Gamma globulin

Last updated
Schematic representation of a protein electrophoresis gel Electrophoresis.png
Schematic representation of a protein electrophoresis gel

Gamma globulins are a class of globulins, identified by their position after serum protein electrophoresis. [1] [2] The most significant gamma globulins are immunoglobulins (antibodies), although some immunoglobulins are not gamma globulins, and some gamma globulins are not immunoglobulins.

Contents

Use as medical treatment

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 having been exposed to hepatitis A or measles, or to make a kidney donor and a recipient compatible regardless of blood type or tissue match. Injections are also used to boost immunity in patients unable to 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practice than they were previously, and injections of gamma globulin previously recommended for travelers have largely been replaced by the use of hepatitis A vaccine.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 some 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. It appears that gamma globulin causes the spleen to ignore the antibody-tagged platelets, thus allowing them to survive and function.

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

Intravenous immunoglobulin (IVIG) may be used in Kawasaki disease.

In 1953, gamma globulin was shown to prevent paralytic polio. [3]

Being a product derived from bone marrow and lymph gland cells, gamma globulin injections, along with blood transfusions and intravenous drug use, can pass hepatitis C to their recipients. Once hepatitis C was identified in 1989, blood banks began screening all blood donors for the presence of the virus in their bloodstream. However, since hepatitis C is known to have been present since at least the 1940s, a gamma globulin shot received prior to the early 1990s put the recipient at risk of being infected.

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 with a different blood type (ABO-incompatible), or who is an unacceptable tissue match. Stanley Jordan at Cedars-Sinai Medical Center in Los Angeles pioneered this treatment. [4]

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).

Brutton's agammaglobulinemia is an X-linked recessive disorder characterized by recurrent infections in the early-post natal period attributable to failure of pre-B cells to mature. Unless treated with Intravenous Immunoglobulins, patients often die.

Related Research Articles

<span class="mw-page-title-main">Blood transfusion</span> Intravenous transference of blood products

Blood transfusion is the process of transferring blood products into a person's circulation intravenously. Transfusions are used for various medical conditions to replace lost components of the blood. Early transfusions used whole blood, but modern medical practice commonly uses only components of the blood, such as red blood cells, white blood cells, plasma, platelets, and other clotting factors.

<span class="mw-page-title-main">Serum protein electrophoresis</span> Laboratory test

Serum protein electrophoresis is a laboratory test that examines specific proteins in the blood called globulins. The most common indications for a serum protein electrophoresis test are to diagnose or monitor multiple myeloma, a monoclonal gammopathy of uncertain significance (MGUS), or further investigate a discrepancy between a low albumin and a relatively high total protein. Unexplained bone pain, anemia, proteinuria, chronic kidney disease, and hypercalcemia are also signs of multiple myeloma, and indications for SPE. Blood must first be collected, usually into an airtight vial or syringe. Electrophoresis is a laboratory technique in which the blood serum is applied to either an acetate membrane soaked in a liquid buffer, or to a buffered agarose gel matrix, or into liquid in a capillary tube, and exposed to an electric current to separate the serum protein components into five major fractions by size and electrical charge: serum albumin, alpha-1 globulins, alpha-2 globulins, beta 1 and 2 globulins, and gamma globulins.

<span class="mw-page-title-main">Multiple myeloma</span> Cancer of plasma cells

Multiple myeloma (MM), also known as plasma cell myeloma and simply myeloma, is a cancer of plasma cells, a type of white blood cell that normally produces antibodies. Often, no symptoms are noticed initially. As it progresses, bone pain, anemia, kidney dysfunction, and infections may occur. Complications may include hypercalcemia and amyloidosis.

The globulins are a family of globular proteins that have higher molecular weights than albumins and are insoluble in pure water but dissolve in dilute salt solutions. Some globulins are produced in the liver, while others are made by the immune system. Globulins, albumins, and fibrinogen are the major blood proteins. The normal concentration of globulins in human blood is about 2.6-3.5 g/dL.

Immunodeficiency, also known as immunocompromisation, 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 affect the patient's immune system. Examples of these extrinsic factors include HIV infection and environmental factors, such as nutrition. Immunocompromisation may also be due to genetic diseases/flaws such as SCID.

This is a list of AIDS-related topics, many of which were originally taken from the public domain U.S. Department of Health Glossary of HIV/AIDS-Related Terms, 4th Edition.

The direct and indirect Coombs tests, also known as antiglobulin test (AGT), are blood tests used in immunohematology. The direct Coombs test detects antibodies that are stuck to the surface of the red blood cells. Since these antibodies sometimes destroy red blood cells they can cause anemia; this test can help clarify the condition. The indirect Coombs test detects antibodies that are floating freely in the blood. These antibodies could act against certain red blood cells; the test can be carried out to diagnose reactions to a blood transfusion.

<span class="mw-page-title-main">Cryoglobulinemia</span> Medical condition

Cryoglobulinemia is a medical condition in which the blood contains large amounts of pathological cold sensitive antibodies called cryoglobulins – proteins that become insoluble at reduced temperatures. This should be contrasted with cold agglutinins, which cause agglutination of red blood cells.

<span class="mw-page-title-main">X-linked agammaglobulinemia</span> Medical condition

X-linked agammaglobulinemia (XLA) is a rare genetic disorder discovered in 1952 that affects the body's ability to fight infection. As the form of agammaglobulinemia that is X-linked, it is much more common in males. In people with XLA, the white blood cell formation process does not generate mature B cells, which manifests as a complete or near-complete lack of proteins called gamma globulins, including antibodies, in their bloodstream. B cells are part of the immune system and normally manufacture antibodies, which defend the body from infections by sustaining a humoral immunity response. Patients with untreated XLA are prone to develop serious and even fatal infections. A mutation occurs at the Bruton's tyrosine kinase (Btk) gene that leads to a severe block in B cell development and a reduced immunoglobulin production in the serum. Btk is particularly responsible for mediating B cell development and maturation through a signaling effect on the B cell receptor BCR. Patients typically present in early childhood with recurrent infections, in particular with extracellular, encapsulated bacteria. XLA is deemed to have a relatively low incidence of disease, with an occurrence rate of approximately 1 in 200,000 live births and a frequency of about 1 in 100,000 male newborns. It has no ethnic predisposition. XLA is treated by infusion of human antibody. Treatment with pooled gamma globulin cannot restore a functional population of B cells, but it is sufficient to reduce the severity and number of infections due to the passive immunity granted by the exogenous antibodies.

Hypogammaglobulinemia is an immune system disorder in which not enough gamma globulins are produced in the blood. This results in a lower antibody count, which impairs the immune system, increasing risk of infection. Hypogammaglobulinemia may result from a variety of primary genetic immune system defects, such as common variable immunodeficiency, or it may be caused by secondary effects such as medication, blood cancer, or poor nutrition, or loss of gamma globulins in urine, as in nonselective glomerular proteinuria. Patients with hypogammaglobulinemia have reduced immune function; important considerations include avoiding use of live vaccines, and take precautionary measures when traveling to regions with endemic disease or poor sanitation such as receiving immunizations, taking antibiotics abroad, drinking only safe or boiled water, arranging appropriate medical cover in advance of travel, and ensuring continuation of any immunoglobulin infusions needed.

<span class="mw-page-title-main">Monoclonal gammopathy</span> Excess myeloma protein or monoclonal gamma globulin in the blood

Monoclonal gammopathy, also known as paraproteinemia, is the presence of excessive amounts of myeloma protein or monoclonal gamma globulin in the blood. It is usually due to an underlying immunoproliferative disorder or hematologic neoplasms, especially multiple myeloma. It is sometimes considered equivalent to plasma cell dyscrasia. The most common form of the disease is monoclonal gammopathy of undetermined significance.

Rho(D) immune globulin (RhIG) is a medication used to prevent RhD isoimmunization in mothers who are RhD negative and to treat idiopathic thrombocytopenic purpura (ITP) in people who are Rh positive. It is often given both during and following pregnancy. It may also be used when RhD-negative people are given RhD-positive blood. It is given by injection into muscle or a vein. A single dose lasts 12 weeks. It is made from human blood plasma.

Primary immunodeficiencies are disorders in which part of the body's immune system is missing or does not function normally. To be considered a primary immunodeficiency (PID), the immune deficiency must be inborn, not caused by secondary factors such as other disease, drug treatment, or environmental exposure to toxins. Most primary immunodeficiencies are genetic disorders; the majority are diagnosed in children under the age of one, although milder forms may not be recognized until adulthood. While there are over 430 recognized inborn errors of immunity (IEIs) as of 2019, the vast majority of which are PIDs, most are very rare. About 1 in 500 people in the United States are born with a primary immunodeficiency. Immune deficiencies can result in persistent or recurring infections, auto-inflammatory disorders, tumors, and disorders of various organs. There are currently limited treatments available for these conditions; most are specific to a particular type of PID. Research is currently evaluating the use of stem cell transplants (HSCT) and experimental gene therapies as avenues for treatment in limited subsets of PIDs.

In immunology, passive immunity is the transfer of active humoral immunity of ready-made antibodies. Passive immunity can occur naturally, when maternal antibodies are transferred to the fetus through the placenta, and it can also be induced artificially, when high levels of antibodies specific to a pathogen or toxin are transferred to non-immune persons through blood products that contain antibodies, such as in immunoglobulin therapy or antiserum therapy. Passive immunization is used when there is a high risk of infection and insufficient time for the body to develop its own immune response, or to reduce the symptoms of ongoing or immunosuppressive diseases. Passive immunization can be provided when people cannot synthesize antibodies, and when they have been exposed to a disease that they do not have immunity against.

Hepatitis B immunoglobulin (HBIG) is a human immunoglobulin that is used to prevent the development of hepatitis B and is used for the treatment of acute exposure to HBsAg.

Hans Dieter Ochs, is an immunologist and pediatrician. He is Professor of Pediatrics, Division of Immunology, Department of Pediatrics, University of Washington School of Medicine, Seattle.

Gestational (incidental) thrombocytopenia is a condition that commonly affects pregnant women. Thrombocytopenia is defined as the drop in platelet count from the normal range of 150,000–400,000/μL to a count lower than 150,000/μL. There is still ongoing research to determine the reason for the lowering of platelet count in women with a normal pregnancy. Some researchers speculate the cause to be dependent on dilution, decreased production of platelets, or an increased turnover event. Although women with normal pregnancy experience a low platelet count, women experiencing a continuous drop in platelet will be diagnosed with thrombocytopenia and women with levels greater than 70,000/μL will be diagnosed with gestational thrombocytopenia.

VZV globulin or VZV antibodies is an immune system medication that is used mostly for immunosuppressed patients who have been or may be exposed to the varicella zoster virus. It shortens the course of cutaneous disease and may protect against its dissemination. Varicella zoster virus is a human herpes virus that causes chickenpox, shingles, Ramsay Hunt syndrome type II, and postherpetic neuralgia. Unlike a Zoster vaccine which provides durable immunity, the protection is passive and short term; it may need to be readministered every 2-4 weeks as necessary. This medication is not recommended for administration to immune-competent persons for the treatment of active disease.

Vaccinia immune globulin (VIG) is made from the pooled blood of individuals who have been inoculated with the smallpox vaccine. The antibodies these individuals developed in response to the smallpox vaccine are removed and purified. This results in VIG. It can be administered intravenously. It is used to treat individuals who have developed progressive vaccinia after smallpox vaccination.

Immunoglobulin therapy is the use of a mixture of antibodies to treat several health conditions. These conditions include primary immunodeficiency, immune thrombocytopenic purpura, chronic inflammatory demyelinating polyneuropathy, Kawasaki disease, certain cases of HIV/AIDS and measles, Guillain-Barré syndrome, and certain other infections when a more specific immunoglobulin is not available. Depending on the formulation it can be given by injection into muscle, a vein, or under the skin. The effects last a few weeks.

References

  1. S. Ramakrishnan (October 2004). Textbook of Medical Biochemistry. Orient Blackswan. pp. 157–. ISBN   978-81-250-2071-4.
  2. Allan Gaw; Michael Murphy; Rajeev Srivastava, Robert A. Cowan, Denis St. J. O'Reilly (7 June 2013). Clinical Biochemistry E-Book: An Illustrated Colour Text. Elsevier Health Sciences. pp. 52–. ISBN   978-0-7020-5414-3.{{cite book}}: CS1 maint: multiple names: authors list (link)
  3. Hammon WM, Coriell LL, Wehrle PF, Stokes J (1953). "Evaluation of Red Cross gamma globulin as a prophylactic agent for poliomyelitis. IV. Final report of results based on clinical diagnoses". Journal of the American Medical Association. 151 (15): 1272–85. PMID   13034471.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  4. "Multi-center Study Finds Therapy Boosts Kidney Transplants In 'Highly Sensitized' Patients". Science Daily. December 8, 2004.