Susceptibility to Cryptococcal Meningoencephalitis Associated With Idiopathic CD4+ Lymphopenia and Secondary Germline or Acquired Defects

Anil A Panackal; Lindsey B Rosen; Gulbu Uzel; Michael J Davis; Guowu Hu; Adebowale Adeyemo; Fasil Tekola-Ayele; Andrea Lisco; Christopher Diachok; Jonathan D Kim; Dawn Shaw; Irini Sereti; Jennifer Stoddard; Julie Niemela; Sergio D Rosenzweig; John E Bennett; Peter R Williamson

doi:10.1093/ofid/ofx082

Susceptibility to Cryptococcal Meningoencephalitis Associated With Idiopathic CD4⁺ Lymphopenia and Secondary Germline or Acquired Defects

Open Forum Infect Dis. 2017 Jun 7;4(2):ofx082. doi: 10.1093/ofid/ofx082. eCollection 2017 Spring.

Authors

Anil A Panackal^{1

2}, Lindsey B Rosen¹, Gulbu Uzel¹, Michael J Davis¹, Guowu Hu¹, Adebowale Adeyemo³, Fasil Tekola-Ayele⁴, Andrea Lisco⁵, Christopher Diachok¹, Jonathan D Kim¹, Dawn Shaw⁶, Irini Sereti⁵, Jennifer Stoddard⁷, Julie Niemela⁷, Sergio D Rosenzweig⁷, John E Bennett^{1

2}, Peter R Williamson¹

Affiliations

¹ Laboratory of Clinical Infectious Diseases, Division of Intramural Research (DIR), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH).
² Division of Infectious Diseases, Department of Medicine, F. Hebert School of Medicine, Uniformed Services University of the Health Sciences.
³ Center for Research on Genomics and Global Health, National Human Genome Research Institute, NIH.
⁴ Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, Maryland.
⁵ Laboratory of Immunoregulation, DIR, NIAID, NIH.
⁶ Leidos Biomedical Research, Inc., Frederick, Maryland.
⁷ Immunology Service, Department of Laboratory Medicine, Clinical Center, NIH, Bethesda, Maryland.

Abstract

Idiopathic CD4⁺ lymphopenia (ICL) predisposes to opportunistic infections (OIs) but can often remain asymptomatic and does not have a strong association with monogenic mutations. Likewise, cryptococcal meningoencephalitis, the most common OI in ICL, is not strongly associated with monogenic mutations. In this study, we describe 2 patients with ICL plus an additional immune defect: one from an E57K genetic mutation in the nuclear factor-κβ essential modulator, and the other with acquired autoantibodies to granulocyte-macrophage colony-stimulating factor. Thus, these cases may exemplify a "multi-hit model" in patients with ICL who acquire OIs.

Keywords: Cryptococcus; autoantibody; idiopathic CD4+ lymphopenia.; meningoencephalitis.

Grants and funding

U01 AI109657/AI/NIAID NIH HHS/United States