Correspondence

Low CD4+ Counts in a Study of Transfusion Safety

N Engl J Med 1993; 328:441-442February 11, 1993

Article

To the Editor:

Laurence and coworkers,1 as well as others,2,3 have reported that the depletion of CD4+ T lymphocytes may be associated with AIDS-defining or other severe illnesses in persons without identifiable human immunodeficiency virus (HIV) infection (those with idiopathic CD4+ T-lymphocytopenia)4. Although obviously uncommon, this event and the possibility that a new virus could be transmitted by blood transfusion or clotting-factor concentrates have caused great concern.

Data concerning CD4+ counts have been collected by the Transfusion Safety Study at six-month intervals for persons at risk for HIV infection and for control populations since August 1985. Six sites performed lymphocyte immunophenotyping according to standardized protocols, with quality control monitored by interlaboratory and intralaboratory immunologic methods5. The persons evaluated have come from various populations exposed to blood components, pooled-plasma derivatives, or both; specific control populations for each category of subjects; and those at possible risk because of long-term sexual or household exposure to subjects with transfusion-acquired infections6,7.

For persons who were initially anti-HIV-negative, HIV status has been monitored at each visit. Persons exposed directly to blood components or plasma derivatives had at least one serum sample tested by Western immunoblot assay. Subjects with the greatest exposure to blood components were also evaluated by viral culture, the polymerase-chain-reaction assay, or both.

To ensure comparability with other reports, the criteria proposed by the Centers for Disease Control and Prevention (CDC) for the case definition of CD4+ T-lymphocytopenia were used4: CD4+ counts of less than 300 cells per cubic millimeter on two or more occasions, no evidence of HIV infection, and the absence of any condition associated with immunodeficiency or therapy that induces T-cell depletion.

Of the 4018 persons enrolled in the study, 2192 were not infected with HIV and had at least two lymphocyte profiles determined. Thirty-two persons had CD4+ counts of less than 300 cells per cubic millimeter on at least two occasions, for a prevalence of 1.5 percent (Table 1Table 1Frequency of Low CD4+ Cell Counts among Subjects without HIV Infection.). Of these, 20 were known to have conditions or to have received treatments often associated with low CD4+ counts, including metastatic tumors and the administration of corticosteroids and cytotoxic drugs. We saw no instances of AIDS-defining illness according to the 1987 CDC criteria,8 either in the 20 persons with a known potential cause for a low CD4+ count or in the 12 who had none of the usual causes.

The most important observation in this large study is that in the past seven years, the phenomenon of low CD4+ counts has not tended to occur more frequently among persons exposed to blood components than among those who were not so exposed.

Louis M. Aledort, M.D.
Mount Sinai Medical Center, New York, NY 10029

Eva A. Operskalski, Ph.D.
University of Southern California School of Medicine, Los Angeles, CA 90032

Shelby L. Dietrich, M.D.
Huntington Memorial Hemophilia Center, Pasadena, CA 91105

Marion A. Koerper, M.D.
University of California, San Francisco, San Francisco, CA 94143

George F. Gjerset, M.D.
Puget Sound Blood Center, Seattle, WA 98104

Jeanne M. Lusher, M.D.
Wayne State University, Detroit, MI 48201

Eric C.Y. Lian, M.D.
University of Miami School of Medicine, Miami, FL 33101

James W. Mosley, M.D.
University of Southern California School of Medicine, Los Angeles, CA 90032

The Transfusion Safety Study Group

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Citing Articles (14)

Citing Articles

1. 1

   T. W. Kuijpers, H. IJspeert, E. M. M. van Leeuwen, M. H. Jansen, M. D. Hazenberg, K. C. Weijer, R. A. W. van Lier, M. van der Burg. (2011) Idiopathic CD4+ T lymphopenia without autoimmunity or granulomatous disease in the slipstream of RAG mutations. Blood 117:22, 5892-5896
   CrossRef

2. 2

   T. Trojan, R. Collins, D. A. Khan. (2009) Safety and efficacy of treatment using interleukin-2 in a patient with idiopathic CD4 ⁺ lymphopenia and Mycobacterium avium-intracellulare. Clinical & Experimental Immunology 156:3, 440-445
   CrossRef

3. 3

   D. I. Zonios, J. Falloon, J. E. Bennett, P. A. Shaw, D. Chaitt, M. W. Baseler, J. W. Adelsberger, J. A. Metcalf, M. A. Polis, S. J. Kovacs, J. A. Kovacs, R. T. Davey, H. C. Lane, H. Masur, I. Sereti. (2008) Idiopathic CD4+ lymphocytopenia: natural history and prognostic factors. Blood 112:2, 287-294
   CrossRef

4. 4

   Simha Jagadeesh, Bharti Asnani, Roger E. Nieman. (2008) Opportunistic Infections in Persons With Idiopathic CD4 Lymphocytopenia. Infectious Diseases in Clinical Practice 16:4, 218-221
   CrossRef

5. 5

   Paula J. Busse, Charlotte Cunningham-Rundles. (2002) Primary leptomeningeal lymphoma in a patient with concomitant CD4+ lymphocytopenia. Annals of Allergy, Asthma & Immunology 88:3, 339-342
   CrossRef

6. 6

   ROBERT F. GARRY, CÉSAR D. FERMIN, PETER F. KOHLER, M. LOUISE MARKERT, HONG LUO. (1996) Antibodies against Retroviral Proteins and Nuclear Antigens in a Subset of Idiopathic CD4 ⁺ T Lymphocytopenia Patients. AIDS Research and Human Retroviruses 12:10, 931-940
   CrossRef

7. 7

   Thomas R. O'Brien, Laura Diamondstone, Michael W. Fried, Louis M. Aledort, Sabine Eichinger, M. Elaine Eyster, Margaret W. Hilgartner, Gilbert White, Adrian M. Di Bisceglie, James J. Goedert. (1995) Idiopathic CD4+ T-lymphocytopenia in HIV seronegative men with hemophilia and sex partners of HIV seropositive men. American Journal of Hematology 49:3, 201-206
   CrossRef

8. 8

   Dianne Vertes, Michael D. Linden, John L. Carey. (1995) Idiopathic CD4 + T-lymphocytopenia: Analysis of a patient with selective IgA deficiency and no evidence of HIV infection. Cytometry 22:1, 40-44
   CrossRef

9. 9

   (1993) CD4+ T-Lymphocytopenia without HIV Infection. New England Journal of Medicine 328:25, 1847-1850
   Full Text

10. 10

    Mosley, James W., . (1993) Low CD4+ Counts in a Study of Transfusion Safety: Correction. New England Journal of Medicine 328:15, 1128-1128
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11. 11

    Spira, Thomas J.Jones, Bonnie M.Nicholson, JanetLal, Renu B.Rowe, ThomasMawle, Alison C.Lauter, Carl B.Shulman, Jonas A.Monson, Roberta A.. (1993) Idiopathic CD4+ T-Lymphocytopenia -- An Analysis of Five Patients with Unexplained Opportunistic Infections. New England Journal of Medicine 328:6, 386-392
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12. 12

    Vermund, Sten H., , Hoover, Donald R., Chen, Kan, . (1993) CD4+ Counts in Seronegative Homosexual Men. New England Journal of Medicine 328:6, 442-442
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13. 13

    Fauci, Anthony S., . (1993) CD4+ T-Lymphocytopenia without HIV Infection -- No Lights, No Camera, Just Facts. New England Journal of Medicine 328:6, 429-431
    Full Text

14. 14

    Smith, Dawn K.Neal, Joyce J.Holmberg, Scott D.the Centers for Disease Control Idiopathic CD4+ T-Lymphocytopenia Task Force. (1993) Unexplained Opportunistic Infections and CD4+ T-Lymphocytopenia without HIV Infection -- An Investigation of Cases in the United States. New England Journal of Medicine 328:6, 373-379
    Full Text

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