Syndrome of CD4+ T Cell Suppression Without HIV Infection Rare, Occurs in Many Forms
The syndrome known as idiopathic CD4+ T lymphocytopenia (ICL) is rare and most likely has many causes -- but is not related to the AIDS virus -- according to two National Institute of Allergy and Infectious Diseases (NIAID) presentations scheduled for the IXth International Conference on AIDS, June 7 to 11 in Berlin.
The NIAID studies further verify previous findings that ICL is not caused by HIV-1 or HIV-2 or human T lymphotropic virus (HTLV)-I or II nor by any retrovirus, the family to which these viruses belong. Moreover, the studies conclude that ICL affects diverse groups of people who often have clinical symptoms that differ from those of patients infected with HIV.
ICL first came to public attention during the VIIIth International Conference on AIDS in Amsterdam in July 1992. On July 30, 1992, NIAID announced that it would make its network of research resources immediately available for clinical and laboratory investigations of ICL.
Several studies have since been conducted, four of which were reported in the Feb. 11 issue of The New England Journal of Medicine. Writing in an editorial in that issue, Anthony S. Fauci, M.D., director of NIAID, noted that while cases of ICL have been identified since 1983, patients who have had suppressed immune systems without known causes have been reported for decades and some of these almost certainly would have fit the current definition of ICL.
Patients have ICL if they have two or more counts of CD4+ T cells below 300 per cubic millimeter of blood (mm3) or a percentage of such cells that is less than 20 percent of the total number of white blood cells, no evidence of HIV-1 or HIV-2 infections and no defined disease or therapy that accounts for the low levels of the CD4+ T cells. During HIV infection, the virus targets and kills these crucial white blood cells of the immune system.
In a study of 24 ICL patients, NIAID scientists found counts of CD4+ T cells ranging from 12 to 343/mm3, with a midpoint of 138 and counts of CD8+ T cells, from 30 to 738/mm3 with a midpoint of 240/mm3. Of the 24 individuals, 96 percent had low numbers of CD3+ T cells.
In 16 patients, we found conditions, such as cryptoccocal disease (in six patients) or Mycobacterium avium-intracellulare (MAI) infection (in six patients), that are associated with a deficient immune system," says Judy Falloon, M.D., of NIAID's Laboratory of Immunoregulation. "In addition, none of the patients had evidence of retroviral activity." The study is scheduled for presentation on June 11.
The patients included 13 women and 11 men. Of the 24 people, 21 are white, 1 Black, 1 Hispanic and 1 Korean. They ranged in age from 25 to 84.
The second NIAID study found no persistently low CD4+ T cell counts among 2,713 HIV-uninfected gay and bisexual men enrolled in the institute's Multicenter AIDS Cohort Study (MACS).
"Among the men, we found that 99.7 percent had 300 or more CD4+ T cells/mm3 during at least four visits since 1985," says Sten H. Vermund, M.D., chief of the Vaccine and Epidemiology Branch of the institute's Division of AIDS. "Further testing revealed that the low CD4+ levels were transient in all but one man, who had an intestinal cancer treated with drugs that suppress the immune system." The study will be presented during a poster session on June 8.
MACS follows nearly 5,000 gay and bisexual men in Baltimore, Chicago, Los Angeles and Pittsburgh who are HIV-infected or are at risk for infection.
NIAID, a component of the National Institutes of Health, supports investigators and scientific studies at universities, medical schools, hospitals and research institutions in the United States and abroad aimed at preventing, diagnosing and treating such illnesses as AIDS, tuberculosis, allergy and asthma. NIH is an agency of the U.S. Public Health Service, which is part of the U.S. Department of Health and Human Services.
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