Abnormal Protein Production in Dogs

Antibodies, white blood cells made up of immunoglobulin protein, normally circulate in the blood as part of the body’s immune system. Sometimes these cells can proliferate abnormally, creating high levels of monoclonal protein or M-components in the blood. This condition is called paraproteinemia or monoclonal gammopathy.  This occurs most commonly in middle-aged or older dogs. It is usually a sign of an immunoglobulin-secreting tumor, most commonly a plasma cell neoplasm such as multiple myeloma, but chronic leukemia and lymphoma can also cause paraproteinemia. These cancers can weaken bones structure, and severely affected dogs may have small fractures in the spine and elsewhere. High levels of M-components can also cause hyperviscosity (increased blood coagulation) which leads to problems with blood clots and bleeding. Paraproteinemia may be related to amyloidosis, a rare disorder that affects protein folding and generates abnormal proteins in the blood and elsewhere. In other cases, paraproteinemia is present without any symptoms or a known cause. This is called monoclonal gammopathy of undetermined significance (MGUS). This is rare in dogs. Although it is a benign condition, MGUS should be monitored closely since it can be a precursor to the development of cancer.

Immunoglobulin is a normal protein that makes up the blood’s disease fighting antibodies. Sometimes these proteins can proliferate abnormally, however, leading to high levels of one type of immunoglobulin in the blood. This is called paraproteinemia. It is usually due to myeloma or another type of blood cancer.

Low levels of paraproteinemia may be non-symptomatic, but severe cases have serious life-threatening symptoms. See a veterinarian immediately if you notice any of the following signs in your dogs.

• Lethargy
• Weakness
• Nosebleed
• Bleeding gums
• Retinal bleeding
• Thirst
• Frequent urination
• Lameness
• Blindness
• Disorientation
• Seizures

Types

The veterinarian may find only one type, or several different types of M-components in the blood. 

• Light chains – a small polypeptide subunit of an antibody, often found with amyloidosis
• Heavy chains – a larger polypeptide subunit of an antibody
• Whole immunoglobulin cells – the entire antibody.

M-components are made up of different types of immunoglobulin protein. Three different proteins can be found in dogs with paraproteinemia.

• IgG – the least serious type, less likely to cause hyperviscosity
• IgA – common in Doberman Pinschers
• IgM - rare

As with most cancer-like conditions, the factors that generate paraproteinemia are not fully understood, so many cases are considered idiopathic. Veterinarians believe these conditions may contribute to your dog developing abnormal protein production.

• Inherited predisposition
• Chronic autoimmune response
• Infections
• Carcinogens

The veterinarian will need to do a full physical examination of your dog. Bloodwork will show the presence of abnormal immunoglobulin proteins. Other abnormalities may also be present with myeloma, including a low red blood cell count (anemia) and a reduction in the number of normal white blood cells. Disorders that are affecting the bone marrow often lead to hypercalcemia because calcium is leached from the bones into the blood. Blood coagulation levels will also need to be evaluated.

Light chains can often be found in the urine where they are called Bence-Jones protein, so the veterinarian might test for this if amyloidosis is suspected. Other tests may determine the type of immunoglobulin protein that is present and also check for infection. Paraproteinemia can weaken the immune system and make dogs more prone to viral or bacterial infections.

With cancerous conditions, the veterinarian will order x-rays to evaluate the state of the bones and check for fractures. A bone marrow biopsy could be needed to determine how deeply the bone marrow is affected. This is an invasive procedure that requires inserting a hollow needle into a bone to obtain a marrow sample. A lymph node biopsy could be necessary to diagnose lymphoma.

Dogs with significant symptoms will be treated supportively. This could include intravenous fluids or blood transfusions if paraprotein levels are very high. Antibiotics may be given to limit infection and support the immune system. Plasmapheresis, the removal of unhealthy plasma cells, could be necessary in severe cases.

Most cancerous conditions, including primary amyloidosis, will be treated with chemotherapy. In dogs, this is usually given via injection. Appointments could be scheduled one or more times per week. Each appointment will last at least an hour and a half for adequate monitoring. The veterinarian will likely re-evaluate your dog in a few weeks, to determine the effectiveness of treatment and decide how long it should be continued. Some dogs may have significant gastrointestinal side-effects with chemotherapy.

If the cause is unknown and your dog is not experiencing other symptoms, the veterinarian may define the condition as MGUS or benign paraproteinemia. In this case treatment will not be necessary, but the veterinarian will still need to monitor your dog regularly.

Unfortunately, most of the conditions causing paraproteinemia don’t have a good chance of recovery. Depending on the severity, some types of cancer may respond to chemotherapy and could remain in remission for a number of months or even years. However they are likely to return and could eventually require euthanasia. Benign forms of paraproteinemia are rare in dogs, but if the condition is not causing a problem, your dog may live with it for many years. The prognosis will be dependent on the diagnosis of a veterinarian.