Idiopathic CD4+ lymphocytopenia

Idiopathic CD4+ lymphocytopenia
Other names	Immunodeficiency 13
Idiopathic CD4+ lymphocytopenia is inherited via autosomal dominant manner[1]
Specialty	Immunology

Idiopathic CD4+ lymphocytopenia (ICL) is a rare medical syndrome in which the body has too few CD4⁺ T lymphocytes, which are a kind of white blood cell.^[2] ICL is sometimes characterized as "HIV-negative AIDS", though, in fact, its clinical presentation differs somewhat from that seen with HIV/AIDS.^[3] People with ICL have a weakened immune system and are susceptible to opportunistic infections, although the rate of infections is lower than in people with AIDS.^[4]

The cause of ICL, like all idiopathic conditions, is unknown. It does not appear to be caused by a transmissible agent, such as a virus.^[5] It is widely believed that there is more than one cause.^{[6][non-primary source needed]}

The loss of CD4+ T cells appears to be through apoptosis.^[4][7] The accelerated deaths of the T cells is likely driven by crosslinking T cell receptors.^[7]

The mandatory criteria for diagnosis of idiopathic CD4+ lymphocytopenia include:^[8]

• Low numbers of CD4+ cells, on two or more measurements over at least six weeks:
  • CD4 cell count less than 300 cells per microliter, or
  • Less than 20% of T lymphocytes are CD4+
• Laboratory evidence of lack of HIV infection
• Absence of any alternative explanation for the CD4 lymphocytopenia

A one-time finding of low CD4+ cells is usually associated with a recent infection and resolves on its own.^[7] Alternative explanations for the low CD4 counts include conditions such as blood cancers (aleukemia), treatment with chemotherapy, immunosuppressive medications, or other medications that suppress or kill T cells, infections, and problems with blood production.^{[2][9][non-primary source needed]}

All criteria must be fulfilled for a diagnosis of ICL. In addition, if these findings are present but combined with other significant findings, such as anemia or thrombocytopenia, then other diagnoses must be considered^{[citation needed]}.

Fludarabine-based hematopoietic stem cell transplantation (HSCT) has shown to be a feasible treatment for ICL.^{[10][non-primary source needed]}

In contrast to the CD4⁺ cell depletion caused by HIV, in general, patients with idiopathic CD4 lymphocytopenia have a good prognosis.^{[6][11][12][13][non-primary source needed]} The decline in CD4⁺ T-cells in patients with ICL is generally slower than that seen in HIV-infected patients.^[3] The major risk to people with ICL is unexpected infections, including cryptococcus, atypical mycobacterial and Pneumocystis jiroveci pneumonia (PCP). The condition may also resolve on its own.^[14]

ICL sometimes precedes and may be the first signal of several blood cancers. ICL patients have developed primary effusion lymphoma,^{[15][non-primary source needed][16]} primary leptomeningeal lymphoma,^[9] diffuse large cell lymphoma,^{[17][non-primary source needed]} MALT lymphoma,^[18] and Burkitt's lymphoma,^[19] among others.

ICL may indirectly trigger autoimmune diseases. It has been associated with several cases of autoimmune disease Sjögren syndrome.^[4][20]

Because all of the reported autoimmune diseases and lymphomas involve B cells, one hypothesis proposes that ICL's narrow T cell repertoire predisposes the immune system to B cell disorders.^[4]

ICL is a very rare disease.^[2] In 1993, a total of 47 confirmed cases were reported in a survey sponsored by the Centers for Disease Control.^[21]