Diseases of Immunoglobulin Overproduction (Gammopathies)

Introduction

The monoclonal gammopathies include those diseases in which there is a proliferation of a single clone of immunoglobulin-forming cells that produce a homogeneous heavy chain, light chain, or complete molecule. The amino acid sequence of the variable (V) regions is fixed, and only one type (? or ?) of light chain is produced. Polyclonal gammopathies result from proliferation of many B cell clones, resulting in a diffuse increase of immunoglobulins.

1. Monoclonal Gammopathy of Uncertain Significance (MGUS)

Introduction

Essentials of Diagnosis

• M protein in the serum without symptoms or signs of multiple myeloma, macroglobulinemia, amyloidosis, or lymphoma.
  
• Less than 10% plasma cells in the bone marrow.

General Considerations

The incidence of MGUS increases with age and may approach 3% in persons 70 years of age or older. Lymphoid malignancies, amyloidosis, or multiple myeloma will develop in as many as one-third of patients with apparently benign monoclonal gammopathies. No specific therapy is necessary, but close observation is required. MGUS patients should be periodically monitored for changes in serum M proteins, urinary Bence-Jones proteins, evidence of renal failure, anemia, hypercalcemia, lytic bone lesions, or bone marrow plasmacytoses. Risk of developing a malignant disorder is 12% at 10 years, 25% at 20 years, and 30% at 25 years. Parameters that suggest a favorable prognosis include (1) concentrations of homogeneous immunoglobulin less than 2 g/dL, (2) no increase in concentration of the immunoglobulin from the time of diagnosis, (3) no decrease in the concentration of normal immunoglobulins, (4) absence of a homogeneous light chain in the urine, and (5) normal hematocrit and serum albumin.

Clinical Findings

A. Symptoms and Signs
No clinical symptoms are associated with MGUS. In patients with MGUS, the quantity of M protein is stable, and the lymphadenopathy, splenomegaly, or bony lesions seen with multiple myeloma are absent.

B. Laboratory Findings
The diagnosis of MGUS is made upon finding of a monoclonal spike on serum protein electrophoresis, confirmed by immunoelectrophoresis to be a homogeneous immunoglobulin with either ? or ? light chains.

Preferences

_{Blade J, Kyle RA: Monoclonal gammopathies of undetermined significance. In: Malpas JS et al (editors). Myeloma: Biology and Management, 2nd ed. Oxford University Press; 1998.}