Anti-cytokine autoantibodies are associated with opportunistic infection in patients with thymic neoplasia.
Patients with thymic malignancy have high rates of autoimmunity leading to a variety of autoimmune diseases, most commonly myasthenia gravis caused by anti-acetylcholine receptor autoantibodies. High rates of autoantibodies to cytokines have also been described, although prevalence, spectrum, and functionality of these anti-cytokine autoantibodies are poorly defined. To better understand the presence and function of anti-cytokine autoantibodies, we created a luciferase immunoprecipitation system panel to search for autoantibodies against 39 different cytokines and examined plasma from controls (n = 30) and patients with thymic neoplasia (n = 17). In this screen, our patients showed statistically elevated, but highly heterogeneous immunoreactivity against 16 of the 39 cytokines. Some patients showed autoantibodies to multiple cytokines. Functional testing proved that autoantibodies directed against interferon-α, interferon-β, interleukin-1α (IL-1α), IL-12p35, IL-12p40, and IL-17A had biologic blocking activity in vitro. All patients with opportunistic infection showed multiple anti-cytokine autoantibodies (range 3-11), suggesting that anti-cytokine autoantibodies may be important in the pathogenesis of opportunistic infections in patients with thymic malignancy. This study was registered at http://clinicaltrials.gov as NCT00001355.
Burbelo
Peter D
PD
Neurobiology and Pain Therapeutics, Laboratory of Sensory Biology, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
Browne
Sarah K
SK
Sampaio
Elizabeth P
EP
Giaccone
Giuseppe
G
Zaman
Rifat
R
Kristosturyan
Ervand
E
Rajan
Arun
A
Ding
Li
L
Ching
Kathryn H
KH
Berman
Arlene
A
Oliveira
Joao B
JB
Hsu
Amy P
AP
Klimavicz
Caitlin M
CM
Iadarola
Michael J
MJ
Holland
Steven M
SM
D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood*; D001324:Autoantigens / Q000276:immunology; D016207:Cytokines / Q000276:immunology*; D005260:Female; D006801:Humans; D007118:Immunoassay; D015151:Immunoblotting; D047468:Immunoprecipitation; D008297:Male; D008875:Middle Aged; D009894:Opportunistic Infections / Q000097:blood / Q000453:epidemiology / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013953:Thymus Neoplasms / Q000097:blood / Q000150:complications* / Q000276:immunology*; D055815:Young Adult
D001323:Autoantibodies; D001324:Autoantigens; D016207:Cytokines