Preface to 1st edition 2003

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Preface to 1st edition 2003

Imagine the scene in a darkened room of an immunology laboratory. Four people, a professor, a junior doctor, a medical student and a technician are reviewing gels over a light-box. They are struggling to ascertain which of the serum electrophoresis tests were normal and which would need immunofixation:

Slightly irritated, the elderly, white-haired professor studied the gels again.

"Can you see that small band in the gamma region?" asked the junior doctor.

"Pass me my other glasses," the professor demanded of the technician.

Carefully adjusting his bifocals, he set the line between the two lenses onto the gamma region of the gel, and guessed at the location of the band. In his youth he could see bands as well as anyone - even better.

"Yes, I can clearly see the band now," he stated emphatically.

The young medical student was not so certain and enjoyed provoking the professor.

"I think there might be two bands," she suggested, in a teasing manner, but received a warning elbow nudge from the junior doctor.

He was looking for promotion. He liked the old man and was trying to impress him. Furthermore, he had already seen the results of the serum free light chain tests that showed 625mg/L of free kappa and 5 mg/L of free lambda with a free kappa/lambda ratio of 125.

"We could test for serum free light chains" he suggested cautiously.

"I'm not using those new-fangled methods. A urine test will be fine. What was good enough for Henry Bence Jones is good enough for me," the professor resolutely replied.

The opportunity to develop and evaluate important, new clinical assays occurs rarely. Over a five-year period, we gradually realised that serum assays for immunoglobulin free light chains were both technically feasible and clinically important. Initial results from Birmingham showed that the assays could detect free light chains in serum from patients with light chain multiple myeloma, nonsecretory multiple myeloma and AL amyloidosis that hitherto had no detectable serum abnormalities. These results were confirmed in studies from the Mayo Clinic in Rochester, the National Amyloidosis Centre at the Royal Free Hospital in London, and elsewhere.

It has since been shown that serum free light chain measurements can be used to detect and monitor over 95% of all types of patients with myeloma and AL amyloidosis. Furthermore, serum concentrations provide a more accurate marker of variations in disease than urine measurements. The convenience of serum and the enhanced sensitivity and precision of the free light chain immunoassays suggest that urinalysis may rarely be required. Further studies should also allow a re-evaluation of the existing guidelines for assessment of myeloma. Many questions however, remain unanswered:

• Are serum free light chain assays useful for assessing early responses to chemotherapy?
• Are they an early marker of relapse?
• How sensitive are they for assessing minimal residual disease?.
• Are they a prognostic marker in MGUS?

Present observations also need to be checked and confirmed by other laboratories. Until such time as their full clinical role is determined, it seemed opportune to review historical, analytical and clinical aspects of free light chain assays to both stimulate and substantiate this evolving subject.