Gammopathies are conditions in which serum immunoglobulin levels are greatly increased. They can be classified either as polyclonal (increases in all major immunoglobulin classes) or monoclonal (increases in a single homogeneous immunoglobulin).
Polyclonal gammopathies involve chronic stimulation of the immune system. These include chronic pyodermas; chronic viral, bacterial, or fungal infections; granulomatous diseases; abscessation; chronic parasitic infections; chronic rickettsial diseases, such as tropical canine pancytopenia; chronic immunologic diseases, such as systemic lupus erythematosus, rheumatoid arthritis, and myositis; or with neoplasia. They also may be idiopathic. In some animals, the gammopathy may appear initially to be monoclonal because of the predominance of a single immunoglobulin class (usually IgG). This has been seen in cats with noneffusive feline infectious peritonitis and in dogs with chronic tropical canine pancytopenia.
Monoclonal gammopathies are characterized by the production of large amounts of a single immunoglobulin protein. Monoclonal gammopathies are either benign (ie, associated with no underlying disease), or associated with immunoglobulin-secreting tumors.
Tumors that secrete monoclonal antibodies originate either from plasma cells (myeloma) or lymphoblasts (lymphosarcoma). Plasma-cell myelomas can secrete intact proteins of any immunoglobulin class or immunoglobulin subunits (light chains or heavy chains). Myeloma proteins in dogs are commonly IgG or IgA and less commonly IgM. Myelomas of the IgA type are particularly common in Doberman Pinschers. Monoclonal immunoglobulins produced by lymphosarcoma cells are often of the IgM class, regardless of species. Myeloma proteins in cats and horses usually are IgG and, uncommonly, IgM, IgG3 (horses), or IgA.
Clinical signs depend on the location and severity of the primary neoplasm and on the amount and type of immunoglobulin secreted. Plasma-cell myelomas frequently develop in marrow cavities of flat bones of the skull, ribs, and pelvis, and in the vertebrae. Pathologic fractures of diseased bone can lead to spinal disorders, pain, and lameness.
Clinically evident illness can result from the presence of the monoclonal protein itself. For example, some forms of amyloidosis (see Amyloidosis) are due to deposition of immunoglobulin light chains in tissues (SAA amyloid). Hyperviscosity syndrome occurs in 20% of dogs with IgM or IgA monoclonal proteins if the protein levels in blood are high. In this syndrome, plasma viscosity can be many times normal, resulting in profound vascular disturbances, thrombosis, and bleeding diathesis. Depression, blindness, and neurologic manifestations can be due to hemorrhage in the nervous system and retina. Some IgM monoclonal proteins act as cryoglobulins and aggregate in vitro and in vivo when the plasma is cooled. Animals with cryoglobulinemia often develop gangrenous sloughs of the ear tips, eyelids, digits, and tip of the tail, especially during cold weather. Animals with monoclonal gammopathies may have depressed levels of normal immunoglobulins and, therefore, may develop secondary infections.
Immunoglobulin-secreting tumors usually are treated with appropriate chemotherapy. Plasmapheresis may be needed to lower serum viscosity in animals with clinical signs of hyperviscosity syndrome.
Last full review/revision July 2011 by Ian Tizard, BVMS, PhD, DACVM