Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
Anticytokine autoantibodies (ACAs) are pathogenic in many
hematologic, pulmonary and infectious diseases. Evaluation in autoimmune
diseases, including systemic
lupus erythematosus (SLE), shows that ACAs are biologically active and may
contribute to disease pathogenesis. The
prevalence of ACAs and their correlation to
circulating cytokine levels in vasculitis
has not been characterized and was the focus of this study.
Patients with various forms of vasculitis were selected from a
multicentered, observational cohort and fulfilled modified ACR classification criteria for the respective
diseases. All patients had active disease at the time of sample collection and
had not received cyclophosphamide or rituximab within 6 months prior to sample
collection. Plasma samples from patients with 5
types of vasculitis (n=149) and healthy controls (n=25) were tested for autoantibodies
against 34 cytokines using a multiplex bead-based assay. For each ACA concentrations
above two standard deviations of the mean of healthy controls and more than
1000 fluorescence intensity were classified as positive. Cytokine measurements
were done using Human 25-Plex Panel (Invitrogen, Inc). Data were acquired on a Bio-Plex 100 instrument. Spearman’s
correlation coefficients were calculated to detect potential associations
between levels of cytokines and the relevant ACA.
The majority of patients (57%) had at least one ACA; however, the
prevalence of individual ACA ranged from 0 to 33% (Table 1). Autoantibodies
against TNF and LTa were seen in the setting of anti-TNF
monoclonal therapy. Compared to other types of vasculitis, an increased
prevalence of autoantibodies against Th2
cytokines (IL-4, 5, 10, 13, up to 17%) were seen in Takayasu’s arteritis and
autoantibodies against G-CSF (15%) and IL-2 (23%) were detected in
granulomatosis with polyangiitis (GPA). No autoantibodies against IL-6 were
seen. Significant correlations were identified in 2 of 18 relevant pairings between
ACAs and corresponding cytokine levels. IL-12 levels correlated weakly with anti-IL-12
autoantibodies (r=0.21, p<0.01), and soluble IL-2R levels, but not IL-2,
negatively correlated with anti-IL-2 autoantibodies
(r=0.23, p<0.01). Plasma IL-2R levels were significantly higher in
patients with GPA compared to the other types of vasculitis (668.3 vs 288.8
ng/ml, p<0.01); among patients with GPA IL-2R levels were 2-fold lower in
patients with anti-IL-2 autoantibodies.
ACAs occur at differing frequencies across the spectrum of vasculitis.
Interestingly, autoantibodies directed against IL-2 were observed
in a subset of patients with GPA and were negatively correlated with plasma IL-2R
levels, suggesting that these autoantibodies may
play a functional role in disease pathogenesis. Functional
studies of candidate ACAs in vasculitis are warranted.
To cite this abstract in AMA style:Gupta S, Patel SK, Blake M, Gadina MG, Tsai WL, Carette S, Cuthbertson D, Hoffman GS, Khalidi NA, Koening CL, Langford CA, McAlear CA, Moreland LW, Monach PA, Pagnoux C, Seo P, Specks U, Sreih AG, Ytterberg SR, Browne SK, Holland SM, Kaplan MJ, Merkel PA, Grayson PC. Anticytokine Autoantibody Profiling in Five Types of Systemic Vasculitis [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/anticytokine-autoantibody-profiling-in-five-types-of-systemic-vasculitis/. Accessed August 14, 2020.
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