Gammopathies

Gammopathy is a term used to describe abnormal levels or forms of gamma globulins, mainly immunoglobulins produced by B lymphocytes. The abnormality can be polyclonal, reflecting broad immune stimulation with multiple immunoglobulin species, or monoclonal, arising from a single clone that produces one type of immunoglobulin or light chain. Gammopathies are often first identified on laboratory studies such as serum protein electrophoresis (SPEP), which may reveal an M-spike in monoclonal conditions; immunofixation (IFE) characterizes the immunoglobulin type, and free light chain assays quantify kappa and lambda chains and their ratio.

Monoclonal gammopathies involve a clonal expansion of plasma cells or B cells and include conditions such as monoclonal gammopathy of undetermined significance (MGUS), smoldering and active multiple myeloma, Waldenström macroglobulinemia, and light chain amyloidosis. MGUS is common in adults and usually asymptomatic, but it carries a risk of progression to a malignant plasma cell or lymphoid disorder. Risk assessment uses factors including the M-protein level, abnormal light-chain ratio, and bone marrow plasma cell percentage.

Polyclonal gammopathies result from generalized immune activation due to infections, autoimmune diseases, chronic liver disease, or inflammatory states. They typically reflect polyclonal increases in diverse immunoglobulin populations rather than a single clone.

Management depends on the underlying condition and its risk of progression. Monoclonal gammopathies may require monitoring or targeted therapy for malignancy, while polyclonal gammopathies focus on treating the contributing inflammatory or infectious process. Regular follow-up with laboratory testing guides clinical decisions.