Tests & Imaging > Labs > Immunoglobulins

Last Update: 09/06/2018

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 Source: emedicine.medscape.com	Age 0-1 years: 0-83 mg/dL Age 1-3: 20-100 mg/dL Age 4-6: 27-195 mg/dL Age 7-9: 34-305 mg/dL Age 10-11: 53-204 mg/dL Age 12-13: 58-358 mg/dL Age 14-15: 47-249 mg/dL Age 16-19: 61-348 mg/dL Older than 19: 70-400 mg/dL
IgG  Immunoglobulin G Major type of antibody found in the blood that can enter tissues; fights infection.   Source: emedicine.medscape.com	Age 0-1: 231-1411 mg/dL Age 1-3: 453-916 mg/dL Age 4-6: 504-1464 mg/dL Age 7-9: 572-1474 mg/dL Age 10-11: 698-1560 mg/dL Age 12-13: 759-1549 mg/dL Age 14-15: 716-1711 mg/dL Age 16-19: 549-1584 mg/dL Older than 19: 700-1600 mg/dL
IgM Immunoglobulin M Remains in the bloodstream where it can kill bacteria. Elevated levels associated with Waldenström’s Macroglobulinemia   Source: emedicine.medscape.com	Age 0-1: 0-145 mg/dL Age 1-3: 19-146 mg/dL Age 4-6: 24-210 mg/dL Age 7-9: 31-208 mg/dL Age 10-11: 31-179 mg/dL Age 12-13: 35-239 mg/dL Age 14-15: 15-188 mg/dL Age 16-19: 23-259 mg/dL Older than 19: 40-230 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

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

	The risks of a therapy must be weighed against the potential benefits - the risks of the disease untreated or treated differently.
	Deficiencies in Igs do not always lead to infectious complications or the need to receive Intravenous Ig.
	Do the benefits of Rituximab maintenance (improved PFS on average) outweigh the long-term risks?
	What is the clinical significance of low Igs occurring from Rituximab maintenance?  Is it reversible?
	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

	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.
	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
	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

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

	About webMD
	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 
    

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IgE

immunoglobulin E

Normal Range: 
.002 - .2 mg/dl

Lab-specific
Varies by age
    

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IgG

immunoglobulin G

Est. Normal Range: 
620 - 1400 mg/dl

Lab-specific
Varies by age

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IgM

immunoglobulin M

Est. Normal Range: 
45 - 250 mg/dl

Lab-specific
Varies by age

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1. About IgM  wikipedia.org (NEW) | webMD

Immuno-electrophoresis
serum/urine

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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