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Tests & Imaging > Labs > Immunoglobulins

Last Update: 12/16/2015

Topics

About Immunoglobulins | Common Immunoglobulins Values for Adults  | Resources

Hypogammaglobulinemia |   Intravenous Administration of Immunoglobulins | Rituxan-induced Hypogammaglobulinemia
 CLL and hypogammaglobulinemia | Immunoglobulins A to M

 

Immunoglobulins (Ig)- a large family of proteins, also known
as antibodies, providing a first-line of defense that protects the body from infection - foreign pathogens (virus, germs, parasites, etc.).

Produced by B cells, Igs play a central role in humoral immunity, and deficiency may result in dramatic consequences for the body's defense against infections.1  

These protective antibodies are divided into five major classes:
IgG, IgM, IgA, IgE, and IgD  

NOTE:  Rituxan treatment, particularly long term use, is associated with decreased serum immunoglobulins in some patients. See Hypogammaglobulinemia below.

While Ig infusions, may be considered in these situations -- when there is also an increased incidence of infection -- and this way of supplementing antibodies requires infusions on a regular basis and is not without risks and costs.   See for reducing risks: http://www.cidpusa.org/ivig.html


 

Common Immunoglobulins Values for Adults

Normal Immunoglobulin levels vary by lab because of differences in testing techniques. Reading can also vary for adults versus children.
 

IgA Immunoglobulin A

Protects against infections of the mucous membranes lining the mouth, airways, digestive tract

Est. Normal Range: 
80 - 350 mg/dl

IgG  Immunoglobulin G

M
ajor type of antibody found in the blood that can enter tissues; 
fights infection.
Est. Normal Range: 
620 - 1400 mg/dl
IgM Immunoglobulin M

Remains in the bloodstream where it can kill bacteria. 
Elevated levels associated with Waldenström’s Macroglobulinemia
Est. Normal Range: 
45 - 250 mg/dl
IgD Immunoglobulin D

Remains in the bloodstream to fight bacteria

Est. Normal Range:
.3 - 3.0 mg/dl

IgE Immunoglobulin E

Frequently increased in parasitic infestations and atopic individuals (with allergic hypersensitivity)

Est. Normal Range: 
.002 - .2 mg/dl

 


Resources

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About immunoglobulins webMD.com  | NCI background on antibodies 
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About Hypogammaglobulinemia (detailed and technical) Emedicine
Author: Robert Y Lin, MD; Chief Editor: Michael A Kaliner, MD
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Immunoglobulins Test Results  webMD.com
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* IDF
Immune Deficiency Foundation - Immunoglobulin Therapy & Other Medical Therapies for Antibody Deficiencies http://bit.ly/1qsFlls
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Immunoelectrophoresis (IEP) Test
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Immunoglobulin Explanation by Guy Sherwood
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IgG Deficiencies | Johns Hopkins Medicine Health Library http://bit.ly/1IF07Va

Rituxan-induced Hypogammaglobulinemia - low levels of immunoglobulins (Igs) -

a common side effect of Rituximab maintenance;
associated with other treatments and lymphoma as well

Scholar Topic Search | PubMed

Immunoglobulins (Igs) made by B cells play a central role in humoral immunity, and low levels of Ig may limit the body's ability to fight infections. The symptoms depend on the type and severity of the Ig deficiency and the presence or deficiency of cellular immunity.  Generally, providing Ig antibody by infusion (IV) is only done when there are recurrent or persistent infections. 
In general, when hypogammaglobulinemia (low Ig levels) leads to recurrent infections  ... these mainly occur in the upper and lower airways, although bacteremia and GI infections can also occur..1  

The reported incidence of symptomatic hypogammaglobulinemia  is about 7-10%.

Key facts and questions related to Rituximab Maintenance:
bullet

The risks of a therapy must be weighed against the potential benefits - the risks of the disease untreated or treated differently.

bullet

Deficiencies in Igs do not always lead to infectious complications or the need to receive Intravenous Ig.

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Do the benefits of Rituximab maintenance (improved PFS on average) outweigh the long-term risks?

bullet

What is the clinical significance of low Igs occurring from Rituximab maintenance?  Is it reversible?

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In one retrospective study, 55% of the patient receiving Rituxan maintenance developed Ig deficiencies.
Of these, 20% (10/49) required intravenous Ig.

  1. About Hypogammaglobulinemia (detailed and technical) Emedicine
    Author: Robert Y Lin, MD; Chief Editor: Michael A Kaliner, MD
  2. JCO, 2010: Hypogammaglobulinemia (hypogam) -
    the impact of rituximab maintenance. http://bit.ly/o1GMpo

    Snapshot:

    Retrospective study of 183 pts with normal (baseline) serum
    immunoglobulin (sIg) levels prior to Rituximab
      26.7% (49) received
    Rituximab Maintenance while
      73.2% (134) received as monotherapy (I) or Rituxan with chemotherapy (CI).

    Hypogam was documented in 39% (71/183) of pts with baseline normal sIg levels following Rituximab

    Rituximab Maintenance (RM) was associated with a higher risk of developing hypogam,
      55% (27/49) compared to
      33% (44/134) receiving I or CI alone, p=0.006.

    IVIG was administered to 13% (23/183) of pts with normal baseline sIg.
    Among patients who received RM,
      20% (10/49) received IVIG compared to
      10% (13/134) among patients treated with I or CI alone, p=0.05.

    IVIG for treatment of symptomatic hypogam was administered to
    10% (18/183) of pts with normal sIg prior to Rituximab therapy (of any kind).
  3. Blood. 2002 Sep 15;100(6):2257-9
    Rituximab treatment results in impaired secondary humoral
    immune responsiveness. PMID: 12200395
    | Related articles
  4. Incidence of Hypogammaglobulinemia in Pts Receiving Rituximab and Use of IV Immunoglobulin for Recurrent Infections http://1.usa.gov/1I0ihGA

    "Given the findings observed in this data set, we believe that clinicians should be aware of the increased risk for symptomatic hypogammaglobulinemia in the setting of rituximab use, particularly with the increased frequency of rituximab use for maintenance. In the absence of an overall survival advantage, the 6.6% risk of symptomatic hypogammaglobulinemia and eventual requirement of IVIG should be considered when deciding whether to use maintenance rituximab."
  5. eMedicine:  Hypogammaglobulinemia: Practice Essentials, Background, Pathophysiology http://bit.ly/1UzHGsG

    Treatment of secondary hypogammaglobulinemia is directed at the underlying cause, as follows:

    • IVIG is not indicated for lymphoproliferative disorders unless immunoglobulin levels are low in association with recurrent infections or if IVIG is being used for autoimmune conditions that may accompany these disorders

Mike's experience with symptomatic hypogammaglobulinemia

"IVIG is not like getting injections of vitamins or minerals, not by a long shot."

Having an easy experience with R, I did not expect anything near what actually happened the second time I received IVIG.  The abstract mentions symptomatic hypogammaglobulinemia, aka low IgG in laymen's terms. While upper respiratory infections, sinus infections, bronchitis, and the occasional pneumonia are typically reported, the "symptomatic" can include an assortment of other issues.

... I can tell when my IgG is getting below 400, as I feel stiff, achy, and low on energy. I started IV iG due to bacterial overgrowth in the lower GI tract, which I understand also to be fairly common with Rituxan. The symptoms were like an unrelenting case of IBS--- cramping, bloating, gas, and a constant mild-moderate pain in the lower left abdomen. Antibiotics were tried first, followed by probiotics. These treatments worked, but a few weeks later, the symptoms would return.

Fortunately, I get far more than the typical month out of an IVIG treatment. I fear the stuff, and use it as sparingly as I can get away with, perhaps at the beginning and end of the winter season. I am 3 years out from Rituxan now, and hoping the IV iG extends the remission, especially since I originally had autoimmune issues AIHA/ITP when diagnosed 6 years ago, enlarging the spleen with cells prematurely destroyed by warm IgG antibody.

I have had some bad reactions to IVIG, including alarming stage 2 hypertension, and anxiety, including the physical symptoms thereof. It must have created certain chemical imbalances. I was in full panic attack mode on the 2nd treatment when my blood pressure went sky high. I do recall that I broke one of their automated blood pressure machines when they tried to use it on me one too many times that day. Not sure how often something like this happens, but IV iG is not like getting injections of vitamins or minerals, not by a long shot.

I used to get my self to and from Rituxan treatments by myself without any trouble. With IV iG, I make sure there is someone to drive me home.

In my case, the alternative was to lose my spleen, and that was something I sought to avoid. I would do Rituxan alone again given the 6 years of benefit it has produced.

Editor's note: the risk of symptomatic hypogammaglobulinemia from Rituxan is about 7 to 10% ... according to reports summarized above.
 

CLL and hypogammaglobulinemia

Hypogammaglobulinemia is present in 25% of patients with newly diagnosed CLL. Approximately 25% of patients who have CLL with normal IgG levels at diagnosis will subsequently develop hypogammaglobulinemia on long-term follow-up. The presence of hypogammaglobulinemia does not appear to impact overall survival.

Source:  Hypogammaglobulinemia in newly diagnosed CLL: Natural history, clinical correlates, and outcomes. - http://1.usa.gov/1T4qDNL

Intravenous Administration of Immunoglobulins

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Safety and Adverse Events Profiles of Intravenous Gammaglobulin Products Used for Immunomodulation: A Single-Center Experience  cjasn.asnjournals.org

It is important to understand that all IVIg products are not alike. They differ in salt and sugar content, pH, and osmolality. Careful attention to the products that are provided by an institution’s pharmacy is critical to avoid excipient-related adverse effects. On the basis of our experience, all IVIg products can be administered safely if adverse effect profiles are recognized and appropriate patient selection and premedications are given. Because the use and indications for IVIg continue to expand and higher doses and volumes are mandated for autoimmune and inflammatory disorders, it is critical to be aware of the potential adverse effects that are associated with specific products and, more important, how to prevent them.
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Intravenous immunoglobulin for the prevention of infection in CLL. nejm.org

A randomized, controlled clinical trial. Cooperative Group for the Study of Immunoglobulin in Chronic Lymphocytic Leukemia
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FDA: Immune Globulin Subcutaneous (Human), Vivaglobin http://bit.ly/bnpmBH 
indication: Primary Immune Deficiency (PID)
 


Immunoglobulins A to M

IgA

Immunoglobulin A

Est. Normal Range: 
80 - 350 mg/dl

Lab-specific
Varies by age

Return to top

 

Immunoglobulin A (IgA) is a type of antibody that protects against infections of the mucous membranes lining the mouth, airways, and digestive tract.

bullet
About webMD
bullet
SELECTIVE IgA DEFICIENCY merck.praxis.MD 
 
"Selective IgA deficiency is defined as less than 5 mg/dL of serum IgA in the presence of normal concentrations of IgM and IgG. Among the B-cell disorders it is the most commonly identified deficiency. It occurs in one in every 500 to 1000 individuals in Europe and the United States. It is less common in those of African-American or Asian descent ... "

IgD

immunoglobulin D

Est. Normal Range:
.3 - 3.0 mg/dl
 
Lab-specific
Varies by age 

    

Return to top
IgD, immunoglobulin D is mainly found on the surface of B-cells and may help regulate B-cell function.  The function of circulating IgD is unknown.
 
bullet
About webMD
bullet
Immunoglobulin D Deficiency emedicine

IgE

immunoglobulin E

Normal Range: 
.002 - .2 mg/dl

Lab-specific
Varies by age
    

Return to top
IgE, immunoglobulin E - the protective role is not clear. IgE is frequently increased in parasitic infestations and atopic individuals. 

IgE myeloma is extremely rare and should be sought after abnormal protein electrophoresis (restriction) and/or abnormal kappa/lambda ratio unexplained by IgG, IgA, or IgM. IgE is elevated 4-30 times normal in various diseases, among which atopic disorders and parasitic disorders are most prominent. The principal limitation of this test is the wide overlapping range of IgE values between atopic and nonatopic disease states.
.
 
bullet
About webMD

IgG

immunoglobulin G

Est. Normal Range: 
620 - 1400 mg/dl

Lab-specific
Varies by age

Return to top
IgG, immunoglobulin G - the major antibody found in the blood that can enter tissues. It coats germs, helping other cells to seek and destroy them.
 
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About IgG  wikipedia.org (NEW) |webMD
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IgG subclasses in healthy children and adults xs4all.nl
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IgG subclasses and humoral immunity - xs4all.nl 

IgM

immunoglobulin M

Est. Normal Range: 
45 - 250 mg/dl

Lab-specific
Varies by age

Return to top
IgM, immunoglobulin M - an antibody that remains in the bloodstream where it can kill bacteria that enter the blood stream.  Elevated levels of IgM are associated with Waldenström’s Macroglobulinemia
 
"IgM in normal serum is often found to bind to specific antigens, even in the absence of prior immunization. For this reason IgM has sometimes been called a "natural antibody". This phenomenon is probably due to the high avidity of IgM that allow it to bind detectably even to weakly cross-reacting antigens that are naturally occurring in nature" 1
  1. About IgM  wikipedia.org (NEW) | webMD

Immuno-electrophoresis
serum/urine

Return to top

Detects the presence or absence of Immunoglobulins in the urine and assesses the qualitative character (polyclonal vs. monoclonal) of the immunoglobulins [1]

Normal Values: No, or small amount, of protein in the urine. 
Abnormal: Immunoglobulin (antibodies) in the urine.

Possible indications: Kidney disorders, multiple myeloma, Macroglobulinemia of Waldenstrom's, chronic lymphocytic leukemia, a single clone of lymphocytes produces one type of immunoglobulin -- a monoclonal immunoglobulin. This is identifiable as monoclonal by immunoelectrophoresis. You can have monoclonal immunoglobulins, without it being a cancer, however.

  1. About urine - baptistnortheast.com
 
Disclaimer:  The information on Lymphomation.org is not intended to be a substitute for 
professional medical advice or to replace your relationship with a physician.
For all medical concerns,  you should always consult your doctor. 
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