Idiopathic CD4 Lymphocytopenia
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Idiopathic CD4+ lymphocytopenia (ICL) is a rare medical
syndrome A syndrome is a set of medical signs and symptoms which are correlated with each other and often associated with a particular disease or disorder. The word derives from the Greek language, Greek σύνδρομον, meaning "concurrence". When a sy ...
in which the body has too few
CD4 In molecular biology, CD4 (cluster of differentiation 4) is a glycoprotein that serves as a co-receptor for the T-cell receptor (TCR). CD4 is found on the surface of immune cells such as helper T cells, monocytes, macrophages, and dendritic c ...
+
T lymphocytes T cells (also known as T lymphocytes) are an important part of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes A lymphocyte is a type of white blood cell (leukoc ...
, which are a kind of
white blood cell White blood cells (scientific name leukocytes), also called immune cells or immunocytes, are cells of the immune system that are involved in protecting the body against both infectious disease and foreign entities. White blood cells are genera ...
. ICL is sometimes characterized as "HIV-negative AIDS", though, in fact, its clinical presentation differs somewhat from that seen with HIV/AIDS. People with ICL have a
weakened immune system Immunodeficiency, also known as immunocompromise, is a state in which the immune system's ability to fight infectious diseases and cancer is compromised or entirely absent. Most cases are acquired ("secondary") due to extrinsic factors that affec ...
and are susceptible to
opportunistic infection An opportunistic infection is an infection that occurs most commonly in individuals with an immunodeficiency disorder and acts more severe on those with a weakened immune system. These types of infections are considered serious and can be caused b ...
s, although the rate of infections is lower than in people with
AIDS The HIV, human immunodeficiency virus (HIV) is a retrovirus that attacks the immune system. Without treatment, it can lead to a spectrum of conditions including acquired immunodeficiency syndrome (AIDS). It is a Preventive healthcare, pr ...
.


Cause

The cause of ICL, like all
idiopathic An idiopathic disease is any disease with an unknown cause or mechanism of apparent spontaneous origin. For some medical conditions, one or more causes are somewhat understood, but in a certain percentage of people with the condition, the cause ...
conditions, is unknown. It does not appear to be caused by a transmissible agent, such as a
virus A virus is a submicroscopic infectious agent that replicates only inside the living Cell (biology), cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Viruses are ...
. It is widely believed that there is more than one cause.


Pathophysiology

The loss of CD4+ T cells appears to be through
apoptosis Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...
. The accelerated deaths of the T cells is likely driven by crosslinking T cell receptors.


Diagnosis

The mandatory criteria for diagnosis of idiopathic CD4+ lymphocytopenia include: * 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 Lymphocytopenia is the condition of having an abnormally low level of lymphocytes in the blood. Lymphocytes are a white blood cell with important functions in the immune system. It is also called lymphopenia. The opposite is lymphocytosis, which r ...
A one-time finding of low CD4+ cells is usually associated with a recent infection and resolves on its own. Alternative explanations for the low CD4 counts include conditions such as
blood cancer Tumors of the hematopoietic and lymphoid tissues (American English) or tumours of the haematopoietic and lymphoid tissues (British English) are tumors that affect the blood, bone marrow, lymph, and lymphatic system. Because these tissues are al ...
s ( aleukemia), treatment with
chemotherapy Chemotherapy (often abbreviated chemo, sometimes CTX and CTx) is the type of cancer treatment that uses one or more anti-cancer drugs (list of chemotherapeutic agents, chemotherapeutic agents or alkylating agents) in a standard chemotherapy re ...
, immunosuppressive medications, or other medications that suppress or kill
T cell T cells (also known as T lymphocytes) are an important part of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell receptor (TCR) on their cell ...
s, infections, and problems with blood production. 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 Anemia (also spelt anaemia in British English) is a blood disorder in which the blood has a reduced ability to carry oxygen. This can be due to a lower than normal number of red blood cells, a reduction in the amount of hemoglobin availabl ...
or
thrombocytopenia In hematology, thrombocytopenia is a condition characterized by abnormally low levels of platelets (also known as thrombocytes) in the blood. Low levels of platelets in turn may lead to prolonged or excessive bleeding. It is the most common coag ...
, then other diagnoses must be considered.


Treatment

Fludarabine-based
hematopoietic stem cell transplantation Hematopoietic stem-cell transplantation (HSCT) is the transplantation of multipotent hematopoietic stem cells, usually derived from bone marrow, peripheral blood, or umbilical cord blood, in order to replicate inside a patient and produce ...
(HSCT) has shown to be a feasible treatment for ICL.


Prognosis

In contrast to the CD4+ cell depletion caused by HIV, in general, patients with idiopathic CD4 lymphocytopenia have a good
prognosis Prognosis ( Greek: πρόγνωσις "fore-knowing, foreseeing"; : prognoses) is a medical term for predicting the likelihood or expected development of a disease, including whether the signs and symptoms will improve or worsen (and how quickly) ...
. The decline in CD4+ T-cells in patients with ICL is generally slower than that seen in HIV-infected patients. The major risk to people with ICL is unexpected infections, including cryptococcus, atypical
mycobacterial ''Mycobacterium'' is a genus of over 190 species in the phylum Actinomycetota, assigned its own family, Mycobacteriaceae. This genus includes pathogens known to cause serious diseases in mammals, including tuberculosis ('' M. tuberculosis'') an ...
and Pneumocystis jiroveci pneumonia ( PCP). The condition may also resolve on its own. ICL sometimes precedes and may be the first signal of several blood cancers. ICL patients have developed primary effusion lymphoma, primary leptomeningeal lymphoma, diffuse large cell lymphoma,
MALT lymphoma MALT lymphoma (also called MALToma) is a form of lymphoma involving the mucosa-associated lymphoid tissue (MALT), frequently of the stomach, but virtually any mucosal site can be affected. It is a cancer originating from B cells in the marginal zon ...
, and
Burkitt's lymphoma Burkitt's lymphoma is a cancer of the lymphatic system, particularly B lymphocytes found in the germinal center. It is named after Denis Parsons Burkitt, the Irish surgeon who first described the disease in 1958 while working in equatorial Africa ...
, among others. ICL may indirectly trigger autoimmune diseases. It has been associated with several cases of autoimmune disease
Sjögren syndrome Sjögren is a Swedish surname. Notable people with the surname include: * Anders Johan Sjögren (1794–1855), Finnish linguist, historian, ethnographer and explorer * Ann Mari Sjögren, Swedish fantasy artist and illustrator * Christer Sjögren, ...
. Because all of the reported autoimmune diseases and lymphomas involve
B cell B cells, also known as B lymphocytes, are a type of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted or inserted into the plasm ...
s, one hypothesis proposes that ICL's narrow T cell repertoire predisposes the immune system to B cell disorders.


Epidemiology

ICL is a very
rare disease A rare disease is any disease that affects a small percentage of the population. In some parts of the world, the term orphan disease describes a rare disease whose rarity results in little or no funding or research for treatments, without financi ...
. In 1993, a total of 47 confirmed cases were reported in a survey sponsored by the
Centers for Disease Control The Centers for Disease Control and Prevention (CDC) is the national public health agency of the United States. It is a United States federal agency under the Department of Health and Human Services (HHS), and is headquartered in Atlanta, ...
.


References


External links

{{Lymphoid immunodeficiency Rare diseases Immune system disorders Immunodeficiency