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 subunits in serum, urine, or both
Патофізіологія
(For structural features and classification of the immunoglobulins, see Antibodies.)
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 in the bone marrow 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 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: M-protein can form fibrillar deposits within organs, most commonly the heart and kidneys.
Osteoporosis, hypercalcemia, 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—for classification, see table 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.
Класифікація захворювань плазматичних клітин
Symptoms | Description | Examples |
|---|---|---|
Monoclonal gammopathy of undetermined significance | ||
Asymptomatic, usually slowly progressive Occurring in apparently healthy people or in those with other conditions | Associated with B-cell cancers but also nonlymphoreticular tumors | B-cell lymphoma, chronic lymphocytic leukemia, multiple myeloma, or, less commonly, carcinomas of the breasts, biliary tree, gastrointestinal tract, kidneys, and prostate |
Associated with chronic inflammatory and infectious conditions | Chronic cholecystitis, osteomyelitis, pyelonephritis, rheumatoid arthritis, tuberculosis | |
Associated with various other disorders | Familial hypercholesterolemia, Gaucher disease, Kaposi sarcoma, lichen myxedematosus, liver disorders, myasthenia gravis, pernicious anemia, hyperthyroidism | |
Malignant plasma cell disorders | ||
Asymptomatic, progressive | Usually intact monoclonal immunoglobulin molecules (IgG, IgA, IgM, IgD) with or without monoclonal light chains (Bence Jones proteins) in urine and/or in serum) | Smoldering multiple myeloma |
Symptomatic, progressive | Excess production of IgM | |
Most often IgG, IgA, or light chains (Bence Jones) only | ||
Usually intact immunoglobulin molecules (IgG, IgA, IgM, IgD) with or without monoclonal light chains (Bence Jones proteins) in urine and/or serum) | ||
Heavy chains | IgG heavy chain disease (sometimes benign) IgD heavy chain disease | |
Transient plasma cell disorders | ||
Not necessarily symptomatic | Associated with drug hypersensitivity, viral infections, and heart or transplant surgery | Hypersensitivity to sulfonamides, phenytoin, or penicillin |
Діагностика
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.
