The Myeloma Alphabet Soup Handbook
Immunoglobulins


Source: Bob Tindall
From a medical textbook titled Harrison's Principles of Internal Medicine, published in 1994.

1. A normal immunoglobulin consists of a heavy chain and a light chain. The heavy chain has a molecular weight of about 50,000. The light chain has a molecular weight of about 25,000.

2. Each heavy chain has four domains. Each light chain has two domains. A domain consists of about 100 amino acids.

3. The heavy and light chains are linked together by disulfide bonds.

4. There are ten types of heavy chains, called G1, G2, G3, G4; A1, A2; M1, M2; D, and E. There two types of light chains: one is called kappa and the other is called lambda.

5. The heavy chain determines the function of the immunoglobulin. Each type plays a different role in the immune defense strategy.

6. The prefix Ig stands for immunoglobulin. To classify the immunoglobulin, this prefix is followed by the letter G, A, M, D, or E (which defines the heavy chain) and the symbol k (kappa) or l (lambda) which defines the light chain.

IgA: Concentrates in body fluids -- tears, saliva, the secretions of the respiratory and gastrointestinal tracts -- guarding the entrances to the body. Normal range approximately (40 - 375 mg/dL)

IgD: Is almost exclusively found inserted into the membranes of B cells, where it somehow regulates the cell's activation.

IgE: Under normal circumstances occurs in trace amounts, probably evolved as a defense against parasites, but it is more familiar as the villain in allergic reactions.

IgG: The major immunoglobulin in the blood, is also able to enter tissue space; it works efficiently to coat microorganisms, speeding their uptake by other cells in the immune system. Normal range approximately (600 - 1500 mg/dL)

IgM: Usually combine in star-shaped clusters, tend to remain in the bloodstream, where it is very effective in killing bacteria. Normal range approximately (30 - 190 mg/dL)

7. Accordingly, immunoglobulin type IgG1k refers to an immunoglobulin whose heavy chain is type G1 and whose light chain is type kappa.

8. In myeloma, the immunoglobulins produced by the malignant plasma cell are not normal, but are mutants. It is common, however, to refer to the type of myeloma by the type immunoglobulin that is most closely approximated.

9. In myeloma, most of the cases (53%) are of type IgG. Another 25% is A. And about 20% are light chains only (no heavy chains). The light chains are obvious mutants.

10.In myeloma, the heavy chain can be monitored as an M (Monoclonal) spike. The M spike is a well known and convenient means of monitoring the progress of myeloma. Unfortunately, if the malignant plasma cell does not produce a heavy chain, then there is no M spike, and the myeloma must be monitored by some other means.

More information of Immunoglobulins: http://student.bio.geneseo.edu/htdocs/bio380/chin/Antibodies.html

Light Chains, Heavy Chains
Source: Mike Katz

Light chain, heavy chain, IgA, IgG-- they are all proteins manufactured by plasma cells. Normally, there are billions of plasma cells, with lots of different colors and flavors, each type dedicated to producing a particular protein that is good at fighting a particular infection or other threat to the body. It's like a symphony orchestra, with different strings, brass, percussion, etcetra, all playing in harmony. When there is a malignant plasma cell, it's like the second trombone is suddenly on a fertility drug, reproducing out of control, and, before you know it, the orchestra is inundated with second trombones-- and you can barely hear anyone else. So, if the plasma cell that's malignant normally produced light chains, you are knee deep in light chains. If it was IgG, then you've got too much IgG. Bottom line, it's not terribly significant which protein is being overproduced, although people do do various statistics on these distinctions. Treatments are generally similar, and they are all indicative of myeloma, which is a plasma cell malignancy. For the more technically inclined, Immunoglobulins normally look like the picture below:


Light Chain
         |
      H e a v y   C h a i n
         |
      H e a v y   C h a i n
         |
Light Chain


Light chains come in two flavors: kappa and lambda Heavy chains come in two flavors: A or G
IgA (immunoglobulin A) can look like either of the two pictures below:

Lambda Light Chain                     Kappa Light Chain
        |                                     |
   H e a v y   C h a i n   A             H e a v y   C h a i n   A
        |                                     |
   H e a v y   C h a i n   A             H e a v y   C h a i n   A
        |                                     |
Lambda Light Chain                     Kappa Light Chain


IgG (immunoglobulin G) can look like either of the two pictures below:

Lambda Light Chain                     Kappa Light Chain
        |                                     |
   H e a v y   C h a i n   G             H e a v y   C h a i n   G
        |                                     |
   H e a v y   C h a i n   G             H e a v y   C h a i n   G
        |                                     |
Lambda Light Chain                     Kappa Light Chain


"Free" Light chains or heavy chains can be produced as well, which just means that they are not assembled into the normal 4-piece immunoglobulin structures.
For more information on the immune system: Understanding the immune system; (P080) from the NCI
http://rex.nci.nih.gov/PATIENTS/INFO_TEACHER/bookshelf/NIH_immune/index.html

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Last Updated: 01/07/99