Page 43 - AIDSBK23C

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IDIOPATHIC CD4+ T-LYMPHOCYTOPENIA

Increased laboratory testing in patients with immunodeficiency states has led to the recognition
that CD4 lymphocyte counts in some cases can be markedly decreased in the absence of
laboratory evidence for HIV infection. These uncommon, sporadically reported cases are
unlikely to represent infection by new HIV subtypes that are not detectable by current laboratory
testing methods. Criteria for diagnosis of ICL include:

* The absolute CD4 lymphocyte count is <300/µL or more in adults and children >2
years (<1000/µL in children <2 years) on more than one determination, or in
children a T-lymphocyte count that is <20% of total lymphocytes; and
* There is no serologic evidence for HIV infection (even if in a child and the
mother is HIV seropositive); and
* There is no defined immunodeficiency or therapy associated with T-cell depletion

Though some patients with ICL may have a risk factor for HIV infection or even an
opportunistic infection, the CD4 lymphocyte count does not progressively decrease over time as
with AIDS. Almost all patients with ICL have normal serum immunoglobulin levels. The initial
CD4/CD8 ratio is <1 in 85% of cases. The stable CD4 lymphocyte counts may be accompanied
by reductions in the levels of other lymphocyte subsets, including CD8+ T-lymphocytes, natural
killer cells, and B-lymphocytes. This disorder appears to be rare and is generally associated with
transient illness. The presence of ICL does not constitute evidence for a new transmissible
infectious agent.[238,239] A Behçet-like syndrome has been reported in conjunction with
ICL.[240]
Most ICL patients will present in middle age with an opportunistic infection. The most
common opportunistic infections with ICL are cryptococcosis, human papillomavirus, and
nontuberculous mycobacteria. Less common infections include histoplasmosis, mucosal
candidiasis, herpes zoster, Pneumocystis pneumonia, and cytomegalovirus pneumonia. About a
fourth of ICL patients have an autoimmune disease at some point in the course of their disease,
including such conditions as systemic lupus erythematosus, antiphospholipid syndrome, Graves
disease, autoimmune hemolytic anemia, ulcerative colitis, psoriasis, vitiligo, and thyroiditis.
About a fifth of patients have resolution of lymphocytopenia after three years.[241]
Molecular studies have shown that ICL is associated with a defect in CXCR4 expression
on the surface of CD4 lymphocytes. There is abnormal intracellular accumulation of CXCR4
and of its natural ligand, the chemokine CXCL12. This abnormality reduced the CD4 cell
chemotactic response to CXCL12 but preserved CXCL8 sensitivity. Administration of IL-2
reversed the defect.[242] There is increased CD4 cell activation and increased turnover that may
represent an abnormal response to a triggering infection.[241]