The idea behind the constitution of Study Groups on the “Bence Jones proteins and Free Light Chains” subject arose on verifying the clinical-diagnosis importance of determining Bence Jones Proteinuria (BJP) lacked adequate standardization of methods, study protocols and reference samples, or even for reporting on results.
Regarding determination of the Bence Jones Proteins, and more generally of the Free Light Chains in urine, the work of the Study Groups has aimed to:
- verify the different operational strategies existent
- evidence and document the analytical problems
then from here, respecting particular realities and demands at all times, verify the possibility of standardizing for the BJP:
- interpretation of results
- reporting the results
As to standardizing the determination of the Bence Jones Proteins, the Study Groups established from the beginning tha the first step and non-negotiable objective is for a sample to result, “BJP-Positive” or “BJP-Negative” in all laboratories dispensing with the method or protocol (i.e. all the first level and in-depth methods) used.
The strategy agreed and adopted by the Study Groups is based on:
- comparing operational experiences of real day-to-day routine of laboratories with diversified dimensions, structures and organizations
- starting with the verification and definition of the “real characteristics” of usable techniques and methods in practice
The work methodology is defined in the following phases:
- experimental phase, comprising multicentric assessment of samples with agreed and known characteristics
- information of participants phase on all the results obtained and preparation of said results
- holding round table “co-ordination meetings” to:
- discuss together the results of the experimental work performed
- individualization, based on consensus, of conclusions and objectives reached, likewise eventual corrective actions to be taken both within the group and those considered convenient to propose outside
- define work to be performed with a view to the following meeting
The “starting point” has been verification and definition of the “real characteristics” of usable techniques and methods in practice.
Therefore, it has been deemed necessary prior to doing anything else, to: assess the “sensitivity” and “accuracy” of each method both intra and inter-laboratory, and thus, with sufficient judgement elements, be able to set them within the BJP search and study strategy.
The first model
For the first verification of methods sensitivity and accuracy the elemental, but linear, model has been taken comprising scaling dilutions of urine samples with important BJP and merely traces of other proteins.
This kind of model enables assessment and comparison of the method sensitivity and accuracy in evidencing “sample abnormality” ignoring considerations about the absolute concentration and the specific characteristics of the BJP.
The results today – the proposal
Since the Study Groups started in 1993, they have carried out experiments and held meetings leading to a significant advance by the participants in the standardization of the BJP determination.
Furthermore, interesting results and conclusions have emerged, some really unpredictable and disconcerting because they were unexpected, regarding the real “sensitivity” and “accuracy” of commercial methods.
The Study Groups reflections on results and work methodology have:
- confirmed the good quality of the strategy and procedures followed,
- enabled formulation of operational proposals and recommendations,
- suggested continuing along the path started not only to improve and complete the proposal, but also to have the results obtained under control,
- induced expanding the experiment horizon on applying the same strategy to the study of proteinuria in general. The objective here is also to verify and improve standardization by comparing the separative traditional methods (Electrophoresis, SDS, etc.) with dosing some specific proteins (so-called “Proteinuria markers”) aided by software used to interpret results and prepare the report.