Background The human immunodeficiency virus (HIV), the etiologicagent of the acquired immunodeficiency syndrome (AIDS), infectsand depletes CD4+ T lymphocytes. Recently, patients have beendescribed with profound CD4+ T-lymphocytopenia but without evidentHIV infection, a condition now termed idiopathic CD4+ T-lymphocytopenia,and a national surveillance network has been set up to investigatesuch cases.
Methods We studied 12 patients with CD4+ T-lymphocytopenia whowere referred to us from three U.S. cities. Blood samples weretested for HIV with specific antibody assays, viral cultures,and polymerase-chain-reaction (PCR) techniques.
Results The patients (10 men and 2 women) ranged in age from30 to 69 years. Eight had risk factors for HIV infection. Theclinical manifestations were heterogeneous: five patients hadopportunistic infections, five had syndromes of unknown cause,and two had no symptoms. Two patients died from acute complicationsof their immunodeficiency. The patients' lowest CD4+ lymphocytecounts ranged from 3 to 308 per cubic millimeter (mean, 149).Three patients had complete or partial spontaneous reversalof the CD4+ T-lymphocytopenia. Concomitant CD8+ T-lymphocytopeniawas noted in three patients, and abnormal immunoglobulin levelswere found in five. Multiple virologic studies by serologictesting, culture, and PCR were completely negative for HIV inall patients.
Conclusions Our 12 patients with idiopathic CD4+ T-lymphocytopeniaappear to be epidemiologically, clinically, and immunologicallyheterogeneous. It is unclear whether this syndrome is new, transmissible,or acquired. Many of the clinical and immunologic features aredistinct from those found in AIDS, and our extensive virologicstudies found no evidence of HIV infection. The cause of thiscondition remains unknown.
Source Information
From the Aaron Diamond AIDS Research Center (D.D.H., Y.C., T.Z., N.W., G.G.) and the New York University School of Medicine (D.D.H., C.F.), New York; the Division of Infectious Diseases, University of Colorado Health Sciences Center, Denver (R.T.S.); and the Division of Infectious Diseases, Department of Medicine, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles (E.S.D.).
Address reprint requests to Dr. Ho at the Aaron Diamond AIDS Research Center, New York University School of Medicine, 455 First Ave., New York, NY 10016.
Zonios, D. I., Falloon, J., Bennett, J. E., Shaw, P. A., Chaitt, D., Baseler, M. W., Adelsberger, J. W., Metcalf, J. A., Polis, M. A., Kovacs, S. J., Kovacs, J. A., Davey, R. T., Lane, H. C., Masur, H., Sereti, I.
(2008). Idiopathic CD4+ lymphocytopenia: natural history and prognostic factors. Blood
112: 287-294
[Abstract][Full Text]
Voisset, C., Weiss, R. A., Griffiths, D. J.
(2008). Human RNA "Rumor" Viruses: the Search for Novel Human Retroviruses in Chronic Disease. Microbiol. Mol. Biol. Rev.
72: 157-196
[Abstract][Full Text]
Malaspina, A., Moir, S., Chaitt, D. G., Rehm, C. A., Kottilil, S., Falloon, J., Fauci, A. S.
(2007). Idiopathic CD4+ T lymphocytopenia is associated with increases in immature/transitional B cells and serum levels of IL-7. Blood
109: 2086-2088
[Abstract][Full Text]
Wladis, E. J., Kapila, R., Chu, D. S.
(2005). Idiopathic CD4+ Lymphocytopenia and Sjogren Syndrome. Arch Ophthalmol
123: 1012-1012
[Full Text]
Kilic, S S., Bostan, O, Cil, E
(2002). Takayasu arteritis. Ann Rheum Dis
61: 92-93
[Full Text]
Hubert, P., Bergeron, F., Ferreira, V., Seligmann, M., Oksenhendler, E., Debre, P., Autran, B.
(2000). Defective p56Lck activity in T cells from an adult patient with idiopathic CD4+ lymphocytopenia. Int Immunol
12: 449-457
[Abstract][Full Text]
Iwase, T., Ojika, K., Katada, E., Mitake, S., Nakazawa, H., Matsukawa, N., Otsuka, Y., Tsugu, Y., Kanai, H., Nakajima, K.
(1998). An unusual course of progressive multifocal leukoencephalopathy in a patient with idiopathic CD4+ T lymphocytopenia. J. Neurol. Neurosurg. Psychiatry
64: 788-791
[Abstract][Full Text]
Fernandez-Cruz, E., Zabay, J. M., Munoz-Fernandez, M. d. l. A.
(1996). Idiopathic CD4+ T-Lymphocytopenia in an Asymptomatic HIV-Seronegative Woman after Exposure to HIV. NEJM
334: 1202-1203
[Full Text]
Rezza, G, Pezzotti, P, Aiuti, F
(1995). Acquired immunodeficiency without HIV infection: epidemiology and clinical outcome in Italy. BMJ
311: 785-786
[Full Text]
Monteil, M A, Henderson, D C, Obaro, S, Dev, D, Basran, G S, Slater, D, Taylor, P, Wood, M
(1994). Immunodeficiency without HIV Clinical presentations vary. BMJ
308: 1436-1436
[Full Text]
Holland, S. M., Eisenstein, E. M., Kuhns, D. B., Turner, M. L., Fleisher, T. A., Strober, W., Gallin, J. I.
(1994). Treatment of Refractory Disseminated Nontuberculous Mycobacterial Infection With Interferon Gamma: A Preliminary Report. NEJM
330: 1348-1355
[Abstract][Full Text]
DeHovitz, J. A., Feldman, J., Landesman, S.
(1993). Idiopathic CD4+ T-Lymphocytopenia. NEJM
329: 1045-1046
[Full Text]
Sheppard, H., Winkelstein, W., Lang, W., Charlebois, E., Heymann, D. L., Belsey, E., Esparza, J. G., Laurence, J., Corboy, J. R., Stevens, S. R., Griffiths, T. W., Cooper, K. D., Smith, D. K., Neal, J. J., Holmberg, S. D.
(1993). CD4+ T-Lymphocytopenia without HIV Infection. NEJM
328: 1847-1850
[Full Text]
(1993). Putting the 'New' AIDS-Like Illness in Perspective. Journal Watch Dermatology
1993: 18-18
[Full Text]
(1993). PUTTING THE ""NEW"" AIDS-LIKE ILLNESS IN PERSPECTIVE. JWatch General
1993: 1-1
[Full Text]
Smith, D. K., Neal, J. J., Holmberg, S. D., The Centers for Disease Control Idiopathic CD4+ T-,
(1993). Unexplained Opportunistic Infections and CD4+ T-Lymphocytopenia without HIV Infection -- An Investigation of Cases in the United States. NEJM
328: 373-379
[Abstract][Full Text]
Fauci, A. S.
(1993). CD4+ T-Lymphocytopenia without HIV Infection -- No Lights, No Camera, Just Facts. NEJM
328: 429-431
[Full Text]