Aggregation of Serum Free Light Chains (FLC) Causes Overestimation of FLC Nephelometric Results as Compared to Serum Protein Electrophoresis (SPE) While Preserving Clinical Usefulness.
Bibliographic record
Abstract
Abstract Multiple myeloma is a disease characterised by the overproduction of monoclonal proteins. Whilst concentration of FLC correlates poorly with tumour burden at diagnosis, changes during treatment are considered to be an accurate and sensitive measure of response. Aggregation of FLC presents a problem for traditional means of FLC estimation, large aggregates will not pass through the kidney making urine unreliable. Objectives : To report follow-up of 2 patients with discrepancy between SPE M-spike and serum FLC, one with serum free lambda, the other with serum free kappa. To analyze and confirm presence of multimer FLC aggregates in these 2 patients. Methods : Routine SPE and immunofixation were performed by capillary electrophoresis (CZE). Serum FLC was measured by nephelometry. FLC polymerisation studies were undertaken by SDS-PAGE, Western blot and Sephadex S-200 gel filtration chromatography. Results: First patient (free lambda) is a 80 y woman with IgA lambda multiple myeloma. Upon treatment, IgA lambda peak fell from 18 g/L down to < 0,4 g/L with a serum free lambda remaining at 10 700 g/L. Monoclonal free lambda peak at CZE was estimated to 1,5 g/L, a 7x discrepancy. High dose Decadron therapy was unsuccessful, serum free lambda remaining about 2500 to 4000 g/L for the next 6 months. Polymerisation studies revealed multiple aggregates of FLC with molecular weight (MW) ranging from 24 000 Da to > 200 000 Da. Second patient (free kappa) is a 70 y old man followed since 1985 for an IgG kappa indolent multiple myeloma. Treatment with melphalan in 1998 caused disappearance of M-spike at SPE and persistant hypogammaglobulinemia. Introduction of FLC testing in August 2006 revealed an unexpected serum free kappa of 2740 g/L which remained stable in the following months. This serum free kappa is not visible by CZE. Polymerisation studies revealed multiple aggregates of FLC with MW ranging from 24 000 Da to > 200 000 Da. Conclusion : Serum FLC measurement is a new biological parameter for investigation and follow-up of monoclonal gammopathies with added value as showed here for 2 myeloma treated patients. One should be aware of well known interferences in FLC measurement such as renal dysfunction and polyclonal hyper-gammaglobulinemia. Here we demonstrated a less well documented confounding factor creating an unexpected discrepancy between this nephelometric technique and traditional CZE/SPE. We showed highly overestimated FLC by nephelometry. We revealed a profile of multiple complexes in 2 cases of FLC (one free lambda and one free kappa) of molecular weight up to > 200 000 Da. These multimers may well impact kidney function and interfere with standard urine investigation. It appears clear to us that an interpretation from an experienced professional should accompany any FLC measurement.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.004 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".