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e10 Part XIII Consultative Hematology
Immunoglobulin M
Summary points • Important component of adaptive humoral immune response as initial antibody type produced after antigen exposure
• Measurement of antigen-specific IgM and IgG can be useful in the diagnosis of recent or previous infection
• Most common monoclonal immunoglobulin subtype elevated in Waldenström macroglobulinemia; associated with
hyperviscosity syndrome
Methodology Nephelometry
Specimen requirements Plain or serum separator tube
Indications Suspected immune deficiency, monoclonal gammopathy, assess response to immunization or recent or previous infection
when antigen-specific IgM and IgG are tested
Reference range Table 162.25
Interpretation • Elevated in polyclonal hypergammaglobulinemia, chronic liver disease, collagen vascular disease, autoimmune disease,
some infections, some immune deficiencies, monoclonal gammopathy (lymphoplasmacytic lymphoma and Waldenström
macroglobulinemia), cryoglobulinemia
• Decreases in immune deficiencies, hypogammaglobulinemia, chronic protein loss (protein-losing enteropathy,
malnutrition), some malignancies
• Reference intervals may vary with methodology and patient ethnicity
Related tests IgG, IgA, lymphocyte subsets, serum protein electrophoresis with immunofixation
Interfering substances Lipemia, other causes of severe turbidity, microbial contamination
Ig, Immunoglobulin.
Immunoglobulin Light Chains
Summary points • Measurement of free light chains is done for diagnosis and monitoring of amyloid, nonsecretory myeloma, and light
chain myeloma
• Kappa/lambda ratio is critical—excess of kappa versus lambda or excess of lambda versus kappa light chains is
consistent with a plasma cell dyscrasia
Methodology Nephelometry
Specimen requirements Plain or serum separator tube
Indications Suspected monoclonal gammopathy, amyloidosis, other plasma cell dyscrasia
Reference range Table 162.26
Interpretation Elevated free light chain with either kappa or lambda light chain restriction consistent with amyloidosis or another plasma
cell dyscrasia
Related tests Urine free light chains, urine protein electrophoresis with immunofixation, serum protein electrophoresis with
immunofixation, serum immunoglobulin levels (IgG, IgA, IgM)
Interfering substances Lipemia, other causes of severe turbidity, microbial contamination
Comments May be more sensitive than serum protein electrophoresis with immunofixation for diagnosis of light chain disease
Ig, Immunoglobulin.
Complement Fractions C3 and C4
Summary points • Used to measure complement activation or deficiency
• C3 and C4, measured together, examine both classical and alternative complement pathways
Methodology Nephelometry, quantitative immunoturbidimetric, radioimmunodiffusion, electroimmunodiffusion
Specimen requirements Plain or serum separator tube
Indications Measure activity in collagen vascular diseases (systemic lupus erythematosus), complement deficiency, immune complex
disease, glomerulonephritis, hereditary angioedema
Reference range Table 162.27
Interpretation • Reduced C4 with or without reduced C3 implies classical pathway activation as seen in lupus, immune complex disease,
hereditary angioedema due to C1 inhibitor deficiency, chronic liver disease
• Reduced C3 with normal C4 implies activation by the alternative pathway (e.g., sepsis)
• Elevated C3 and/or C4 implies an acute-phase response
• Primary deficiency is rare and requires functional assay
Related tests Total complement CH50, C1q inhibitor
Interfering substances Lipemia, microbial contamination
Reference Wen L, Atkinson JP, Giclas PC: Clinical and laboratory evaluation of complement deficiency. J Allergy Clin Immunol
113:585, 2004.

