Dr Sheldon is right to highlight ‘the sticky question of whether we can replace urine investigations for Bence Jones protein (BJP) with a serum FREELITE assay (Ann Clin Biochem 2007;44:503–505).
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We cannot, however, let her misquote our study,
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in the light of which, we adopted serum protein electrophoresis (SPE) and serum free light chains as first-line tests for the investigation of possible B-cell disorders. We did not report ‘a false-negative rate of 20%.’ Urine immunofixation (IFE) identified 15 samples with monoclonal kappa (κ) or lambda (λ) bands, 11 of these had abnormal serum κ/λ ratios. The remaining four had normal serum κ/λ ratios, which we described as potential ‘false-negatives.’ As the text of our paper indicates, closer examination showed that only one of the four was actually a false-negative. Case 1 of these four was followed up because a small monoclonal IgG paraprotein was detected by SPE. We do not consider that to be a false-negative – a false-negative would have led to a missed diagnosis. In this case, SPE identified that further investigations were necessary. The IgG paraprotein has remained at 6 g/L at each annual follow-up with no significant change in the serum κ/λ ratio. Case 2 (urine BJP concentration about 50 mg/L) continued to have positive BJP in follow-up samples and serum IFE showed a small IgG-kappa paraprotein, subsequent bone marrow biopsy and skeletal survey showed no abnormality. We are unable to quantify this band by scanning because of the position in the β-2-globulins; however, the total IgG has remained constant at 12–13 g/L. We consider this to be a false-negative – but whether it is of clinical importance is debatable. Cases 3 and 4 showed negative BJP on follow-up urine samples – with hindsight, as described in our paper,
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Case 3 was a reporting error in the initial sample and Case 4 was transient BJP due to high serum immunoglobulins as a consequence of a chest infection.
It is also important to balance the fact of one in 15 false-negatives (6.7%) with the advantage of excluding a light chain disorder in all patients – we do not believe that Dr Sheldon is right to so lightly dismiss the difficulty of obtaining urine samples.
We also noted the value of a serum free light chain result as an aid to interpreting SPE gels and identifying those samples requiring serum IFE. Small bands hidden in the α-2- or β-globulin regions are easily overlooked – even by well-trained laboratory scientists.
We are not suggesting that free light chain assays will replace SPE and serum IFE but as our data show, they can be used, with SPE, as first-line tests for the investigation of possible B-cell disorders.
