohort of asymptomatic ANA+ individuals to determine whether they share any of the cellular immunologic features seen in SARD.MethodsHealthy ANA− controls and ANA+ (ANA ≥1:160 by immunofluorescence) participants with no SARD criteria, with at least one criterion (undifferentiated connective tissue disease (UCTD)), or meeting SARD classification criteria were recruited. Peripheral blood cellular immunological changes were assessed by flow cytometry and transcript levels of BAFF, interferon (IFN)-induced and plasma cell-expressed genes were quantified by NanoString.ResultsA number of the immunologic abnormalities seen in SARD, including changes in peripheral B (switched memory) and T (iNKT, T regulatory, activated memory T follicular helper) subsets and B cell activation, were also seen in asymptomatic ANA+ subjects and those with UCTD. The extent of these immunologic changes correlated with ANA titer or the number of different specific ANAs produced. Principal component analysis of the cellular data indicated that a significant proportion of asymptomatic ANA+ subjects and subjects with UCTD clustered with patients with early SARD, rather than ANA− healthy controls.ConclusionsANA production is associated with altered T and B cell activation even in asymptomatic individuals. Some of the currently accepted cellular features of SARD may be associated with ANA production rather than the immunologic events that cause symptoms in SARD.Electronic supplementary materialThe online version of this article (10.1186/s13075-018-1752-3) contains supplementary material, which is available to authorized users.

Fatigue severity in anti-nuclear antibody-positive individuals does not correlate with pro-inflammatory cytokine levels or predict imminent progression to symptomatic disease

“…We and others have previously shown that elevated levels of type I IFN are associated with symptomatic progression in ANS and UCTD [52, 53]. Here, we show that there is no association between type I IFN levels and fatigue and that fatigue does not predict symptomatic progression.…”

Patient ancestry significantly contributes to molecular heterogeneity of systemic lupus erythematosus

“…Previous work has suggested a strong association between the IGS and autoantibodies ( 22 ) and the association of dsDNA autoantibodies with increased plasma cells ( 61 ) and Tregs ( 62 ) by flow cytometry. Our findings demonstrate that it is not the IGS that is ancestry dependent per se, as previously reported ( 26 ), but the presence of autoantibodies to RNP/Sm and the increased combination of autoantibodies that is associated with ancestry.…”

The baseline interferon signature predicts disease severity over the subsequent 5 years in systemic lupus erythematosus

“…For measurement of interferon (IFN)-induced gene expression, total RNA was isolated from the whole peripheral blood archived in PAXgene tubes (Applied Biosystems) and gene expression was quantified by NanoString using a custom array (nanoString Technologies), as previously described [20]. Log 2 normalized expression levels of 5 IFN-induced ubiquitously expressed genes (EPSTI1, IFI44L, LY6E, OAS3, RSAD2) were then summed to generate a composite IFN5 score [21].…”