Anticytokine Autoantibody Profiling in Five Types of Systemic Vasculitis

Sarthak Gupta^1,2, Seema K. Patel², Mary Blake², Massimo G. Gadina², Wanxia L. Tsai², Simon Carette³, David Cuthbertson⁴, Gary S. Hoffman⁵, Nader A. Khalidi⁶, Curry L. Koening⁷, Carol A. Langford⁵, Carol A. McAlear⁸, Larry W. Moreland⁹, Paul A. Monach¹⁰, Christian Pagnoux³, Philip Seo¹¹, Ulrich Specks¹², Antoine G. Sreih¹³, Steven R. Ytterberg¹⁴, Sarah K. Browne^1,15, Steven M. Holland¹, Mariana J. Kaplan², Peter A. Merkel¹⁶, Peter C. Grayson² and Vasculitis Clinical Research Consortium, ¹Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, ²National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, ³Division of Rheumatology, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada, ⁴Biostatistics and Informatics, Department of Pediatrics, University of South Florida, Tampa, FL, ⁵Rheumatology, Cleveland Clinic, Cleveland, OH, ⁶Division of Rheumatology, St. Joseph’s Health Care, McMaster University, Hamilton, ON, Canada, ⁷Division of Rheumatology, University of Utah, Salt Lake City, UT, ⁸Division of Rheumatology, University of Pennsylvania, Philadelphia, PA, ⁹Rheumatology & Clinical Immunology, University of Pittsburgh, Pittsburgh, PA, ¹⁰Rheumatology, Boston University School of Medicine, Boston, MA, ¹¹Division of Rheumatology, Johns Hopkins University, Baltimore, MD, ¹²Division of Pulmonary and Critical Care Medicine, Mayo Clinic College of Medicine, Rochester, MN, ¹³Department of Rheumatology, University of Pennsylvania, Philadelphia, PA, ¹⁴Rheumatology Division, Mayo Clinic, Rochester, MN, ¹⁵Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, ¹⁶Penn Vasculitis Center, Division of Rheumatology, University of Pennsylvania, Philadelphia, PA

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: autoantibodies, large vessel vasculitis, polyarteritis nodosa and vasculitis, Wegener's granulomatosis

Session Information

Date: Sunday, November 8, 2015

Title: Vasculitis Poster I

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose:

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.

Methods:

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.

Results:

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.

Conclusion:

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.

Disclosure: S. Gupta, None; S. K. Patel, None; M. Blake, None; M. G. Gadina, None; W. L. Tsai, None; S. Carette, None; D. Cuthbertson, None; G. S. Hoffman, None; N. A. Khalidi, None; C. L. Koening, None; C. A. Langford, None; C. A. McAlear, None; L. W. Moreland, None; P. A. Monach, None; C. Pagnoux, None; P. Seo, None; U. Specks, None; A. G. Sreih, None; S. R. Ytterberg, None; S. K. Browne, None; S. M. Holland, None; M. J. Kaplan, None; P. A. Merkel, None; P. C. Grayson, None.

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 .

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