Irini Sereti, United States of America
National Institutes of Health National Institute of Allergy and Infectious DiseasesPresenter of 1 Presentation
PREVALENCE AND PATHOGENICITY OF AUTOANTIBODIES IN IDIOPATHIC CD4 LYMPHOPENIA
Abstract
Background and Aims
Idiopathic CD4 lymphopenia (ICL) is a heterogenous condition of unknown etiology defined by persistent low CD4 counts (<300 cells/µL), after excluding any infection or condition known to cause lymphopenia. Autoimmune diseases have been reported in ICL but it is unclear whether autoimmunity plays a role in pathogenesis. We aimed to investigate the prevalence and potential pathogenicity of autoantibodies in ICL.
Methods
We evaluated 72 patients with ICL and healthy controls (HC) of similar age and sex. Autoantibodies (IgG and IgM) were measured by a protoarray against 124 know targets. The ability of sera to bind lymphocytes was tested by flow cytometry. ADCC and CDC experiments were performed to evaluate function (cytotoxicity) of autoantibodies.
Results
ICL patient sera tested positive for a large number of IgG and IgM autoantibodies at >2-fold level (p<0.0004) compared to HC independent of autoimmune disease status and exhibited higher autoreactivity to many targets across the human proteome. 31% sera had IgG antibodies (mostly IgG1 and/or IgG4) and 29% had IgM that remained stable over time and could bind healthy control T lymphocytes. Functionally, plasma from 50% of patients with IgG1 or IgG3 autoantibodies induced ADCC against healthy T-lymphocytes. Sera from 20% of patients with anti-lymphocyte antibodies induced complement deposition on healthy T cells and 1/3 of these induced CDC. Complement deposition on T lymphocytes was observed in 14% of the patients directly ex vivo.
Conclusions
We report a high prevalence and pathogenicity of autoantibodies in ICL that may hinder recovery from lymphopenia and represent a potential therapeutic target.