Immunoglobulin G (IgG) Heavy and Light Chain (HLC) Pairs, ? and ? With Ratio

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CPT Code:


Test Type: 0.75 mL Serum
Stability Time:



Room temperature

14 days


14 days


14 days

Freeze/thaw cycles

Stable x3

Reference Range:

• IgG κ (g/L): 4.03−9.78

• IgG λ (g/L): 1.97−5.71

• IgG κ:IgG λ ratio: 0.98−2.75

An elevated IgG heavy and light chain (HLC) pair ratio suggests a clonal proliferation of an IgG κ clone of plasma cells.

A low IgG HLC pair ratio suggests a clonal proliferation of an IgG λ clone of plasma cells.


For the quantitative measurement of human IgG heavy chain and light chain intact immunoglobulin in serum. The IgG HLC ratio can be used when monitoring previously diagnosed IgG multiple myeloma in conjunction with other laboratory tests and clinical evaluations.

Heavy and light chain pair quantitation may be useful for:

1. Distinguishing between broadly migrating monoclonal proteins and restricted polyclonal immunoglobulin patterns on serum protein electrophoresis.

2. Quantitating monoclonal IgG proteins that are difficult to quantitate using serum protein electrophoresis alone.

3. Providing a more specific quantitation of the monoclonal protein than total IgG measurements alone.

Decisions on patient evaluation and management must not be given on the basis of IgG κ, IgG λ, or IgG κ:IgG λ ratio measurements alone. Clinical history and other laboratory findings must be taken into account.

Heavy and light chain (HLC) quantitation should be used as a complementary method to serum protein electrophoresis.

The effect of therapeutic drugs on the measurement of IgG κ and IgG λ by this assay has not been evaluated.

Small increases in the concentrations of monoclonal IgG proteins may not result in an altered HLC pair ratio.

Elevated serum concentrations of monoclonal protein are indicative of an underlying abnormality, such as monoclonal gammopathy of undetermined significance (MGUS), multiple myeloma, and other lymphoproliferative disorders. International guidelines recommend serum protein electrophoresis or nephelometric immunoglobulin quantification as tools to monitor patients' disease1 (alongside other tests including flow cytometry and serum free light chain analysis).2 Total IgG nephelometric assays will include nontumor immunoglobulin, and measurement of either IgG κ or IgG λ may give a more accurate representation of tumor production.

Furthermore, measurement of both IgG κ and IgG λ, calculation of the IgG κ:IgG λ ratio, and comparison with values found in normal subjects can give a more sensitive indication of clonality.3-5 Additionally, changes in the IgG κ:IgG λ ratio and its normalization when compared to a normal ratio range should assist in monitoring patients' disease. Use of the IgG κ:IgG λ ratio will also compensate for any changes in plasma volume and correct for half life variations due to receptor saturation.

1. Dimopoulos M, Kyle R, Fermand JP, et al. Consensus recommendations for standard investigative workup: Report of the International Myeloma Workshop Consensus Panel 3. Blood. 2011 May 5; 117(18):4701-4705. PubMed 21292778

2. Rajkumar SV, Harousseau JL, Durie B, et al. Concensus recommendations for the uniform reporting of clinical trials: Report of the International Myeloma Workshop Consensus Panel 1. Blood. 2011 May 5; 117(18):4691-4695. PubMed 21292775

3. Bradwell AR, Harding SJ, Fourrier NJ, et al. Assessment of monoclonal gammopathies by nephelometric measurement of individual immunoglobulin kappa/lambda ratios. Clin. Chem. 2009 Sep; 55(9):1646-1655. PubMed 19617289

4. Ludwig H, Milosavljevic D, Zojer N, et al. Immunoglobulin heavy/light chain ratios improve paraprotein detection and monitoring, identify residual disease and correlate with survival in multiple myeloma patients. Leukemia. 2013 Jan; 27(1):213-219. PubMed 22955329

5. Bradwell A, Harding S, Fourrier N, et al. Prognostic utility of intact immunoglobulin Ig'κ/Ig'λ ratios in multiple myeloma patients. Leukemia. 2013 Jan; 27(1):202-207. PubMed 22699454

Collection Details:

Patient Preparation:

Patient should be fasting for eight hours to avoid lipemic sample interference.

Collection Instructions:

Red-top tube or gel-barrier tube.

Separate serum immediately after coagulation (30 minutes) to prevent hemolysis.