Interpretation of Freelite® Results

Freelite® is a Sensitive, Specific Marker of Kappa and Lambda Free Light Chains in Serum

 

 

Freelite® results should be considered under the following categories and investigated appropriately.
 
  1. Normal samples. Serum κ, λ and κ/λ ratio are all within the normal ranges. If accompanying serum electrophoretic tests are normal it is most unlikely that the patient has a monoclonal gammopathy.
  2. Abnormal κ/λ ratios. Support the diagnosis of a monoclonal gammopathy and require further investigation. Borderline elevated κ/λ ratios occur with renal impairment and may require appropriate renal function tests.
  3. Low concentrations of κ, λ or both. Indicate bone marrow function impairment.
  4. Elevated concentrations of both κ and λ with a normal κ/λ ratio. May be due to the following:
    · Renal impairment (common)
    · Over-production of polyclonal FLCs from inflammatory conditions (common)
    · Biclonal gammopathies of different FLC types (rare)
  5. Elevated concentrations of both κ and λ with an abnormal κ/λ ratio. Suggest a combination of monoclonal gammopathy and renal impairment.
Classification of monoclonal gammopathies according to serum kappa and lambda concentrations. Sectors refer to areas of the kappa / lambda plotter (see below).

 

Sector
Kappa
Lambda
κ/λ Ratio
Interpretation
1
Normal
Normal
Normal
Normal Serum
2
Low
Low
Normal
BM suppression without Monoclonal Gammopathy
3
High
Monoclonal Gammopathy with BM Suppression
4
Low
5
Normal
Normal
Normal Serum with BM Suppression
6
Low
Monoclonal Gammopathy with BM Suppression
7
High
Low
8
Normal
Low
High
9
Normal
Normal Serum with BM Suppression
10
Normal
High
Monoclonal Gammopathy with BM Suppression
11
Low
12
High
Normal
Polyclonal Ig increase or renal impairment
13
Low
Monoclonal Gammopathy without BM Suppression
14
High
Low
High
Monoclonal Gammopathy with BM Suppression
15
Normal
High
Monoclonal Gammopathy without BM Suppression
16
Normal
Polyclonal Ig increase or renal impairment
17
High
Normal
18
High
Monoclonal Gammopathy with renal impairment
19
Low
BM =
Bone marrow

Serum κ and λ FLC concentrations in a selection of clinical conditions. Normal ranges for κ, λ (and κ/λ ratio - diagonal lines) are shown. Diagonal lines separate monoclonal from polyclonal FLC production. Sector numbers refer to the classification of monoclonal gammopathies according to serum kappa and lambda concentrations. Plot your patient's result using our Kappa/Lambda plotter •

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The most extensive serum free light chain normal range study has been conducted at Mayo Clinic, USA, using Binding Site Freelite® assays for the BN™II2. In this study serum samples from 287 normal subjects aged from 20 to 90 years were assayed for free kappa and free lambda. The results from this trial are shown in the table below.

Normal Adult Serum
Mean Concentration
Median Concentration
95 Percentile Range
Free Kappa
8.36 (mg/L)
7.30 (mg/L)
3.30-19.40 (mg/L)
Free Lambda
13.43 (mg/L)
12.40 (mg/L)
5.71-26.30 (mg/L)
 
Mean
Median
Total Range
Kappa/Lambda ratio*
0.63
0.60
0.26-1.65

 

* In patients with renal failure you may wish to use the published renal reference range; κ/λ ratio 0.37 - 3.1 (instead of 0.26 - 1.65)3.

  

The combination of individual concentrations of the free light chains and their ratio distinguishes a monoclonal increase from excess polyclonal production and renal dysfunction.
The ratio of kappa to lambda in serum is the opposite of that seen in urine, with kappa being lower than lambda. This is despite the fact that there are approximately twice as many kappa producing plasma cells as lambda producing cells.


The explanation for this is kappa molecules (25kDa), that are normally present in serum as monomers, are filtered through the kidney at approximately three times the rate of the lambda molecules (50kDa) which are present as dimers. So although the production rate of lambda in normal patients is lower than kappa, the serum concentration of lambda is actually higher, due to slower renal clearance. This also explains why, in the urine, the reverse is seen with kappa being present at approximately twice the level of lambda.

 

1.     Freelite® Pocket Guide (English International, Non-USA)
2.     Katzmann JA et al.Serum Reference Intervals And Diagnostic Ranges For Free κ And Free λ Immunoglobulin Light Chains: Relative Sensitivity For Detection Of Monoclonal Light Chains Clin Chem 2002;48:9:1437-1444
3.     Hutchison C.A. et al.Serum free light chain measurement aids the diagnosis of myeloma in patients with severe renal failure. BMC Nephrology 2008;9:11 doi: 10.1186/1471-2369-9-11
Download the article here. This is a free access article, please review the copyright statement on the article front page http://www.biomedcentral.com/1471-2369/9/11