Structure

All immunoglobulins have the same basic structure and consist of two identical ‘light’ and two identical ‘heavy’ polypeptide chains, held together by disulphide bridges (Fig 26.1). The light chains may be either of two types: kappa or lambda. The heavy chains may be of five types: alpha, gamma, delta, epsilon and mu. The immunoglobulins are named after their heavy chain type, as IgA, IgG, IgD, IgE and IgM.

The molecules are characterized by two functional areas:

The various classes of immunoglobulins have different tertiary structure and functions (Table 26.1). The major antibodies in the plasma are IgG, IgA and IgM.

Electrophoresis of serum proteins

Electrophoresis may be carried out to study a number of protein abnormalities. The normal pattern is shown in Figure 26.2(a). Immunoglobulins are detected primarily in the gamma globulin area on electrophoresis. Electrophoresis can show gross deficiency or excess of immunoglobulins and the presence of discrete bands (paraproteins) (Fig 26.2, b and c). Serum should be used for electrophoresis, as the fibrinogen of plasma (consumed during clotting) gives a discrete band that can easily be mistaken for a paraprotein. A quantitative measure of each protein class may be obtained by scanning the electrophoresis strip (Fig 26.3).

Measurement

Immunoglobulins may be measured in a number of ways, the necessity for the request often being triggered by an observed increase in the ‘globulin’ fraction (p. 50). If an abnormality is detected, then the particular type of immunoglobulin, or indeed of light or heavy chains where these are produced alone, may be confirmed by immunofixation or quantitatively by other means.

Increased immunoglobulins

Immunoglobulins may be increased non-specifically in a wide variety of infections and also in autoimmune disease. This increased synthesis comes from a number of cell lines, each producing its own specific immunoglobulin. The response is therefore said to be ‘polyclonal’ and results in a diffuse increase in protein mass throughout the gamma globulin region on electrophoresis. This is because the immunoglobulins produced by individual cell lines are slightly different from each other in terms of size and charge, and so do not migrate to the same place on electrophoresis. In contrast, cells from a single clone all make identical antibodies. As the cells multiply the immunoglobulin production becomes large enough to be observed on electrophoresis as a single discrete band. This may be an intact immunoglobulin or a fragment and is called a paraprotein.

Deficiencies or absence of immunoglobulins

Deficiencies or absence of immunoglobulins can occur as a result of infection, genetic abnormalities or the effects of therapy (Table 26.2). Where the situation is irreversible, replacement therapy has been used, either by addition of immunoglobulin-rich plasma or by the transplantation of bone-marrow-containing competent plasma cells.