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Polyclonal gammopathy, gammopathy, gamma globulin, persistent polyclonal b-cell lymphocytosis, lymphocytic interstitial pneumonia, benign hyperg [...]




GAMMOPATHY

Gamma globulin



GAMMA GLOBULIN


Gamma globulins are a class of proteins in the blood, identified by their position after serum protein electrophoresis. The most significant gamma globulins are immunoglobulins ( Igs ), more commonly known as antibodies, although some Igs are not gamma globulins, and some gamma globulins are not Igs.

Injections

Gamma globulin injections are usually given in an attempt to temporarily boost a patient's immunity against disease. Injections are most commonly used on patients who have been exposed to hepatitis A or measles, or to make a kidney donor and recipient compatible regardless of blood type of tissue match. Injections are also used to boost immunity in patients who cannot produce gamma globulins naturally because of an immune deficiency, such as X-linked agammaglobulinemia and hyper IgM syndrome. Such injections are less common in modern medical practice than they were previously, and injections of gamma globulin previously recommended for travelers have largely been replaced by the use of hepatitis A vaccine.

Gamma globulin infusions are also used to treat immunological diseases, such as idiopathic thrombocytopenia purpura (ITP), a disease in which the platelets are being attacked by antibodies, leading to seriously low platelet counts. Gamma globulin apparently causes the spleen to ignore the antibody-tagged platelets, thus allowing them to survive and function.

A recent clinical trial of gamma globulin in Chronic Fatigue Syndrome patients had no recognizable benefit, while an older trial showed improvement. The success of this treatment remains uncertain.

Another theory on how gamma globulin administration works in autoimmune disease is by overloading the mechanisms which degrade gamma globulins. Overloading the degradation mechanism causes the harmful gamma globulins to have a much shorter halflife in sera.

Pathology

An excess is known as hypergammaglobulinemia. A deficiency is known as hypogammaglobulinemia.

A disease of gamma globulins is called a gammopathy (for example, in monoclonal gammopathy of undetermined significance.)

Disease treatments

Kawasaki disease
Kidney Transplant: Intravenous Gamma globulin was FDA approved in 2004 to reduce antibodies in a patient with kidney failure to allow that person to accept a kidney from a donor who has a different blood type, (ABO incompatible) or is an unacceptable tissue match. Dr. Stanley Jordan at Cedars-Sinai Medical Center in Los Angeles pioneered this treatment.

External links

http://www.sciencedaily.com/releases/2004/12/041208234532.htm



PERSISTENT POLYCLONAL B-CELL LYMPHOCYTOSIS


Persistent polyclonal B-cell lymphocytosis (PPBL) is very rare anomaly of the human immune system characterized by mild leukocytosis, chronic stable absolute polyclonal b-cell lymphocytosis, elevated polyclonal IgM and binucleated cells. Ten percent of patients present with splenomegaly and lymphadenopathy. Some patients report a varying degree of fatigue, consistent with a chronic fatigue syndrome, Although cases of non-smoking women or men have been reported, patients are predominantly young smoking women.

Molecular and immunological analysis

Genetically PPBL has been associated with HLA-DR7 (which is normally present in 26% in the caucasian population). Chromosome analysis has detected an Isochromosome +i(3q) with or without premature chromosome condensation. Also a t(14;18)(q22;21) bcl-2/IgH rearrangement has been described, as usually seen in follicular lymphoma. Immunologically peripheral B-cells showed an expansion of functional IgD+ positive CD 27 cells.

Prognosis

In the followup of 111 patients, most remained stable and event free. However, two patients developed IgM gammopathy 2 lung cancer; one developed cervical cancer and three developed non-Hodgkin-Lymphoma. The possibility of developing a clonal proliferation, malignant lymphoma or secondary solid cancer led the authors to conclude not to classify PPBL as a benign pathology, as has been previously postulated but rather to recommend a careful and continued clinical and biological longterm follow-up.

References



LYMPHOCYTIC INTERSTITIAL PNEUMONIA

Lymphocytic interstitial pneumonia (also called lymphocytic interstitial pneumonitis or LIP) is a syndrome secondary to autoimmune and other lymphoproliferative disorders. Symptoms include fever, cough, and shortness of breath. Lymphocytic interstitial pneumonia applies to a disorders associated with both, monoclonal or polyclonal gammopathy.

Symptoms

In patients with lymphocytic interstitial pneumonia, these patients may present with lymphadenopathy, enlarged liver, enlarged spleen, enlarged salivary gland, thickening and widening of the extremities of the fingers and toes, and breathing symptoms such as shortness of breath and wheezing.

Diagnosis

Arterial blood gases may reveal hypoxemia when tested in a lab. Respiratory alkalosis may also be present.

Causes

Possible causes of lymphocytic interstitial pneumonia include the Epstein-Barr virus and Human Immunodeficiency Virus.

Treatment

Patients presenting with no symptoms, and not affected by the syndrome may not require treatment. However, antibiotics are usually required for bacterial pulmonary infections. Bronchodilators may assist with breathing issues and resolution may occur with the use of Highly Active Anti-Retroviral Therapy. However, responses to different treatments are widely varied, and no single first line treatment represents the default treatment for lymphocytic interstitial pneumonia.

References

Pneumonia



HYPERGAMMAGLOBULINEMIA


Hypergammaglobulinemia is a medical condition with elevated levels of gamma globulin.

It is a type of immunoproliferative disorder.

Types

Hypergammaglobulinemia is a condition that is characterized by the increased levels of a certain immunoglobulin in the blood serum. The name of the disorder refers to the position of the excess of proteins after serum protein electrophoresis (found in the gammaglobulin region).

Most hypergammaglobulinemias are caused by an excess of immunoglobulin M (IgM), because this is the default immunoglobulin type prior to class switching. Some types or hypergammaglobulinemia are actually caused by a deficiency in the other major types of immunoglobulins, which are IgA, IgE and IgG.

There are 5 types of hypergammaglobulinemias associated with hyper IgM.

It should be noted that MeSH considers hyper IgM syndrome to be a form of dysgammaglobulinemia, not a form of hypergammaglobulinemia .

Type 1

X-linked immunodeficiency with hyper-immunoglobulin M, which is also called type 1 hyper IgM, is a rare form of primary immunodeficiency disease caused by a mutation in the Tumor Necrosis Factor Super Family member 5 (TNFSF5) gene, which codes for CD40 ligand. This gene is located on the long arm of the X chromosome at position 26, denoted Xq26. The mutation in the TNFSF5 gene causes there to be no recognition of CD40 by CD40 ligand, and thus the T cells do not induce Ig class switching in B cells, so there are markedly reduced levels of IgG, IgA, and IgE, but have normal or elevated levels of IgM. CD40 ligand is also required in the functional maturation of T lymphocytes and macrophages, so patients with this disorder have a variable defect in T-lymphocyte and macrophage effector function, as well as hyper IgM.

Type 2

Immunodeficiency with hyper IgM type 2 is caused by a mutation in the Activation-Induced Cysteine Deaminase (AICDA) gene, which is located on the short arm of chromosome 12. The protein that is encoded by this gene is called Activation-Induced Cytidine Deaminase (AICDA) and functions as a DNA-editing deaminase that induces somatic hypermutation, class switch recombination, and immunoglobulin gene conversion in B cells. When a person is homozygous for the mutation in the AICDA gene, the protein fails to function, and thus somatic hypermutation, class switch recombination, and immunoglobulin gene conversion cannot occur, which creates an excess of IgM.

Type 3

Immunodeficiency with hyper IgM type 3 is caused by a mutation in the gene that codes for CD40. As mentioned above, CD40 is expressed on the surface of B cells, and its binding to CD40 ligand on activated T cells induces Ig class switching. When the mutation is present, there is no signal for B cells to undergo class switching, so there is an excess of IgM and little to no other immunoglobulin types produced.

Type 4

Immunodeficiency with hyper IgM type 4 is poorly characterized. All that is known is that there is an excess of IgM in the blood, with normal levels of the other immunoglobulins. The exact cause is yet to be determine.

Type 5

Immunodeficiency with hyper IgM type 5 is caused by a mutation in the Uracil DNA Glycosylase (UNG) gene, which, like AICDA, is located on chromosome 12. This codes for Uracil DNA Glycosylase, which is responsible for excising previous uracil bases that are due to cytosine deamination, or previous uracil misincorporation from double-stranded previous DNA substrates. This enzyme is also responsible for helping with gene conversion during somatic recombination in B cells. The mutation in the gene causes an enzyme that does not function properly, thus gene conversion does not proceed and class switching cannot occur.

See also

Monoclonal gammopathy of undetermined significance

References



LYMPHOPROLIFERATIVE DISORDERS


Lymphoproliferative disorders (LPDs) refer to several conditions in which lymphocytes are produced in excessive quantities. They typically occur in patients who have compromised immune systems. They are sometimes equated with immunoproliferative disorders, but technically Lymphoproliferative disorders are a subset of immunoproliferative disorders, along with hypergammaglobulinemia and paraproteinemias.

Examples of LPDs

follicular lymphoma
chronic lymphocytic leukemia
acute lymphoblastic leukemia
hairy cell leukemia
lymphomas
multiple myeloma
Waldenstrom's_macroglobulinemia
Wiskott-Aldrich syndrome
post-transplant lymphoproliferative disorder
Autoimmune lymphoproliferative syndrome (ALPS)
Lymphoid interstitial pneumonia

Types

Lymphoproliferative disorders are a set of disorders characterized by the abnormal proliferation of lymphocytes into a monoclonal lymphocytosis. The two major types of lymphocytes are B cells and T cells, which are derived from pluripotent hematopoetic stem cells in the bone marrow. Individuals who have some sort of immunodysfuction are susceptible to developing a lymphoproliferative disorder because when any of the numerous control points of the immune system become dysfunctional, immunodeficiency or deregulation of lymphocytes is more likely to occur. There are several inherited gene gene mutations that have been identified to cause lymphoproliferative disorders, however there are also acquired and iatrogenic causes.

X-linked Lymphoproliferative disorder


There is a mutation on the X chromosome that has been found to be associated with a T cell and NK cell lymphoproliferative disorder.

Autosomal lymphoproliferative disorder


Some children with autoimmune lymphoproliferative disorders are heterozygous for a mutation in the gene that codes for the Fas receptor. Which is located on the long arm of chromosome 10 at position 24.1, denoted 10q24.1. This gene is member 6 of the TNF-receptor superfamily (TNFRSF6). The Fas receptor contains a death domain and has been shown to play a central role in the physiological regulation of programmed cell death. Normally, stimulation of recently activated T cells by antigen leads to coexpression of Fas and Fas receptor on the T cell surface. The engagement of Fas by Fas receptor results in apoptosis of the cell and is important for eliminating T cells that are repeatedly stimulated by antigens. As a result of the mutation in the Fas receptor gene, there is no recognition of Fas by Fas receptor, leading to a primitive population of T cells that proliferates in an uncontrolled manner.

Other inherited causes

Boys with X-linked immunodeficiency syndrome are at a higher risk of mortality associated with Epstein-Barr Virus infections, and are predisposed to develop a lymphoproliferative disorder or lymphoma.

Children with common variable immune deficiency (CVID) are also at a higher risk of developing a lymphoproliferative disorder.

Some disorders that predispose a person to lymphoproliferative disorders are severe combined immuno deficiency (SCID), Chédiak-Higashi syndrome, Wiskott-Aldrich syndrome (an X-linked recessive disorder) and Ataxia telangiectasia.

Interestingly, even though Ataxia telangiectasia is an autosomal recessive disorder, people who are heterozygotes for this still have an increased risk of developing a lymphoproliferative disorder.

Acquired causes

Viral infection is a very common cause of lymphoproliferative disorders. The most common is congenital HIV infection because it is highly associated with acquired immunodeficiency, which often leads to lymphoproliferative disorders.

Iatrogenic causes

There are many lymphoproliferative disorders that are associated with organ transplantation and immunosuppressant therapies. In most reported cases, these cause B cell lymphoproliferative disorders, however some T cell variations have been described. The T cell variations are usually caused by the prolonged use of T cell suppressant drugs, such as sirolimus, tacrolimus or cyclosporine A.

See also

Evans syndrome
Leukaemia
Lymphoma
Lymphocytosis
Myeloma
Myeloproliferative disease

References

External links

Sloan-Kettering



IMMUNOPROLIFERATIVE DISORDER


Immunoproliferative disorders (also known as “immunoproliferative diseases” or “immunoproliferative neoplasms”) are disorders of the immune system that are characterized by the abnormal proliferation of the primary cells of the immune system, which includes B cells, T cells and Natural killer (NK) cells, or by the excessive production of immunoglobulins (also known as antibodies).

Classes

These disorders are subdivided into three main classes, which are lymphoproliferative disorders, hypergammaglobulinemia, and paraproteinemia. The first is cellular, and the other two are humoral (however, humoral excess can be secondary to cellular excess.)

Lymphoproliferative disorders (LPDs) refer to several conditions in which lymphocytes are produced in excessive quantities. They typically occur in patients who have compromised immune systems. This subset is sometimes incorrectly equated with immunoproliferative disorders .

Humoral
Hypergammaglobulinemia is characterized by increased levels of immunoglobulins in the blood serum. Five different hypergammaglobulinemias are caused by an excess of immunoglobulin M (IgM), and some types are caused by a deficiency in the other major types of immunoglobulins.
Paraproteinemia or monoclonal gammopathy is the presence of excessive amounts of a single monoclonal gammaglobulin (called a paraprotein ) in the blood.

References

See also

Myeloproliferative disease

External links

immunoproliferative enteropathy
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