Humoral immune deficiency
Encyclopedia
Humoral immune deficiencies are conditions which cause impairment of humoral immunity
Humoral immunity
The Humoral Immune Response is the aspect of immunity that is mediated by secreted antibodies produced in the cells of the B lymphocyte lineage . B Cells transform into plasma cells which secrete antibodies...

, which can lead to immunodeficiency
Immunodeficiency
Immunodeficiency is a state in which the immune system's ability to fight infectious disease is compromised or entirely absent. Immunodeficiency may also decrease cancer immunosurveillance. Most cases of immunodeficiency are acquired but some people are born with defects in their immune system,...

. It can be mediated by insufficient number or function of B cell
B cell
B cells are lymphocytes that play a large role in the humoral immune response . The principal functions of B cells are to make antibodies against antigens, perform the role of antigen-presenting cells and eventually develop into memory B cells after activation by antigen interaction...

s, the plasma cell
Plasma cell
Plasma cells, also called plasma B cells, plasmocytes, and effector B cells, are white blood cells which produce large volumes of antibodies. They are transported by the blood plasma and the lymphatic system...

s they differentiate into (with these two potentially being caused by B cell lymphocytopenia
Lymphocytopenia
Lymphocytopenia, or lymphopenia, 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...

), or the antibody
Antibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...

 secreted by the plasma cells.

They are associated with increased vulnerability to infection, but can be difficult to detect (or asymptomatic) in the absence of infection.

They can be associated with increased risk of gastric cancer.

Causes

One way of classifying humoral immune deficiencies are into primary (or hereditary) versus secondary (or acquired) ones.

Primary

The International Union of Immunological Societies
International Union of Immunological Societies
The International Union of Immunological Societies, a member of the International Council for Science, is an organization which serves as an umbrella organization for many national immunological societies. The organization was founded in 1969....

 classifies primary immune deficiencies of the humoral system (here termed "Predominantly antibody deficiencies") as follows:
  1. Absent B cells with a resultant severe reduction of all types of antibody: X-linked agammaglobulinemia
    X-linked agammaglobulinemia
    X-linked agammaglobulinemia is a rare X-linked genetic disorder that was discovered in 1952 which affects the body's ability to fight infection. XLA is an X-linked disorder, and therefore is more common in males...

     (btk
    Bruton's tyrosine kinase
    Bruton's tyrosine kinase is a type of kinase enzyme implicated in the primary immunodeficiency disease X-linked agammaglobulinemia . Its exact mechanism of action remains unknown, but it plays a crucial role in B cell maturation as well as mast cell activation through the high-affinity IgE receptor...

     deficiency, or Bruton
    Ogden Bruton
    Ogden Carr Bruton was a pediatrician and chief of pediatrics at Walter Reed Army Hospital, where he organized the first pediatric residency at this hospital...

    's agammaglobulinemia), μ
    Immunoglobulin M
    Immunoglobulin M, or IgM for short, is a basic antibody that is produced by B cells. It is the primary antibody against A and B antigens on red blood cells. IgM is by far the physically largest antibody in the human circulatory system...

    -Heavy chain
    Heavy chain
    ]The immunoglobulin heavy chain is the large polypeptide subunit of an antibody .A typical antibody is composed of two immunoglobulin heavy chains and two Ig light chains. Several different types of heavy chain exist that define the class or isotype of an antibody. These heavy chain types vary...

     deficiency, l 5
    Immunoglobulin light chain
    ]The immunoglobulin light chain is the small polypeptide subunit of an antibody .A typical antibody is composed of two immunoglobulin heavy chains and two Ig light chains.-In humans:...

     deficiency, Igα
    CD79
    CD79 is a transmembrane protein that forms a complex with the B-cell receptor and generates a signal following recognition of antigen by the BCR...

     deficiency, BLNK deficiency, thymoma with immunodeficiency
    Thymoma with immunodeficiency
    Thymoma with immunodeficiency is a condition that occurs in adults in whom hypogammaglobulinemia, deficient cell-mediated immunity, and benign thymoma may develop almost simultaneously....

  2. B cells low but present or normal, but with reduction in 2 or more isotypes (usually IgG & IgA, sometimes IgM): common variable immunodeficiency
    Common variable immunodeficiency
    Common variable immunodeficiency is a group of approximately 150 primary immunodeficiencies , which have a common set of symptoms but which have different underlying causes.Common variable immunodeficiency is the most commonly encountered primary immunodeficiency.-Causes and types:CVID...

     (CVID), ICOS deficiency, CD19
    CD19
    B-lymphocyte antigen CD19 also known as CD19 , is a protein that in humans is encoded by the CD19 gene.- Function :...

     deficiency, TACI
    Tumor necrosis factor receptor
    A tumor necrosis factor receptor , or death receptor, is a trimeric cytokine receptor that binds tumor necrosis factors . The receptor cooperates with an adaptor protein , which is important in determining the outcome of the response A tumor necrosis factor receptor (TNFR), or death receptor, is a...

     (TNFRSF13B) deficiency, BAFF receptor
    B-cell activating factor
    B-cell activating factor also known as tumor necrosis factor ligand superfamily member 13B is a protein that in humans is encoded by the TNFLSF13B gene...

     deficiency.
  3. Normal numbers of B cells with decreased IgG and IgA
    IGA
    Iga or IGA may stand for:-Given name:* a female given name of Polish origin. The name originates from the female given name Jadwiga and stands for gia,or gina in the USA....

     and increased IgM
    IGM
    IGM as an acronym or abbreviation can refer to:* Immunoglobulin M , the primary antibody against A and B antigens on red blood cells* International Grandmaster, a chess ranking* intergalactic medium* Intragroup medium - see: Intracluster medium...

    : Hyper-IgM syndromes
  4. Normal numbers of B cells with isotype or light chain deficiencies: heavy chain
    Heavy chain
    ]The immunoglobulin heavy chain is the large polypeptide subunit of an antibody .A typical antibody is composed of two immunoglobulin heavy chains and two Ig light chains. Several different types of heavy chain exist that define the class or isotype of an antibody. These heavy chain types vary...

     deletions, kappa chain
    Immunoglobulin light chain
    ]The immunoglobulin light chain is the small polypeptide subunit of an antibody .A typical antibody is composed of two immunoglobulin heavy chains and two Ig light chains.-In humans:...

     deficiency, isolated IgG subclass deficiency, IgA with IgG subsclass deficiency, selective immunoglobulin A deficiency
    Selective immunoglobulin A deficiency
    Selective immunoglobulin A deficiency is a relatively mild genetic immunodeficiency. People with this deficiency lack immunoglobulin A , a type of antibody that protects against infections of the mucous membranes lining the mouth, airways, and digestive tract. It is defined as an undetectable...

  5. Specific antibody deficiency to specific antigens with normal B cell and normal Ig concentrations
  6. Transient hypogammaglobulinemia of infancy
    Transient hypogammaglobulinemia of infancy
    Transient hypogammaglobulinemia of infancy is a form of hypogammaglobulinemia appearing after birth, leading to a reduction in the level of IgG, and also sometimes IgA and IgM...

     (THI)

Secondary

Secondary (or acquired) forms of humoral immune deficiency are mainly:
  • Multiple myeloma
    Multiple myeloma
    Multiple myeloma , also known as plasma cell myeloma or Kahler's disease , is a cancer of plasma cells, a type of white blood cell normally responsible for the production of antibodies...

  • Chronic lymphoid leukemia
  • AIDS
    AIDS
    Acquired immune deficiency syndrome or acquired immunodeficiency syndrome is a disease of the human immune system caused by the human immunodeficiency virus...


Presentation and complications

The signs and symptoms of humoral immune deficiency depend on the cause, but generally include signs of hypogammaglobulinemia
Hypogammaglobulinemia
Hypogammaglobulinemia is a type of immune disorder characterized by a reduction in all types of gamma globulins.Hypogammaglobulinemia is a characteristic of common variable immunodeficiency.-Terminology:...

 (decrease of one or more types of antibodies) with presentations including repeated mild respiratory infections, and/or agammaglobulinemia (lack of all or most antibody production) which results in frequent severe infections and is often fatal.
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