New Details on Rare Immune Disease Uncovered by NIH Researchers in 11

Sep 06, 2023

By National Institutes of Health (NIH)May 8, 2023

Scanning electron micrograph of a human T cell from the immune system of a healthy donor. In an 11-year study by the National Institutes of Health, researchers further characterized idiopathic CD4 lymphocytopenia (ICL), a rare immune deficiency that increases vulnerability to infectious diseases, autoimmune diseases, and cancers. Credit: NIAID

NIH researchers characterize ICL, a rare immune deficiency, linking severe cases to higher risk of infections and cancers.

In an 11-year study, researchers at the National Institutes of HealthThe National Institutes of Health (NIH) is the primary agency of the United States government responsible for biomedical and public health research. Founded in 1887, it is a part of the U.S. Department of Health and Human Services. The NIH conducts its own scientific research through its Intramural Research Program (IRP) and provides major biomedical research funding to non-NIH research facilities through its Extramural Research Program. With 27 different institutes and centers under its umbrella, the NIH covers a broad spectrum of health-related research, including specific diseases, population health, clinical research, and fundamental biological processes. Its mission is to seek fundamental knowledge about the nature and behavior of living systems and the application of that knowledge to enhance health, lengthen life, and reduce illness and disability." data-gt-translate-attributes="[{"attribute":"data-cmtooltip", "format":"html"}]">National Institutes of Health (NIH) have further characterized idiopathic CD4 lymphocytopenia (ICL), a rare immune deficiency that leaves people vulnerable to infectious diseases, autoimmune diseases, and cancers. Researchers observed that people with the most severe cases of ICL had the highest risk of acquiring or developing several of the diseases associated with this immune deficiency. This study, published on May 4 in the New England Journal of Medicine, was led by Irini Sereti M.D., M.H.S. and Andrea Lisco, M.D., Ph.D. of the HIV Pathogenesis Section in the Laboratory of Immunoregulation at the National Institute of Allergy and Infectious diseases (NIAID), part of NIH, and conducted at the NIH Clinical Center.

ICL is a condition marked by too few CD4+ T-cells, which are a type of white blood cell. The clinical definition of ICL is a CD4+ T-cell count of less than 300 cells per cubic millimeter (mm³) of blood for at least six weeks, in the absence of any disease or therapy associated with reduced white blood cells. Unlike HIV, a virusA virus is a tiny infectious agent that is not considered a living organism. It consists of genetic material, either DNA or RNA, that is surrounded by a protein coat called a capsid. Some viruses also have an outer envelope made up of lipids that surrounds the capsid. Viruses can infect a wide range of organisms, including humans, animals, plants, and even bacteria. They rely on host cells to replicate and multiply, hijacking the cell's machinery to make copies of themselves. This process can cause damage to the host cell and lead to various diseases, ranging from mild to severe. Common viral infections include the flu, colds, HIV, and COVID-19. Vaccines and antiviral medications can help prevent and treat viral infections." data-gt-translate-attributes="[{"attribute":"data-cmtooltip", "format":"html"}]">virus that suppresses the immune system if left untreated, there is no evidence that ICL is transmitted from person to person, and it has no known cause. There are limited therapeutic options for ICL.

In this observational study, the NIAID researchers quantified immune cells and noted the presence of opportunistic infections—infections that typically only affect people with suppressed immune systems—and other clinical conditions among 91 participant volunteers with ICL. The most prevalent opportunistic infections were human papillomavirus-related diseases (in 29% of participants), cryptococcosis (24%), molluscum contagiosum (9%), and mycobacterial diseases other than tuberculosis (5%). Participants with CD4+ T-cell counts below 100 cells per mm³ had a more than five-fold higher risk of opportunistic infections than those with CD4+ T-cell counts above 100 cells. Cancer risk was also higher in individuals with the lowest CD4+ T-cell counts, but the risk of autoimmune disease was lower.

These findings further support the inverse correlation between CD4+ T-cell count and susceptibility to viral, fungal, and mycobacterial infections, as well as certain cancers, according to the authors. NIAID continues to pursue research on the natural history of rare conditions such as ICL to understand disease progression, as well as potential therapeutic interventions.

"Reappraisal of Idiopathic CD4 Lymphocytopenia at 30 Years" by Andrea Lisco, M.D., Ph.D., Ana M. Ortega-Villa, Ph.D., Harry Mystakelis, M.D., M.H.S., Megan V. Anderson, R.N., B.A., Allyson Mateja, M.S.P.H., Elizabeth Laidlaw, P.A.-C., Maura Manion, M.D., Gregg Roby, R.N., B.S., Jeanette Higgins, Ph.D., Safia Kuriakose, Pharm.D., Magdalena A. Walkiewicz, Ph.D., Morgan Similuk, Sc.M., Jennifer W. Leiding, M.D., Alexandra F. Freeman, M.D., Virginia Sheikh, M.D. and Irini Sereti, M.D., M.H.S., 4 May 2023. New England Journal of Medicine.DOI: 10.1056/NEJMoa2202348

Andrea Lisco, M.D., Ph.D. is an assistant clinical investigator in the HIV Pathogenesis Section of NIAID's Laboratory of Immunoregulation, and Irini Sereti, M.D., M.H.S. is chief of the HIV Pathogenesis section.