Expanding mechanistic insights into the pathogenesis of idiopathic CD4+ T cell lymphocytopenia
Jose S. Campos, … , Sarah E. Henrickson, Roshini S. Abraham
Jose S. Campos, … , Sarah E. Henrickson, Roshini S. Abraham
Published August 31, 2020
Citation Information: J Clin Invest. 2020;130(10):5105-5108. https://doi.org/10.1172/JCI141717.
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Commentary

Expanding mechanistic insights into the pathogenesis of idiopathic CD4+ T cell lymphocytopenia

Abstract

Idiopathic CD4+ T cell lymphocytopenia (ICL) is a heterogeneous syndrome presenting with persistent CD4+ T cell lymphopenia of unknown origin, and opportunistic infections in some patients. The underlying pathogenesis and appropriate management remain understudied. In this issue of the JCI, Perez-Diez and Wong et al. assessed the prevalence of autoantibodies from the sera of 51 adult ICL patients (out of a cohort of 72). Some patients showed high levels of IgG and IgM autoantibodies against numerous autoantigens, and some autoantibodies were specific for lymphocytes. The researchers implicate these autoantibodies as a possible pathogenic mechanism responsible for the reduction in circulating CD4+ T cells. This study goes beyond defining a mechanism in a complex, poorly defined disease; it also brings a renewed focus on ICL that will likely result in improved diagnostic evaluation and treatment.

Authors

Jose S. Campos, Sarah E. Henrickson, Roshini S. Abraham

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Figure 1

Pathophysiological mechanisms in idiopathic (CD4+) T cell lymphopenia.

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Pathophysiological mechanisms in idiopathic (CD4+) T cell lymphopenia. (...
(A) Autoantibodies found in a subset of ICL patients induce peripheral CD4+ T cell destruction through antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) (14). (B) Future studies to elucidate additional mechanisms underlying ICL should focus on deep immune profiling of dysregulated immune cell subsets, (e.g., via mass cytometry [CyTOF] or other high-throughput flow cytometry methods) as well as high-throughput screening for target identification and characterization of autoantibody affinity.