15. Disorders of immunoglobulins and paraproteins
Monoclonal gammopathy
Monoclonal gammopathy refers to any condition where there is excessive amounts of a monoclonal gammaglobulin in the blood, as evidenced by the presence of a tall peak in the gamma band on serum electrophoresis. These monoclonal gammaglobulins are called "M proteins". Monoclonal gammopathy is the opposite of polyclonal gammopathy.
The following are the most common monoclonal gammopathies:
Multiple myeloma
Multiple myeloma (MM), sometimes called plasma cell myeloma, is the most important of the plasma cell dyscrasias. It is characterised by proliferation of genetically abnormal monoclonal plasma cells in the bone marrow, which produce monoclonal paraprotein which leads to organ damage and which can be detected in blood and urine.
It’s the second most common haematological malignancy. It mostly affects elderly. Its prognosis used to be poor but nowadays the expected overall survival is >5 years. However, it is still considered incurable.
Sometimes multiple myeloma presents as a solitary tumour, in which case it’s called plasmacytoma.
Diagnosis and evaluation
Multiple myeloma is diagnosed when the following criteria are met:
- >10% of the bone marrow is monoclonal plasma cells
- Presence of a myeloma-defining event (MDE) according to the CRAB SLiM criteria:
- C – Calcium elevation (hypercalcaemia)
- R – Renal insufficiency
- A – Anaemia (normocytic)
- B – Bone lesions
- S – >60% of the bone marrow is monoclonal plasma cells
- Li – Involved/uninvolved serum free light chain ratio elevated
- M – MRI with >1 focal lesion of bone or bone marrow
Complications
Amyloid light-chain (AL) amyloidosis can occur due to the excessive light-chain production. This can result in cardiomyopathy or kidney disease, among others. Kidney disease can also occur due to excessive filtering of Bence-Jones proteins or due to the effects of hypercalaemia.
Infection is a major cause of death in patients with multiple myeloma, partly due to secondary immunodeficiency due to the high level of non-functional immunoglobulins and partly due to side effects of medications.
Polyclonal gammopathy
Polyclonal gammopathy refers to any condition where there is excessive amounts of polyclonal gammaglobulin in the blood, as evidenced by a wide (but not peaked) gamma band on serum electrophoresis. Polyclonal gammopathy is the opposite of monoclonal gammopathy.
Polyclonal gammopathy is a part of the regular immunologial response to any infection and many forms of inflammation, where B cells produce antibodies (immunoglobulins).