Anti-cytokine autoantibodies are associated with opportunistic infection in patients with thymic neoplasia

作者:Burbelo Peter D; Browne Sarah K*; Sampaio Elizabeth P; Giaccone Giuseppe; Zaman Rifat; Kristosturyan Ervand; Rajan Arun; Ding Li; Ching Kathryn H; Berman Arlene; Oliveira Joao B; Hsu Amy P; Klimavicz Caitlin M; Iadarola Michael J; Holland Steven M
来源:Blood, 2010, 116(23): 4848-4858.
DOI:10.1182/blood-2010-05-286161

摘要

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-alpha, interferon-beta, interleukin-1 alpha (IL-1 alpha), 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. (Blood. 2010;116(23):4848-4858)

  • 出版日期2010-12-2
  • 单位NIH