1. Prevalence and pathogenicity of autoantibodies in patients with idiopathic CD4 lymphopenia
- Author
-
Perez-Diez, Ainhoa, Wong, Chun-Shu, Liu, Xiangdong, Mystakelis, Harry, Song, Jian, Lu, Yong, Sheikh, Virginia, Bourgeois, Jeffrey S., Lisco, Andrea, Laidlaw, Elizabeth, Cudrici, Cornelia, Zhu, Chengsong, Li, Quan-Zhen, Freeman, Alexandra F., Williamson, Peter R., Anderson, Megan, Roby, Gregg, Tsang, John S., Siegel, Richard, and Sereti, Irini
- Subjects
Thermo Fisher Scientific Inc. ,Skin diseases -- Development and progression ,B cells -- Health aspects ,Lymphocytopenia -- Development and progression ,Autoimmunity -- Health aspects ,Autoantibodies -- Health aspects ,Infection -- Development and progression ,Scientific equipment industry -- Health aspects ,T cells -- Health aspects ,Health care industry - Abstract
BACKGROUND. Idiopathic CD4 lymphopenia (ICL) is defined by persistently low [CD4.sup.+] cell counts ( METHODS. We hybridized 34 and 51 ICL patients' sera to a 9,000-human-proteome array and to a 128-known-autoantigen array, respectively. Using a flow-based method, we characterized the presence of anti-lymphocyte Abs in the whole cohort of 72 patients, as well as the Ab functional capability of inducing Ab-dependent cell-mediated cytotoxicity (ADCC), complement deposition, and complement-dependent cytotoxicity (CDC). We tested ex vivo the activation of the classical complement pathway on ICL [CD4.sup.+] T cells. RESULTS. All ICL patients had a multitude of autoantibodies mostly directed against private (not shared) targets and unrelated quantitatively or qualitatively to the patients' autoimmune disease status. The targets included lymphocyte intracellular and membrane antigens, confirmed by the detection by flow of IgM and IgG (mostly [IgG.sub.1] and [IgG.sub.4]) anti-[CD4.sup.+] cell Abs in 50% of the patients, with half of these cases triggering lysis of [CD4.sup.+] T cells. We also detected in vivo classical complement activation on [CD4.sup.+] T cells in 14% of the whole cohort. CONCLUSION. Our data demonstrate that a high prevalence of autoantibodies in ICL, some of which are specific for [CD4.sup.+] T cells, may contribute to pathogenesis, and may represent a potentially novel therapeutic target. TRIAL REGISTRATION. ClinicalTrials.gov NCT00867269. FUNDING. NIAID and National Institute of Arthritis and Musculoskeletal and Skin Diseases of the NIH., Introduction Idiopathic CD4 lymphopenia (ICL) was initially described in the late 1980s when some patients presented with opportunistic infections and CD4 lymphopenia consistent with AIDS, but with negative HIV testing. [...]
- Published
- 2020
- Full Text
- View/download PDF