Immunoglobulin deficiency syndromes

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Definition

Immunoglobulin deficiency syndromes are a group of immunodeficiency

disorders in which the patient has reduced number of or lack of

antibodies.

(Immunodeficiency Definition)

Immunodeficiency disorders are a group of disorders in which part of

the immune system is missing or defective. Therefore, the body's

ability to fight infections is impaired. As a result, the person with

an immunodeficiency disorder will have frequent infections that are

generally more severe and last longer than usual.

Description

The immune system is the body's main system to fight infections. Any

defect in the immune system decreases a person's ability to fight

infections. A person with an immunodeficiency disorder may get more

frequent infections, heal more slowly, and have a higher incidence of

some cancers.

The normal immune system involves a complex interaction of certain

types of cells that can recognize and attack " foreign " invaders, such

as bacteria, viruses, and fungi. It also plays a role in fighting

cancer. The immune system has both innate and adaptive components.

Innate immunity is made up of immune protections people are born

with. Adaptive immunity develops throughout life. It adapts to fight

off specific invading organisms. Adaptive immunity is divided into

two components: humoral immunity and cellular immunity.

The innate immune system is made up of the skin (which acts as a

barrier to prevent organisms from entering the body), white blood

cells called phagocytes, a system of proteins called the complement

system, and chemicals called interferon. When phagocytes encounter an

invading organism, they surround and engulf it to destroy it. The

complement system also attacks bacteria. The elements in the

complement system create a hole in the outer layer of the target

cell, which leads to the death of the cell.

The adaptive component of the immune system is extremely complex, and

is still not entirely understood. Basically, it has the ability to

recognize an organism or tumor cell as not being a normal part of the

body, and to develop a response to attempt to eliminate it.

The humoral response of adaptive immunity involves a type of cell

called B lymphocytes. B lymphocytes manufacture proteins called

antibodies (which are also called immunoglobulins). Antibodies attach

themselves to the invading foreign substance. This allows the

phagocytes to begin engulfing and destroying the organism. The action

of antibodies also activates the complement system. The humoral

response is particularly useful for attacking bacteria.

The cellular response of adaptive immunity is useful for attacking

viruses, some parasites, and possibly cancer cells. The main type of

cell in the cellular response is T lymphocytes. There are helper T

lymphocytes and killer T lymphocytes. The helper T lymphocytes play a

role in recognizing invading organisms, and they also help killer T

lymphocytes to multiply. As the name suggests, killer T lymphocytes

act to destroy the target organism.

Defects can occur in any component of the immune system or in more

than one component (combined immunodeficiency). Different

immunodeficiency diseases involve different components of the immune

system. The defects can be inherited and/or present at birth

(congenital) or acquired.

Congenital immunodeficiency disorders

Congenital immunodeficiency is present at the time of birth, and is

the result of genetic defects. Even though more than 70 different

types of congenital immunodeficiency disorders have been identified,

they rarely occur. Congenital immunodeficiencies may occur as a

result of defects in B lymphocytes, T lymphocytes, or both. They can

also occur in the innate immune system.

B lymphocyte deficiency

If there is an abnormality in either the development or function of B

lymphocytes, the ability to make antibodies will be impaired. This

allows the body to be susceptible to recurrent infections.

Bruton's agammaglobulinemia, also known as X-linked

agammaglobulinemia, is one of the most common congenital

immunodeficiency disorders. The defect results in a decrease or

absence of B lymphocytes, and therefore a decreased ability to make

antibodies. People with this disorder are particularly susceptible to

infections of the throat, skin, middle ear, and lungs. It is seen

only in males because it is caused by a genetic defect on the X

chromosome. Since males have only one X chromosome, they always have

the defect if the gene is present. Females can have the defective

gene, but since they have two X chromosomes, there will be a normal

gene on the other X chromosome to counter it. Women may pass the

defective gene on to their male children.

Another type of B lymphocyte deficiency involves a group of disorders

called selective immunoglobulin deficiency syndomes. Immunoglobulin

is another name for antibody, and there are five different types of

immunoglobulins (called IgA, IgG, IgM, IgD, and IgE). The most common

type of immunoglobulin deficiency is selective IgA deficiency. The

amounts of the other antibody types are normal. Some patients with

selective IgA deficiency experience no symptoms, while others have

occasional lung infections and diarrhea. In another immunoglobulin

disorder, IgG and IgA antibodies are deficient and there is increased

IgM. People with this disorder tend to get severe bacterial

infections.

Common variable immunodeficiency is another type of B lymphocyte

deficiency. In this disorder, the production of one or more of the

immunoglobulin types is decreased and the antibody response to

infections is impaired. It generally develops around the age of 10-

20. The symptoms vary among affected people. Most people with this

disorder have frequent infections, and some will also experience

anemia and rheumatoid arthritis. Many people with common variable

immunodeficiency develop cancer.

T lymphocyte deficiencies

Severe defects in the ability of T lymphocytes to mature results in

impaired immune responses to infections with viruses, fungi, and

certain types of bacteria. These infections are usually severe and

can be fatal.

Di syndrome is a T lymphocyte deficiency that starts during

fetal development, but it isn't inherited. Children with Di

syndrome either do not have a thymus or have an underdeveloped

thymus. Since the thymus is a major organ that directs the production

of T-lymphocytes, these patients have very low numbers of T-

lymphocytes. They are susceptible to recurrent infections, and

usually have physical abnormalities as well. For example, they may

have low-set ears, a small receding jawbone, and wide-spaced eyes.

In some cases, no treatment is required for Di syndrome because

T lymphocyte production improves. Either an underdeveloped thymus

begins to produce more T lymphocytes or organ sites other than the

thymus compensate by producing more T lymphocytes.

Combined immunodeficiencies

Some types of immunodeficiency disorders affect both B lymphocytes

and T lymphocytes. For example, severe combined immunodeficiency

disease (SCID) is caused by the defective development or function of

these two types of lymphocytes. It results in impaired humoral and

cellular immune responses. SCID is usually recognized during the

first year of life. It tends to cause a fungal infection of the mouth

(thrush), diarrhea, failure to thrive, and serious infections. If not

treated with a bone marrow transplant, a person with SCID will

generally die from infections before age two.

Disorders of innate immunity

Disorders of innate immunity affect phagocytes or the complement

system. These disorders also result in recurrent infections.

Acquired immunodeficiency disorders

Acquired immunodeficiency is more common than congenital

immunodeficiency. It is the result of an infectious process or other

disease. For example, the human immunodeficiency virus (HIV) is the

virus that causes acquired immunodeficiency syndrome (AIDS). However,

this is not the most common cause of acquired immunodeficiency.

Acquired immunodeficiency often occurs as a complication of other

conditions and diseases. For example, the most common causes of

acquired immunodeficiency are malnutrition, some types of cancer, and

infections. People who weigh less than 70% of the average weight of

persons of the same age and gender are considered to be malnourished.

Examples of types of infections that can lead to immunodeficiency are

chickenpox, cytomegalovirus, German measles, measles, tuberculosis,

infectious mononucleosis (Epstein-Barr virus), chronic hepatitis,

lupus, and bacterial and fungal infections.

Sometimes, acquired immunodeficiency is brought on by drugs used to

treat another condition. For example, patients who have an organ

transplant are given drugs to suppress the immune system so the body

will not reject the organ. Also, some chemotherapy drugs, which are

given to treat cancer, have the side effect of killing cells of the

immune system. During the period of time that these drugs are being

taken, the risk of infection increases. It usually returns to normal

after the person stops taking the drugs.

Causes & symptoms

Congenital immunodeficiency is caused by genetic defects, and they

generally occur while the fetus is developing in the womb. These

defects affect the development and/or function of one or more of the

components of the immune system. Acquired immunodeficiency is the

result of a disease process, and it occurs later in life. The causes,

as described above, can be diseases, infections, or the side effects

of drugs given to treat other conditions.

People with an immunodeficiency disorder tend to become infected by

organisms that don't usually cause disease in healthy persons. The

major symptoms of most immunodeficiency disorders are repeated

infections that heal slowly. These chronic infections cause symptoms

that persist for long periods of time. People with chronic infection

tend to be pale and thin. They may have skin rashes. Their lymph

nodes tend to be larger than normal and their liver and spleen may

also be enlarged. The lymph nodes are small organs that house

antibodies and lymphocytes. Broken blood vessels, especially near the

surface of the skin, may be seen. This can result in black-and-blue

marks in the skin. The person may loose hair from their head.

Sometimes, a red inflammation of the lining of the eye

(conjunctivitis) is present. They may have crusty appearance in and

on the nose from chronic nasal dripping.

Diagnosis

Usually, the first sign that a person might have an immunodeficiency

disorder is that they don't improve rapidly when given antibiotics to

treat an infection. Strong indicators that an immunodeficiency

disorder may be present is when rare diseases occur or the patient

gets ill from organisms that don't normally cause diseases,

especially if the patient gets repeatedly infected. If this happens

in very young children it is an indication that a genetic defect may

be causing an immunodeficiency disorder. When this situation occurs

in older children or young adults, their medical history will be

reviewed to determine if childhood diseases may have caused an

immunodeficiency disorder. Other possibilities will then be

considered, such as recently acquired infections--for example, HIV,

hepatitis, tuberculosis, etc.

Laboratory tests are used to determine the exact nature of the

immunodeficiency. Most tests are performed on blood samples. Blood

contains antibodies, lymphocytes, phagocytes, and complement

components; all of the major immune components that might cause

immunodeficiency. A blood cell count will determine if the number of

phagocytic cells or lymphocytes is below normal. Lower than normal

counts of either of these two cell types correlates with

immunodeficiencies. The blood cells are also checked for their

appearance. Sometimes a person may have normal cell counts, but the

cells are structurally defective. If the lymphocyte cell count is

low, further testing is usually done to determine whether any

particular type of lymphocyte is lower than normal. A lymphocyte

proliferation test is done to determine if the lymphocytes can

respond to stimuli. The failure to respond to stimulants correlates

with immunodeficiency. Antibody levels can be measured by a process

called electrophoresis. Complement levels can be determined by

immunodiagnostic tests.

Treatment

There is no cure for immunodeficiency disorders. Therapy is aimed at

controlling infections and, for some disorders, replacing defective

or absent components.

Patients with Bruton's agammaglobulinemia must be given periodic

injections of a substance called gamma globulin throughout their

lives to make up for their decreased ability to make antibodies. The

gamma globulin preparation contains antibodies against common

invading bacteria. If left untreated, the disease is usually fatal.

Common variable immunodeficiency also is treated with periodic

injections of gamma globulin throughout life. Additionally,

antibiotics are given when necessary to treat infections.

Patients with selective IgA deficiency usually do not require any

treatment. Antibiotics can be given for frequent infections.

In some cases, no treatment is required for Di syndrome because

T lymphocyte production improves on its own. Either an underdeveloped

thymus begins to produce more T lymphocytes or organ sites other than

the thymus compensate by producing more T lymphocytes. In some severe

cases, a bone marrow transplant or thymus transplant can be done to

correct the problem.

For patients with SCID, bone marrow transplantation is necessary. In

this procedure, healthy bone marrow from a donor who has a similar

type of tissue (usually a relative, like a brother or sister) is

removed. The bone marrow is a substance that resides in the cavity of

bones. It is the factory that produces blood, including some of the

white blood cells that make up the immune system. The bone marrow of

the person receiving the transplant is destroyed, and is then

replaced with marrow from the donor.

Treatment of the HIV infection that causes AIDS consists of drugs

called antivirals. These drugs attempt to inhibit the process that

the virus goes through to kill T lymphocytes. Several of these drugs

used in various combinations with one another can prolong the period

of time before the disease becomes apparent. However, this is not a

cure. Other treatments for people with AIDS are aimed at the

particular infections that arise as a result of the impaired immune

system.

In most cases, immunodeficiency caused by malnutrition is reversible.

The health of the immune system is directly linked to the nutritional

health of the patient. Among the essential nutrients required by the

immune system are proteins, vitamins, iron, and zinc.

For people being treated for cancer, periodic relief from

chemotherapy drugs can restore the function of the immune system.

In general, people with immunodeficiency disorders should maintain a

healthy diet. This is because malnutrition can aggravate

immunodeficiencies. They should also avoid being near people who have

colds or are sick because they can easily acquire new infections. For

the same reason, they should practice good personal hygiene,

especially dental care. People with immunodeficiency disorders should

also avoid eating undercooked food because it might contain bacteria

that could cause infection. This food would not cause infection in

normal persons, but in someone with an immunodeficiency, food is a

potential source of infectious organisms. People with

immunodeficiency should be given antibiotics at the first indication

of an infection.

Prognosis

The prognosis depends on the type of immunodeficiency disorder.

People with Bruton's agammaglobulinemia who are given injections of

gamma globulin generally live into their 30s or 40s. They often die

from chronic infections, usually of the lung. People with selective

IgA deficiency generally live normal lives. They may experience

problems if given a blood transfusion, and therefore they should wear

a Medic Alert bracelet or have some other way of alerting any

physician who treats them that they have this disorder.

SCID is the most serious of the immunodeficiency disorders. If a bone

marrow transplant is not successfully performed, the child usually

will not live beyond two years old.

People with HIV/AIDS are living longer than in the past because of

the antiviral drugs that became available in the mid 1990s. However,

AIDS is still a fatal disease. People with AIDS usually die of

opportunistic infections, which are infections that occur because the

impaired immune system is unable to fight them.

Prevention

There is no way to prevent a congenital immunodeficiency disorder.

However, someone with a congenital immunodeficiency disorder might

want to consider getting genetic counseling before having children to

find out if there is a chance they will pass the defect on to their

children.

Some of the infections associated with acquired immunodeficiency can

be prevented or treated before they cause problems. For example,

there are effective treatments for tuberculosis and most bacterial

and fungal infections. HIV infection can be prevented by

practicing " safe sex " and not using illegal intravenous drugs. These

are the primary routes of transmitting the virus. For people who

don't know the HIV status of the person with whom they are having

sex, safe sex involves using a condom.

Malnutrition can be prevented by getting adequate nutrition.

Malnutrition tends to be more of a problem in developing countries.

Terms:

Agammaglobulinemia

The lack of gamma globulins in the blood. Antibodies are the main

gamma globulins of interest, so this term means a lack of antibodies.

Immunoglobulin deficiency syndromes

Definition

Immunoglobulin deficiency syndromes are a group of immunodeficiency

disorders in which the patient has reduced number of or lack of

antibodies.

Description

Immunoglobulins (Ig) are antibodies. There are five major classes of

antibodies: IgG, IgM, IgA, IgD, and IgE.

IgG is the most abundant of the classes of immunoglobulins. It is the

antibody for viruses, bacteria, and antitoxins. It is found in most

tissues and plasma.

IgM is the first antibody present in an immune response.

IgA is an early antibody for bacteria and viruses. It is found in

saliva, tears, and all other mucous secreations.

IgD activity is unknown.

IgE is present in the respiratory secretions. It is an antibody for

parasitic diseases, Hodgkin's disease, hay fever, atopic dermatitis,

and allergic asthma).

All antibodies are made by B-lymphocytes (B-cells). Any disease that

harms the development or function of B-cells will cause a decrease in

the amount of antibodies produced. Since antibodies are essential in

fighting infectious diseases, people with immunoglobulin deficiency

syndromes become ill more often. However, the cellular immune system

is still functional, so these patients are more prone to infection

caused by organisms usually controlled by antibodies. Most of these

invading germs (microbes) make capsules, a mechanism used to confuse

the immune system. In a healthy body, antibodies can bind to the

capsule and overcome the bacteria's defenses. The bacteria that make

capsules include the streptococci, meningococci, and Haemophilus

influenzae. These organisms cause such diseases as otitis, sinusitis,

pneumonia, meningitis, osteomyelitis, septic arthritis, and sepsis.

Patients with immunoglobulin deficiencies are also prone to some

viral infections, including echovirus, enterovirus, and hepatitis B.

They may also have a bad reaction to the attenuated version of the

polio virus vaccine.

There are two types of immunodeficiency diseases: primary and

secondary. Secondary disorders occur in normally healthy bodies that

are suffering from an underlying disease. Once the disease is

treated, the immunodeficiency is reversed. Immunoglobulin deficiency

syndromes are primary immunodeficiency diseases, occurring because of

defective B-cells or antibodies. They account for 50% of all primary

immunodeficiencies, and they are, therefore, the most prevalent type

of immunodeficiency disorders.

X-linked agammaglobulinemia is an inherited disease. The defect is on

the X chromosome and, consequently, this disease is seen more

frequently in males than females. The defect results in a failure of

B-cells to mature. Mature B-cells are capable of making antibodies

and developing " memory, " a feature in which the B-cell will rapidly

recognize and respond to an infectious agent the next time it is

encountered. All classes of antibodies are decreased in

agammaglobulinemia.

Selective IgA deficiency is an inherited disease, resulting from a

failure of B-cells to switch from making IgM, the early antibody, to

IgA. Although the B-cell numbers are normal, and the B-cells are

otherwise normal (they can still make all other classes of

antibodies), the amount of IgA produced is limited. This results in

more infections of mucosal surfaces, such as the nose, throat, lungs,

and intestine.

Transient hypogammaglobulinemia of infancy is a temporary disease of

unknown cause. It is believed to be caused by a defect in the

development of T-helper cells (cells that recognize foreign antigens

and activate T- and B-cells in an immune response). As the child

ages, the number and condition of T-helper cells improves and this

situation corrects itself. Hypogammaglobulinemia is characterized by

low levels of gammaglobulin (antibodies) in the blood. During the

disease period, patients have decreased levels of IgG and IgA

antibodies. In lab tests, the antibodies that are present do not

react well with infectious bacteria.

Common variable immunodeficiency is a defect in both B cells and T-

lymphocytes. It results in a near complete lack of antibodies in the

blood.

Ig heavy chain deletions is a genetic disease in which part of the

antibody molecule isn't produced. It results in the loss of several

antibody classes and subclasses including most IgG antibodies and all

IgA and IgE antibodies. The disease occurs because part of the gene

for the heavy chain has been lost.

Selective IgG subclass deficiencies is a group of genetic diseases in

which some of the subclasses of IgG are not made. There are four

subclasses in the IgG class of antibodies. As the B-cell matures, it

can switch from one subclass to another. In these diseases there is a

defect in the maturation of the B-cells that results in a lack of

switching.

IgG deficiency with hyper-IgM is a disease that results when the B-

cell fails to switch from making IgM to IgG. This produces an

increase in the amount of IgM antibodies present and a decrease in

the amount of IgGaantibodies. This disease is the result of a genetic

mutation.

Causes & symptoms

Immunoglobulin deficiencies are the result of congenital defects

affecting the development and function of B lymphocytes (B-cells).

There are two main points in the development of B-cells when defects

can occur. First, B-cells can fail to develop into antibody-producing

cells. X-linked agammablobulinemia is an example of this disease.

Secondly, B-cells can fail to make a particular type of antibody or

fail to switch classes during maturation. Initially, when B-cells

start making antibodies for the first time, they make IgM. As they

mature and develop memory, they switch to one of the other four

classes of antibodies. Failures in switching or failure to make a

subclass of antibody leads to immunoglobulin deficiency diseases.

Another mechanism which results in decreased antibody production is a

defect in T-helper cells. Generally, defects in T-helper cells are

listed as severe combined immunodeficiencies.

Symptoms are persistent and frequent infections, diarrhea, failure to

thrive, and malabsorption (of nutrients).

Diagnosis

An immunodeficiency disease is suspected when children become ill

frequently, especially from the same organisms. The profile of

organisms that cause infection in patients with immunoglobulin

deficiency syndrome is unique and is preliminary evidence for this

disease. Laboratory tests are performed to verify the diagnosis.

Antibodies can be found in the blood. Blood is collected and analyzed

for the content and types of antibodies present. Depending on the

type of immunoglobulin deficiency the laboratory tests will show a

decrease or absence of antibodies or specific antibody subclasses.

Treatment

Immunodeficiency diseases can not be cured. Patients are treated with

antibiotics and immune serum. Immune serum is a source of antibodies.

Antibiotics are useful for fighting bacteria infections. There are

some drugs that are effective against fungi, but very few drugs that

are effective against viral diseases.

Bone marrow transplantation can, in most cases, completely correct

the immunodefiency.

Prognosis

Patients with immunoglobulin defiency syndromes must practice

impecable health maintenance and care, paying particular attention to

optimal dental care, in order to stay in good health.

Terms:

Antibody

Another term for immunoglobulin. A protein molecule that specifically

recognizes and attaches to infectious agents.

T-helper cell

A type of cell that recognizes foreign antigens and activates T- and

B-cells in an immune response.