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Immunoglobulins 

  • Author: Rakesh Vadde, MBBS; Chief Editor: Eric B Staros, MD  more...
 
Updated: Jul 01, 2013
 

Reference Range

Immunoglobulins are glycoprotein molecules that are produced by plasma cells in response to an immunogen. Indications for serum immunoglobulin testing include diagnosis and monitoring of monoclonal gammopathies and immune deficiencies.

Reference ranges of immunoglobulins may vary based on sex and factors such as alcohol use, smoking status, and chronic conditions (eg, diabetes/metabolic syndrome) (see Considerations).

The reference range of immunoglobulin G (IgG) based on age is as follows:

  • Age 0-1 years: 231-1411 mg/dL
  • Age 1-3 years: 453-916 mg/dL
  • Age 4-6 years: 504-1464 mg/dL
  • Age 7-9 years: 572-1474 mg/dL
  • Age 10-11 years: 698-1560 mg/dL
  • Age 12-13 years: 759-1549 mg/dL
  • Age 14-15 years: 716-1711 mg/dL
  • Age 16-19 years: 549-1584 mg/dL
  • Older than 19 years: 700-1600 mg/dL

The reference range of immunoglobulin A (IgA) based on age is as follows:

  • Age 0-1 years: 0-83 mg/dL
  • Age 1-3 years: 20-100 mg/dL
  • Age 4-6 years: 27-195 mg/dL
  • Age 7-9 years: 34-305 mg/dL
  • Age 10-11 years: 53-204 mg/dL
  • Age 12-13 years: 58-358 mg/dL
  • Age 14-15 years: 47-249 mg/dL
  • Age 16-19 years: 61-348 mg/dL
  • Older than 19 years: 70-400 mg/dL

The reference range of immunoglobulin M (IgM) based on age is as follows:

  • Age 0-1 years: 0-145 mg/dL
  • Age 1-3 years: 19-146 mg/dL
  • Age 4-6 years: 24-210 mg/dL
  • Age 7-9 years: 31-208 mg/dL
  • Age 10-11 years: 31-179 mg/dL
  • Age 12-13 years: 35-239 mg/dL
  • Age 14-15 years: 15-188 mg/dL
  • Age 16-19 years: 23-259 mg/dL
  • Older than 19 years: 40-230 mg/dL

Table 1. IgG Subclasses (Open Table in a new window)

Age IgG Subclass 1 (mg/dL) IgG Subclass 2 (mg/dL) IgG Subclass 3 (mg/dL) IgG Subclass 4 (mg/dL)
Cord 435-1084 143-453 27-146 1-47
0-2 mo 218-496 40-167 4-23 1-33
3-5 mo 143-394 23-147 4-100 1-14
6-8 mo 190-388 37-60 12-62 1-30
9-35 mo 286-680 30-327 13-82 1-65
3-4 y 381-884 70-443 17-90 1-116
5-6 y 292-816 83-513 8-111 1-121
7-8 y 422-802 113-480 15-133 1-84
9-10 y 456-938 163-513 26-113 1-121
11-12 y 456-938 147-493 12-179 1-168
13-14 y 347-993 140-440 23-117 1-83
Adults 422-1292 117-747 41-129 1-291
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Interpretation

Conditions associated with a polyclonal or oligoclonal increase in serum immunoglobulin levels include the following:

Conditions associated with a monoclonal increase in serum immunoglobulin levels include the following:

Conditions associated with a decrease in serum immunoglobulin levels include the following:

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Collection and Panels

Specifics for collection and panels are as follows:

  • Specimen type: Blood serum
  • Container: Vacutainer, gold top or gel-barrier tube
  • Collection method: Venipuncture
  • Specimen volume: 1 mL
  • Methodology: Immunologic
  • Other instructions: Serum protein electrophoresis is required to distinguish between polyclonal and monoclonal immunoglobulin increases
  • Limitation: The test is not suitable for the measurement of samples containing rheumatoid factor, paraproteins, circulating immune complexes, lipemic or hemolyzed samples owing to unpredictable degree of light scatter

Related tests: Serum protein electrophoresis, total protein, serum complement, serum immunoglobulin free light chains

Serum vacuette 6-mL tube. Serum vacuette 6-mL tube.
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Background

Description

Immunoglobulins are glycoprotein molecules that are produced by plasma cells in response to an immunogen. The immunoglobulins derive their name as they migrate with globular proteins when antibody-containing serum is placed in an electrical field.

The immunoglobulins are divided into 5 different classes, based on differences in the amino acid sequences in the constant region of the heavy chains. All immunoglobulins within a given class have very similar heavy chain constant regions. These differences can be detected by sequence studies or more commonly by serological means (ie, via antibodies directed to these differences), as follows:

  • IgG - Gamma heavy chains
  • IgM - Mu heavy chains
  • IgA - Alpha heavy chains
  • IgD - Delta heavy chains
  • IgE - Epsilon heavy chains

The classes of immunoglobulins can be divided into subclasses based on small differences in the amino acid sequences in the constant region of the heavy chains. All immunoglobulins within a subclass have very similar heavy chain constant region amino acid sequences. Again, these differences are most commonly detected with serological means.

IgG subclasses are as follows:

  • IgG1 - Gamma 1 heavy chains
  • IgG2 - Gamma 2 heavy chains
  • IgG3 - Gamma 3 heavy chains
  • IgG4 - Gamma 4 heavy chains

IgA subclasses are as follows:

  • IgA1 - Alpha 1 heavy chains
  • IgA2 - Alpha 2 heavy chains

Immunoglobulins can also be classified by their type of light chain. Light chain types are based on differences in the amino acid sequence in the constant region of the light chain. These differences are detected with serological means. The light chains can be further divided into subtypes based on differences in the amino acid sequences in the constant region of the light chain, as follows:

  • Kappa light chains
  • Lambda light chains (Lambda 1, Lambda 2, Lambda 3, Lambda 4)

Quantitative immunoglobulins testing is used to measure levels of the 3 major immunoglobulin classes—IgG, IgA, and IgM—which make up 80%, 15%, and 5%, respectively, of normal serum immunoglobulins.

Indications/Applications

Indications for serum immunoglobulin testing include diagnosis and monitoring of monoclonal gammopathies and immune deficiencies.

Considerations

Median IgA values may be 20% higher in males, whereas median IgM values may be 30% higher in females. Sex differences in immunoglobulin concentrations, specifically high IgM levels in females, have been attributed to hormonal effects on B lymphocytes.[1, 2]

Alcohol consumption is associated with increased serum IgA levels, being higher in heavy drinkers than in light-to-moderate drinkers and abstainers. IgA increase in heavy drinkers is selective, not affecting IgM or IgG. In fact, serum IgG concentrations tend to be lower in moderate alcohol consumers than in abstainers.[3]

Smoking is associated with decrease in IgG levels.[3] Significant immunomodulatory effects occur with both smoking and alcohol consumption.[4]

Diabetes mellitus/metabolic syndrome is associated with increased IgA concentrations. It is associated with hyperglycemia, triglyceridemia, and abdominal obesity. These 3 factors selectively affect only the IgA class, with the exception of an IgM increase in individuals with dyslipidemia. There is a correlation between increase in IgA and interleukin 6 (IL-6), which are both elevated in chronic inflammatory disorders.

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Contributor Information and Disclosures
Author

Rakesh Vadde, MBBS Fellow in Pulmonary Medicine, Interfaith Medical Center

Rakesh Vadde, MBBS is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Thoracic Society

Disclosure: Nothing to disclose.

Coauthor(s)

M Frances J Schmidt, MD Chief of Pulmonary Medicine, Pulmonary Fellowship Program, Teaching Attending Physician, Department of Medicine, Interfaith Medical Center

M Frances J Schmidt, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians

Disclosure: Nothing to disclose.

Chief Editor

Eric B Staros, MD Associate Professor of Pathology, St Louis University School of Medicine; Director of Clinical Laboratories, Director of Cytopathology, Department of Pathology, St Louis University Hospital

Eric B Staros, MD is a member of the following medical societies: American Medical Association, American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology

Disclosure: Nothing to disclose.

Acknowledgements

Maximo Mora, Director of Clinical Laboratories, Department of Pathology, Interfaith Medical Center

References
  1. Kanda N, Tamaki K. Estrogen enhances immunoglobulin produc- tion by human PBMCs. J Allergy ClinImmunol. 1999. 103:282–8. 37.

  2. Bouman A, Heineman MJ, Faas MM. Sex hormones and the immune response. Hum Reprod Update. 2005. 11:411–23.

  3. McMillan SA, Douglas JP, Archbold GPR, McCrum EE, Evans AE. Effect of low to moderate levels of smoking and alcohol consumption on serum immunoglobulin concentrations. J ClinPathol. 1997. 50:819–22.

  4. A. Gonzalez-Quintela R, Alende F, Gude J, et al. Vidal: Serum levels of immunoglobulins (IgG, IgA, IgM) in a general adult population and their relationship with alcohol consumption, smoking and common metabolic abnormalities. Clinical and Experimental Immunology doi:. 2007. 10.1111/j:1365-2249.03545.

  5. Directory of services and interpretive guide 2010-2012, LabCorp.

  6. Hotamisligil GS. Inflammation and metabolic disorders. Nature. 2006. 444:860–7.

  7. Rodriguez-Segade S, Camina MF, Carnero A et al. High serum IgA concentrations in patients with diabetes mellitus: age wise distribution and relation to chronic complications. Clin Chem. 1996. 42:1064–7. 21.

 
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Serum vacuette 6-mL tube.
Table 1. IgG Subclasses
Age IgG Subclass 1 (mg/dL) IgG Subclass 2 (mg/dL) IgG Subclass 3 (mg/dL) IgG Subclass 4 (mg/dL)
Cord 435-1084 143-453 27-146 1-47
0-2 mo 218-496 40-167 4-23 1-33
3-5 mo 143-394 23-147 4-100 1-14
6-8 mo 190-388 37-60 12-62 1-30
9-35 mo 286-680 30-327 13-82 1-65
3-4 y 381-884 70-443 17-90 1-116
5-6 y 292-816 83-513 8-111 1-121
7-8 y 422-802 113-480 15-133 1-84
9-10 y 456-938 163-513 26-113 1-121
11-12 y 456-938 147-493 12-179 1-168
13-14 y 347-993 140-440 23-117 1-83
Adults 422-1292 117-747 41-129 1-291
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