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Plasma proteins (as it relates to immunity and multiple myeloma)

5 main types of blood proteins

  1. Albumin
  2. Globulin
  3. Fibrinogen
  4. Regulatory protein
  5. Clotting factors

In this article we will mainly be focusing on albumin and globulins.

Roles of albumin include

  • Maintaining oncotic pressure
  • Transportation of insoluble substances
    • Examples of endogenous substances include thyroid hormone, steroids and fatty acids
    • Examples of exogenous drugs that are albumin bound include warfarin and phenytoin

Types and roles of globulin include

Types

  • Alpha globulin
  • Beta globulin
  • Gamma globulin

Roles of globulin

Alpha and beta globulin are synthesized in the liver and act as carrier proteins as well as enzymes in the body.

Examples of alpha-1 globulin include alpha-1 antitrypsin (relevant to COPD), HDL, and thyroxin binding globulin. Examples of alpha-2 globulin include VLDL (related to cholesterol pathway), haptoglobin (which “mops” up free hemoglobin in serum), and prothrombin. Examples of beta globulins include LDL and complement proteins C3 and C4.

Gamma globulins mainly include antibodies (also called immunoglobulins) although some examples of other gamma globulins include CRP and alpha fetoprotein. There are 5 main types of immunoglobulins, depending on the type of heavy chain associated with it. In other words, the heavy chain determines the class of antibody (e.g. IgG vs IgA vs IgD, etc.), and there are 5 different types of heavy chains (M, D, G, A, E). Each immunoglobulin is composed of 2 heavy chains and 2 light chains.

File:Antibody je2.png - Wikimedia Commons
The variable region is also known as the Fab region or the fragment-antigen binding region. There are 2 such fragments on each immunoglobulin. The constant fragment region is also known as the Fc region, which is composed of just 2 heavy chains.

There are 2 types of light chains: kappa and lambda. Which means while there are 5 main classes of immunoglobulins (based on the 5 classes of heavy chains), in total there are a total of 10 different possible immunoglobulins, since each major class of immunoglobulin can be associated with either a kappa light chain or lambda light chain.

  • IgM
    • IgM kappa
    • IgM lambda
  • IgD
    • IgD kappa
    • IgD lambda
  • IgG
    • IgG kappa
    • IgG lambda
  • IgA
    • IgA kappa
    • IgA lambda
  • IgE
    • IgE kappa
    • IgE lambda

Hyperglobulinemia

Expect albumin to be elevated in dehydration.

Expect the alpha and beta globulins to be elevated in conditions such as

  • Acute phase reaction
  • Pregnancy
  • Nephrotic syndrome (due to hyperlipidemia i.e. increases in LDL and VLDL)
  • Hyperthyroidism
  • Iron deficiency anemia

Polyclonal vs Monoclonal gammopathies

Polyclonal gammopathies are due to conditions that cause a normal, expected and physiological increase in the production of immunoglobulins – these conditions are typically infectious or inflammatory. Polyclonal means that there are different plasma cells and each plasma cells produces a different kind of antibody.

  • Infectious
    • Hepatitis
    • HIV
    • TB
    • Bacterial infections
  • Inflammatory
    • Rheumatoid arthritis, lupus
    • Cancer

Monoclonal gammopathies are due to a wide spectrum of disease which includes multiple myeloma in which there is neoplasm of B cells. Since each B cell can only produce one type of antibody, this malignant B cell reproduces out of control, which results in the production of a single type of antibody. Since the body requires multiple forms of antibodies to maintain its humoral immunity, this antibody overcrowding that occurs results in a functional immunoglobulin deficiency.

An SPEP (serum protein electrophoresis) is required to differentiate between a polyclonal and monoclonal gammopathy. If the gammopathy is polyclonal then the gamma peak will be broad and not tall. If the gammopathy is monoclonal then the gamma peak will be narrow and very tall.

This image has an empty alt attribute; its file name is 220px-Electrophoresis.png
https://www.youtube.com/watch?v=YPkmSafckQA for a video explanation

More information on SPEP, UPEP, and immunofixation will be found in our article on multiple myeloma.