Robust Reference Intervals for Serum Kappa and Lambda Free Light Chains from a Multi Centre Study Population from Hyderabad, India: Myeloma Diagnostic Implications

  • Mohammed, Noorjahan (Institute of Medical Sciences) ;
  • Chandran, Priscilla Abraham (Institute of Medical Sciences) ;
  • Kandregula, Madhavi (Institute of Medical Sciences) ;
  • Mattaparthi, Ratna Deepika (Institute of Medical Sciences) ;
  • Gundeti, Sadasivudu (Department of Medical Oncology, Nizam's Institute of Medical Sciences) ;
  • Volturi, Jyotsna (Department of Laboratory Medicine, Basavatarakam IndoAmerican Cancer Hospital and Research Institute) ;
  • Darapuneni, Radhika (Department of Lab Medicine, Krishna Institute of Medical Sciences, Omega Hospitals) ;
  • Raju, Sree Bhushan (Department of Nephrology, Nizam's Institute of Medical Sciences) ;
  • Dattatreya, Palanki Satya (Oncology, Omega Hospitals)
  • Published : 2016.05.01


The International Myeloma Working Group considers the serum free light chain (SFLC) assay to be an adjunct to traditional tests. Apart from the FLC ratio, the absolute values of individual free light chains also are gaining importance as they appear to be more relevant in certain clinical settings. Automated assays are available for their determination. As laboratories put new test systems into use catering to different disease populations, they are required by accreditation and certification bodies to verify or establish performance specifications, including reference intervals (RIs) representative of their population. Our aim was to establish local RIs for SFLC in a multicentre representative healthy population using a robust method. There was no significant relationship between SFLC levels and age, gender and creatinine levels. The 95% RI for ${\kappa}SFLC$ was 4.81 to 33.86mg/L, for ${\lambda}$ SFLC was 5.19 to 23.67mg/L and for ${\kappa}/{\lambda}SFLC$ was 0.36 to 2.33, significantly higher than the values given by the manufacturer. The ${\kappa}/{\lambda}$ SFLC ratio at 2.23, covering 100% of the data, showed 72% sensitivity (95% CI=39.0 - 94.0), 100% specificity (95% CI=71.5 - 100.0), 100% PPV (95% CI=21.5 - 100.0), 95% NPV (95% CI=75.4 - 99.9), and 79% accuracy (95% CI=56.0 - 93.0). In the patient group, kit RI for ${\kappa}/{\lambda}$ SFLC ratio classified 45.5% (n=5) as positive vs 9.1% (n=1) positive by the study RI, while the kit RI for kappa FLC classified 90.9% (n=10) as positive vs 54.5% (n=6), indicating increased probability of false positive test results with the kit RI when applied to our patient population. Appropriate and specific reference intervals and criteria values result in fewer false-positive and false-negative results which means fewer wrong or missed diagnoses.


Robust reference intervals;serum;free kappa light chains;free lambda light chains;myeloma


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