Plasma cell disorders are a diverse group of disorders of unknown etiology characterized by
Disproportionate proliferation of a single clone of B cells
Presence of a structurally and electrophoretically homogeneous (monoclonal) immunoglobulin or polypeptide subunit in serum, urine, or both
Pathophysiology
(For structural features and classification of the immunoglobulins, see Antibodies Antibodies The immune system consists of cellular components and molecular components that work together to destroy antigens (Ags). (See also Overview of the Immune System.) Acute phase reactants are plasma... read more .)
After developing in the bone marrow, undifferentiated B cells enter peripheral lymphoid tissues, such as the lymph nodes, spleen, and gut (eg, Peyer patches). Here, they begin to differentiate into mature cells, each of which can respond to a limited number of antigens. After encountering the appropriate antigen, some B cells undergo clonal proliferation into plasma cells. Each clonal plasma cell line is committed to synthesizing one specific immunoglobulin antibody that consists of 2 identical heavy chains (gamma [γ], mu [μ], alpha [α], delta [δ], or epsilon [ε]) and 2 identical light chains (kappa [κ] or lambda [λ]). A slight excess of light chains is normally produced, and urinary excretion of small amounts of free polyclonal light chains (≤ 40 mg/24 hours) is normal.
In plasma cell disorders, disproportionate proliferation of one clone results in a corresponding increase in the serum level of its product, the monoclonal immunoglobulin protein (M-protein). M-proteins may consist of both heavy and light chains or of only one type of chain.
Complications of plasma cell proliferation and M-protein production include the following:
Damage to organs (particularly the kidneys due to hypercalcemia Hypercalcemia Hypercalcemia is a total serum calcium concentration > 10.4 mg/dL (> 2.60 mmol/L) or ionized serum calcium > 5.2 mg/dL (> 1.30 mmol/L). Principal causes include hyperparathyroidism... read more or toxic light chains secreted by the malignant plasma cells): Some M-proteins show antibody activity against self-antigens.
Impaired immunity: There is decreased production of other immunoglobulins and impaired T-cell responses.
Bleeding tendency: M-protein may cause bleeding by coating platelets, inactivating clotting factors, increasing blood viscosity, and other mechanisms.
Amyloidosis Amyloidosis Amyloidosis is any of a group of disparate conditions characterized by extracellular deposition of insoluble fibrils composed of misaggregated proteins. These proteins may accumulate locally... read more
: M-protein can form fibrillar deposits within organs, most commonly the heart and kidneys.Osteoporosis Osteoporosis Osteoporosis is a progressive metabolic bone disease that decreases bone mineral density (bone mass per unit volume), with deterioration of bone structure. Skeletal weakness leads to fractures... read more
, hypercalcemia Hypercalcemia Hypercalcemia is a total serum calcium concentration > 10.4 mg/dL (> 2.60 mmol/L) or ionized serum calcium > 5.2 mg/dL (> 1.30 mmol/L). Principal causes include hyperparathyroidism... read more , anemia, or pancytopenia: Clonal cells can infiltrate bone matrix and/or marrow.
Plasma cell disorders can vary from asymptomatic, stable conditions (in which only the monoclonal protein is present) to progressive cancers (eg, multiple myeloma Multiple Myeloma Multiple myeloma is a cancer of plasma cells that produce monoclonal immunoglobulin and invade and destroy adjacent bone tissue. Common manifestations include lytic lesions in bones causing... read more 
—for classification, see table Classification of Plasma Cell Disorders Classification of Plasma Cell Disorders 
). Rarely, transient plasma cell disorders occur in patients with drug hypersensitivity (eg, sulfonamides, phenytoin, penicillin), with presumed viral infections, and after heart or transplant surgery.
Diagnosis
Plasma cell disorders may be suspected because of clinical manifestations most often bone disease, renal failure, and low blood counts, or an incidental finding of elevated serum protein or proteinuria that leads to further evaluation with serum or urine protein electrophoresis. Electrophoresis often detects an M-protein and/or elevated serum free light chains. These findings are further evaluated with immunofixation electrophoresis for identification of heavy and light chain classes.
Drugs Mentioned In This Article
| Drug Name | Select Trade |
|---|---|
phenytoin |
Dilantin, Dilantin Infatabs, Dilantin-125, Phenytek |
