Serum free light chains among twin siblings: is the kappa/lambda ratio genetically determined?

Abstract

Background

Serum kappa, lambda, the K/λ light chain concentrations are used for screening, diagnosis, and monitoring of patients with multiple myeloma and other plasma cell disorders. Biological variation studies conducted on healthy subjects showed that free light chains have a low within and high between-individual variation. We determined if this variation were genetically linked.

Methods

We obtained a single serum sample from 16 pairs of identical twins, 8 neonate twins, and 19 presumed directly-related siblings children, measured Κ and λ light chains and computed the Κ/λ ratio.

Results

As expected, Κ/λ results from each twin neonate were near identical (reflecting maternal/placental transfer). For older children and adult twins, the Κ/λ ratio form a cluster of results that were a subset of the reference range. There was one outlier, a female with a high, different from her twin sister. She likely had a monoclonal gammopathy (no followup was possible). Excluding this pair, results from neonate twins (14.4% ±10.3%) and non-neonate twins (18.0 ± 15.3%) were not significantly different. Results between non-twin siblings were more scattered (53.2%±53.4%) and different from neonate and non-neonate twin adult and children.

Conclusion

We suggest that the Κ/λ free light chains may be genetically linked.

CLINICAL SIGNIFICANCE

• Measurement of serum free kappa (K) and lambda light (l) chains and the K/L ratio are used to diagnose multiple myeloma and monitoring the disease following treatment.

• In health, the K/L ratio are consistent and occupy a small fraction of the reference range.

• By studying twins, we determined that this ratio is likely genetically determined.

Keywords:

• Kappa and lambda free light chains
• biological variation
• reference ranges

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

All data were stored on the computer of the corresponding author’s main laboratory and can be requested from the corresponding author.

Additional information

Funding

This work was sponsored in part by Diazyme Inc., San Diego, CA.