An Overview of Immunoglobulins

Immunoglobulins are also known as Igs, antibodies, immune globulins, gamma globulins, and immune serum globulins.

There are two standard definitions of Immunoglobulins:

1.  A solution sourced from human blood plasma, which has concentrated levels of antibodies that offer protection from certain diseases.

For instance, someone could have short-term protection from particular infections or even Rh sensitization while they’re pregnant. These solutions can be created using human blood plasma that is pooled and processed from sources of blood donations before undergoing purification.

2.  Special proteins made inside the human body as a response to foreign elements like viruses and bacteria. Plasma cells in lymphoid tissues and bone marrow make five different classes of immunoglobulins that bind to foreign substances and then neutralize them: A, D, E, G, and M.

This overview will concentrate on definition #2.

Immunoglobulin A (or IgA) is one of the more common immunoglobulins. It’s mostly present in bodily secretions. It’s also the primary antibody in saliva, tears, and the mucous membranes of the respiratory and gastrointestinal tracts.

Immunoglobulin D (or IgD) is found in small volumes in blood serum and considered functional in response to particular allergies.

Immunoglobulin E (or IgE) is often found in the mucous membranes and skin. It is thought to serve some capacity in allergic reactions and in response to environmental antigens.

Immunoglobulin G (or IgG) is widely prevalent throughout the body, offering long-term defense against antigens and most bacterial invasions.

Immunoglobulin M (or IgM) is a relatively big molecule and is found in the human bloodstream where it fights blood infections. It’s the initial or primary immunoglobulin to be produced after antigen exposure.

Immunoglobulins A, G, and M

Why Should You Get Tested?

Testing helps analyze the status of your immune system. It can also detect and/or monitor deficiency or excess in different classes of immunoglobulins.

When Should You Get Tested?

If you have chronic diarrhea or recurring infections, you should get tested. Also, it’s good to get tested if your doctor thinks there might be an excess or deficiency in a certain immunoglobulin. Routine testing is also useful in tracking circumstances that might impact immunoglobulin levels, be they genetic, like selective IgA deficiency, or acquired, as would be in the cases of HIV, AIDS, and multiple myeloma.

What Exactly Gets Tested?

Immunoglobulins serve a crucial function in the overall immune system of the human body. They are proteins created by certain immune cells known as plasma cells and are a response to viruses, bacteria, and a variety of other microorganisms. They can also be a response to exposures to numerous other substances that the body determines to be harmful antigens that aren’t part of the body. This testing measures immunoglobulin amounts for A, G, and M in your blood. In some cases, it also tests for them in your saliva or cerebrospinal fluid, also known as CSF.

When you are first exposed or infected with an antigen or foreign substance, your immune system is likely to recognize that the substance or microorganism as ‘non-self’ material that shouldn’t be there. In response, plasma cells are instigated to make particular immunoglobulin antibodies intended to bind to the threat and then neutralize it. If any recurring exposures happen, your immune system can ‘remember’ previously encountered antigens, which means additional antibodies are created quickly. In the event of subsequent exposure to microorganisms encountered before, this can help you avoid re-infection.

Immunoglobulins are classified into five distinct classes, with a number of subclasses. Every class categorizes a different collection of antibodies, and they all have minor variations in the functions they perform. Immunoglobulin classes include:

IgM (or Immunoglobulin M) antibodies are the first thing the human body makes when responding to any new infection or ‘non-self’ antigen. Providing a short duration of protection, these IgM antibodies are likely to increase for a few weeks before declining in favor of IgG production.

IgG (or Immunoglobulin G) constitutes 70 to 80 percent of all the immunoglobulins in your blood. Certain IgG antibodies are produced in the first case of exposure to an antigen or infection, growing in volume for several weeks before coming back down to a stable level. The human body keeps an inventory of IgG antibodies, which can see prompt reproduction if exposure to the same antigen happens again. It’s IgG antibodies that allow humans to enjoy long-running defense against the many microorganisms in nature. For individuals with typical immune systems, re-infection is frequently prevented with enough IgG production. Vaccinations take advantage of this particular process so that initial infections can be avoided, while the inventory of IgG antibodies is grown. This happens by exposing people to either antigens that stimulate microorganism identification or to a live-but-weakened microorganism. IgG is the one immunoglobulin capable of passing through a placenta. Thus, the IgG antibodies of the mother protect her fetus throughout pregnancy, as well as the first several months of a baby’s life after delivery. IgG has four subclasses, known as IcG1, IgG2, IgG3, as well as IgG4.

IgA (or Immunoglobulin A) makes up approximately 15 percent of all the immunoglobulins in a person’s blood. However, it’s also located in gastric secretions, respiratory secretions, tears, saliva, and even breast milk. IgA offers protection from infections in the body’s mucosal areas. These areas include the gastrointestinal tract, where the intestines and stomach are, as well as the respiratory tract, which includes the lungs and sinuses. As this immunoglobin can pass through breast milk from a mother to a child, it offers an infant gastrointestinal tract protection and benefits. Human babies don’t start producing substantial volumes of IgA until after six months after birth, which means any IgA the baby has in their blood before that is a result of mother’s milk they were fed.  IgA has two subclasses known as IgA1 and also IgA2.

IgD (or Immunoglobulin D) is a class of immunoglobulin where the function isn’t entirely understood, nor is it measured frequently.

IgE (or Immunoglobulin E) is associated with conditions like parasitic infections, allergies, and allergic diseases. Usually measured as a component of allergy testing blood panels, IgE is not normally incorporated into quantitative immunoglobulin testing.

Immunoglobulin testing is designed to measure the overall volume of major immunoglobulin classes without distinguishing between subclasses. Additional testing can measure the subclasses or look for particular antibodies.

Various conditions might increase or decrease immunoglobulin production. An increase is known as hypergammaglobulinemia, and a decrease is referred to as hypogammaglobulinemia. Some conditions can affect every class of immunoglobulins, while in other circumstances, only one class might be impacted. Some of these conditions are acquired, whereas others are inherited from a previous.

How Is This Used?

Testing is utilized to look for a deficiency or excess in the three primary immunoglobulin classes of IgM, IgG, and IgA. This testing provides valuable data about how healthy the immune system of the person being tested is. It can also assist in the diagnosis of different diseases and conditions that impact Ig levels in one or more of the three classes.

Typically, immunoglobulin disorders might be categorized as follows:

  • Immunoglobulin Excess
  • Monoclonal excess is where the extra immunoglobulins come from the clones of a single plasma cell
  • Polyclonal excess is where the extra immunoglobulins come from many different immune plasma cells
  • Immunoglobulin Deficiency
  • Primary (inherited) deficiencies are rare disorders where the human body can’t produce one or more immunoglobulin classes
  • Secondary (acquired) deficiencies are the most common deficiencies and are caused by an underlying factor or condition

This test can be ordered in conjunction with other tests, like a urine and/or serum protein electrophoresis, to diagnose and track conditions related to excessive or abnormal immunoglobulin production. In cases like these, urine samples might also be collected.

If the amount of one of the main immunoglobulin classes is excessive, then additional testing via immunofixation can be performed to ascertain whether or not the immunoglobulin comes from clones of an abnormal plasma cell (monoclonal gammopathy). Monoclonal gammopathies are present with cases of multiple myeloma, which is a malignancy of the plasma cells. A serum-free light chain test may also be conducted.

When Is This Ordered?

Doctors order the Immunoglobulins (IgA, IgG, IgM) test for patients with symptoms of deficient immunoglobulins, like chronic diarrhea or recurring infections of the digestive or respiratory tracts.

Additionally, immunoglobulins testing may get ordered if a person shows signs of chronic infection or inflammation, or just when a doctor thinks that immunoglobulin production might be abnormal or excessive. The Igs test may be ordered routinely to track the course of someone’s condition over time.

This test might also be performed on cerebrospinal fluid (or CSF) anytime a doctor thinks that a particular condition that’s impacting the patient’s central nervous system could be related to excess production of immunoglobulins.

What Do the Test Results Actually Mean?

The test results for IgM, IgA, and IgG levels are typically analyzed as a group. Abnormal test results frequently suggest that the immune system is being impacted by something, thus indicating the need for more testing. Immunoglobulin testing isn’t diagnostic on its own, but it does prove to be a rather robust indicator of some a condition or disease. Various conditions are known to be associated with decreases or increases in immunoglobulins.

Higher Levels

Higher levels of polyclonal immunoglobulins might occur in conjunction with numerous different conditions.

Monoclonal immunoglobulins can be seen in blood cell tumors involving plasma cells or lymphocytes. In such disorders, it’s common to see a definitive increase in one immunoglobulin class with a decrease happening in the remaining classes. Even though impacted people might have higher levels of immunoglobulins overall, they are, in actuality, immunocompromised since most of their immunoglobulin production is categorized as abnormal and doesn’t support the body’s immune response.

Here are particular instances of conditions which might result in increased levels of immunoglobulins.

A polyclonal increase in any or all of the three classes (A, G, M) may be associated with the following conditions:

  • Chronic inflammation
  • Inflammatory disorders
  • Autoimmune disorders (rheumatoid arthritis, systemic lupus erythematosus, scleroderma)
  • Hyperimmunization reactions
  • Cirrhosis
  • Wiskott-Aldrich syndrome
  • Acute and chronic infections

In a newborn: infection during pregnancy (CMV, rubella, toxoplasmosis, or congenital syphilis).

A monoclonal increase in a single class, either with or without corresponding decreases in the remaining two classes, may be associated with the following conditions:            

  •               CLL (or chronic lymphocytic leukemia)
  •              Multiple myelomas
  •              Lymphoma
  •              MGUS (or monoclonal gammopathy of undetermined significance)

             In the case of IgM: Waldenstrom’s macroglobulinemia

Low Levels

The most frequent reasons for a decrease in immunoglobulins are acquired underlying (secondary) conditions, which either impact the capacity of the body to make immunoglobulins or that just increase protein loss in the body.  Deficiencies can also result from corticosteroids, immunosuppressants, phenytoin, and carbamazepine, or due to toxins.

Here are certain instances of conditions which might result in decreased levels of immunoglobulins.

Conditions/factors that affect immunoglobulin production may be associated with the following conditions:

  • Drugs like immunosuppressants, phenytoin, and carbamazepine
  • Complications resulting from conditions like diabetes or kidney failure
  • Transient production delay in newborns, especially in premature infants (or transient hypogammaglobulinemia of infancy)

Conditions causing abnormal protein loss may be associated with the following conditions:

  • Nephrotic syndrome (a particular kidney disease where protein gets lost through the urine stream
  • Burns
  • Protein-losing enteropathy (any condition impacting the gastrointestinal tract and thus affecting protein absorption and/or digestion

Inherited immune deficiencies tend to be rare, and they’re frequently called primary immunodeficiencies. They might impact all immunoglobulin production, just one class, or various subclasses. These various disorders can include hyper-IgM syndrome, SCID (or severe combined immunodeficiency), Wiskott-Aldrich syndrome, ataxia-telangiectasia, x-linked agammaglobulinemia, agammaglobulinemia, and CVID (or common variable immunodeficiency).

In CSF, immunoglobulins typically are present in very low concentrations. 

Increased levels may be associated with conditions including inflammatory conditions:

  • Multiple sclerosis
  • Central nervous system infections like encephalitis and meningitis
  • A decrease in the level of salivary IgA might happen in patients with recurring infections of the respiratory tract

Why Did My Newborn Have an IgM Test?

Sometimes, this test is used to see if a newborn acquired an infection before birth.  Since IgM antibodies are too big to pass through a placenta from the mother to the baby in the womb, the presence of IgM antibodies indicates the infection began during pregnancy.

What Else Should I Be Aware Of?

Those with conditions resulting in lower immunoglobulin levels don’t enjoy robust immune responses to things like vaccinations. Their bodies might not make enough antibodies to result in appropriate protection. They also might not be able to receive live vaccines, like the ones used for measles or polio.

Quite a few lab tests can measure the levels of antibodies in a person’s blood, but anyone with immunoglobulin deficiencies might get false-negative results in their testing. Celiac disease is one thing that can get missed in standard testing, meaning that further testing might be suggested – for example, a celiac disease test for the IgA class of anti-tissue transglutaminase antibody (or anti-tTG).

When IgA or IgG concentrations are lower, or a subclass deficiency is suspected, then subclass testing can help identify the deficiency with more precision. Subclass deficiencies can happen even when class concentrations are within normal ranges.

Some patients who have IgA deficiencies can even develop anti-IgA antibodies. If a person who has anti-IgA receives a blood component transfusion which contains IgA, they may have a severe anaphylactic transfusion reaction.