Correspondence

Idiopathic CD4+ T-Lymphocytopenia in an Asymptomatic HIV-Seronegative Woman after Exposure to HIV

N Engl J Med 1996; 334:1202-1203May 2, 1996

Article

To the Editor:

CD4+ T-lymphocytopenia is extremely rare in the absence of human immunodeficiency virus (HIV) infection in asymptomatic persons.1,2 For more than five years we have followed a 30-year-old woman with depletion of CD4+ T lymphocytes who had repeated unprotected sexual contact with an HIV-infected man in whom AIDS later developed. She has not reported intravenous drug use and has received no blood transfusions or therapies known to be associated with T-cell depletion. She has remained asymptomatic.

Serologic tests for antibodies to HIV types 1 and 2 (enzyme-linked immunosorbent assays [ELISAs]: recombinant HIV-1 Anticore EIA and HIV-1/HIV-2 EIA Plus [Abbott]; and Western blot assays: LAV.Blot and Pepti LAV I II [Pasteur]) were repeatedly negative. Cultures of the patient's peripheral-blood mononuclear cells3 were repeatedly negative for the formation of syncytia and for HIV p24 antigen and reverse transcriptase activity in the culture supernatants. Serial polymerase-chain-reaction (PCR) assays4 to detect HIV proviral DNA in peripheral-blood mononuclear cells were negative. Also, no DNA sequences related to human T-cell lymphotropic virus (HTLV) type I or II were detected by PCR, and no antibodies to HTLV-I or HTLV-II were found by ELISA (Abbott HTLV-I 2.0 EIA) or the Western blot assay (Bioblot HTLV [V.3], Biokit). Tests for antibodies to cytomegalovirus, Epstein–Barr virus, herpes simplex virus, varicella–zoster virus, hepatitis B and C viruses, Treponema pallidum, toxoplasma, and leishmania have repeatedly been negative, as well as tests for hepatitis B surface and cryptococcal antigens. A skin-test challenge with Mycobacterium tuberculosis purified protein derivative was negative. CD4+ counts below 300 cells per cubic millimeter (range, 143 to 288) were found on five determinations (Figure 1Figure 1Serial Determinations of CD4+ and CD8+ T-Lymphocyte Counts by Flow Cytometry.). Our patient's condition meets the definition of idiopathic CD4+ T-lymphocytopenia formulated by the Centers for Disease Control and Prevention.1

She has had normal levels of the serum activation markers IgA and beta₂-microglobulin. Tests for antinuclear and antilymphocyte antibodies have been negative. When the patient had a CD4+ count of 277 cells per cubic millimeter, the expression of activation and memory antigens on CD4+ and CD8+ lymphocytes was normal. The lymphocyte-transformation responses to mitogens (phytohemagglutinin, concanavalin A, and pokeweed mitogen) were normal. However, a defect in delayed hypersensitivity was revealed by negative skin tests with a panel of recall antigens.5

The fact that our patient has had repeated sexual contact with an HIV-infected man before the development of idiopathic CD4+ T-lymphocytopenia raises the possibility of the involvement of HIV in her asymptomatic immunodeficiency.

Eduardo Fernández-Cruz, M.D.
José Marìa Zabay, M.D.
Maria de los Angeles Muñoz-Fernández, Ph.D.
Hospital General Universitario “Gregorio Marañón”, 28007 Madrid, Spain

5 References

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   Busch MP, Valinsky JE, Paglieroni T, et al. Screening of blood donors for idiopathic CD4+ T-lymphocytopenia. Transfusion 1994;34:192-197
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   Erice A, Sannerud KJ, Leske VL, Aeppli D, Balfour HH Jr. Sensitive microculture method for isolation of human immunodeficiency virus type 1 from blood leukocytes. J Clin Microbiol 1992;30:444-448
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   Muñoz-Fernández MA, Navarro J, García Montes M, Cosín J, Zabay JM, Fernández-Cruz E. Quantification of low levels of human immunodeficiency virus (HIV) type 1 RNA in p24 antigen-negative, asymptomatic, HIV-positive patients by PCR. J Clin Microbiol (in press).
   

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   Fernandez-Cruz E, Desco M, Garcia Montes M, Longo N, Gonzalez B, Zabay JM. Immunological and serological markers predictive of progression to AIDS in a cohort of HIV-infected drug users. AIDS 1990;4:987-994
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Citing Articles (1)

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1. 1

   Francisco A. Bonilla, I. Leonard Bernstein, David A. Khan, Zuhair K. Ballas, Javier Chinen, Michael M. Frank, Lisa J. Kobrynski, Arnold I. Levinson, Bruce Mazer, Robert P. Nelson, Jordan S. Orange, John M. Routes, William T. Shearer, Ricardo U. Sorensen. (2005) Practice parameter for the diagnosis and management of primary immunodeficiency. Annals of Allergy, Asthma & Immunology 94:5, S1-S63
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