Hypergammaglobulinemia

When serum total protein is markedly increased due to a selective hyperglobulinemia, an increase in gammaglobulins may be suspected. Serum protein electrophoresis can be used to further investigate this increase and, in addition, the shape of the peak on the electrophoretogram may provide important clues as to the cause of the elevation. Chronic antigenic stimulation normally results in a polyclonal hyperglobulinemia with a broad-based, rounded peak in the γ region due to the synthesis of myriad types of immunoglobulins to various antigenic epitopes on the offending agent(s) (see Case 2: Zed). For example, chronic pyelonephritis in cattle may be associated not just with hyperfibrinogenemia, but also polyclonal hypergammaglobulinemia. Feline infectious peritonitis also classically produces a polyclonal hypergammaglobulinemia.

However, when gammaglobulins are increased due to an immunoglobulin-producing B cell or plasma cell tumor, a narrow-based pattern is seen with one or two sharp peaks, described as a monoclonal or biclonal gammopathy (see Case 2: Katie in Chapter 3: Hemopoietic Neoplasia). The base of this peak in the gamma region is typically similar to the narrow base of the albumin peak on the same electrophoretogram. A sharp peak is produced because the tumor cells are synthesizing a single (or sometimes 2) abnormal immunoglobulin(s). Occasionally, the abnormal immunoglobulin will migrate to the β or even α globulin region rather than the γ region. When a mono or biclonal gammaglobulin peak is identified, radial immunodiffusion can be done to identify the particular immunoglobulin that is being produced in excess. Immunoelectrophoresis and immunofixation can also be performed to further characterize the abnormal protein by utilizing species-specific antibody to the various types of immunoglobulin (IgG, IgM, IgA, and kappa and lambda light chains).

Although unusual, chronic antigenic stimulation due to certain agents, such as dimorphic fungi and Ehrlichia, may produce a narrow-based pattern rather than the broad-based polyclonal peak expected with infectious disease. This is referred to as an oligoclonal gammopathy (“oligo-“ meaning “few”), or a polyclonal gammopathy with restricted migration. Differentiation between chronic antigenic stimulation and B or plasma cell neoplasia can be difficult under these circumstances. The concurrent existence of both conditions is also possible (see Chapter 3: Hemopoietic Neoplasia).