FLC Serum

[Presto51]

So I just got back my Free Light Chain Serum results and honestly, I can't figure out what this means.

Kappa FLC, serum 20.84 (High)

Lambda FLC - 7.89 (normal)

Kappa/Lambda FLC Ratio - 2.64 (High)

Also had SPEP + IFE Reflex done - can't figure out what this means either.

All is normal except Gamma Globulin is low at .67

Any help would be appreciated!

[Presto51]

Forgot one last one! Immunofixation 1 says "IgG Kappa (Gamma Region), I've tried to figure out some of this information, but it seems a bit over my head. Thanks in advance!

[gardening-girl in reply to Presto51]

Complimenting  AussieNeil 's excellent explanation, to learn more about serum protein electrophoresis check out the reference below that has a couple of figures showing the electrophoretic separation of albumin and the globulins (alpha1, alpha2, beta and gamma), as well as a sketch of an immunoglobulin molecule showing the heavy (larger) and light (smaller) chains.

Making sense of serum protein bands

bpac.org.nz/bt/2011/july/se...

I've slightly edited Figure 1 of the paper to identify the Gamma region. Following electrophoresis (SPEP) to separate the light chains, anti-kappa and anti-lambda antibodies are used in a process called, immunofixation to determine whether the monoclonal light chain peak is kappa or lambda. The SPEP + immunofixation is called immunofixation electrophoresis (IFE). Does that help you understand?

Serum protein electrophoresis to identify a monoclonal serum light chain

[Presto51 in reply to gardening-girl]

Trying to add up all the different other prognostic factors in this is so confusing. I know I have so many good markers, and a couple not so good, it becomes difficult to know which ones are more important than others and what it means in the big scheme of things. I am positive about everything, but also want to be realistic. I feel as though I need to get a degree in hematology!

[gardening-girl in reply to Presto51]

Presto51, I totally understand. When I received my diagnosis in 1997, I immediately signed a massive hematology text book out of the library! Now I mostly use PubMed for references. I agree with Neil's statement that "you can safely ignore any survival statistics from study papers about these markers."

[AussieNeil Administrator]

B cells develop B cell receptors to detect antigens on viruses, bacteria, fungi and other invaders. These receptors incorporate an immunoglobulin as the sensing part of their structure, which is how they are stimulated to divide in response to an infection. (It's the long lived circulating memory B cells which result from a past infection or vaccination that provides you with long term adaptive immunity,) B cells produce the free floating antibodies/immunoglobulins (proteins) when they mature into plasma cells.

There's roughly a 50:50 chance of either a kappa or lambda light chain being used to make an immunoglobulin. This happens during what's termed somatic hypermutation - the re-arrangement of the B cell IGHV gene in the B cell DNA to produce a successful few of the billions of antibody combinations that can lock onto identifying parts of a bug (or dead parts of a virus, bacteria etc in a vaccine for that matter). With CLL, some of those immunoglobulin light chain proteins (roughly half the time) can be detected in your blood as free light chains (FLC) which are either kappa or lambda. When there's no significant presence of monoclonal (that is cancerous) B cells, this FLC blood test will report somewhere close to a 50:50 ratio due to the randomness of the DNA rearrangement process as each B cell matures and goes through somatic hypermutation. When we have CLL, because the CLL cells produce either a kappa or lambda free light chain immunoglobulin, the Kappa/Lambda FLC Ratio will be either high or low, depending on which type of immunoglobulin (kappa or lambda) is being produced in the CLL cell receptors.

Your CLL incorporates kappa light chains, hence your high Kappa FLC, serum result and your high Kappa/Lambda FLC Ratio.

The FLC serum level was studied about 10 years ago as a possible prognostic marker, thus: ""It has recently been shown that sFLC (serum Free light Chain) and their sum above 60.6 mg/L may contribute usefully to prognosis [15], mainly with regard to TFT." (Time to First Treatment)

ncbi.nlm.nih.gov/pmc/articl... So your sFLC is high, but much lower than this paper found to be useful for Time to First Treatment prediction.

Serum protein electrophoresis (SPEP) or sometimes SEPP, is another prognostic marker test labtestsonline.org/understa...

Please keep utmost in mind that the study of these prognostic markers was before we had the targeted therapy breakthroughs, so you can safely ignore any survival statistics from study papers about these markers.

Neil

[Presto51]

Thank you Neil! I do try to make a point in not getting myself too worked up about every test. It's just amazing how many tests can be done on blood and the breakdown of what each test does can be so confusing and overwhelming! Thank you for taking the time to answer my question!!

[Skyshark]

Lambda, Kappa and the FLC ratio Kappa/Lambda.

12 years ago absolute Kappa+Lambda > 60 and FLCr were quite exciting prognostic indicators for CLL. Not so bothered these days, for many like you it will be W&W with "consider discussion with haematology". Monitoring W&W ends when it becomes "Suggest discuss with haematology." or "urgent referral".

yorkhospitals.nhs.uk/seecms...

Last November I was Lambda very high 236, FLCr very low 0.09 (= Kappa elevated 21.2). Now at cycle 8 of V+O I'm upside down, Kappa normal 15.0, FLCr high 1.78 (= Lambda normal 8.42). For a few weeks around cycle 5, I was "normal" for Kappa, Lambda and FLCr. Whatever was responsible for very high Lambda chains has responded to V+O, while the Kappa chains are only slightly reduced to normal. Other people like you may have a CLL clone that kicks out more Kappa chains instead.

There's nothing you can do about them, let the doctors worry.