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 result from chronic stimulation of the immune system. They can therefore be caused by:
chronic viral, bacterial, or fungal infections
granulomatous bacterial diseases
chronic parasitic infections
chronic rickettsial diseases, such as tropical canine pancytopenia
chronic immunologic diseases, such as systemic lupus erythematosus, rheumatoid arthritis, and myositis
In many cases, there is no obvious predisposing cause. In some animals, the gammopathy may initially 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 more commonly, associated with immunoglobulin-secreting tumors.
Tumors that secrete monoclonal antibodies originate from plasma cells (myelomas). 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. 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 and cause severe bone erosion. Pathologic fractures of diseased bone can lead to spinal pain and lameness.
Disease can result from the presence of the monoclonal protein itself. For example, some forms of 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. Depression, blindness, and neurologic manifestations can be due to hemorrhage in the nervous system and retina.
Some IgM monoclonal proteins are 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 are therefore immunodeficient.
Immunoglobulin-secreting tumors usually are treated with appropriate chemotherapy. Plasmapheresis may be required to lower serum viscosity in animals with clinical signs of hyperviscosity syndrome.