[Ali1977]

Low kappa FLC & low kappa / lambda FLC ratio

by Ali1977 on Fri Feb 13, 2015 5:46 am

Hello,

I am a 37 year old male. My general health is good. I don't feel anything out of ordinary at this time. I have not been diagnosed with MGUS. However, my GP and I are investigating some irregularities in my blood tests. I would appreciate your opinion about my condition.

A little bit of history: My mother was diagnosed with solitary plasmacytoma in January 2013. She underwent radiotherapy and since then she is being checked every 6 month for possible progression to multiple myeloma. So far it seems she is fine.

As for myself, I was diagnosed with vitiligo in May 2014. At that time, my GP ordered a blood test to check on other autoimmune disorders. Here are the following results:

WBC: 4.6 (4.0-10.0)
RBC: 5.73 (4.20-5.40)
Hemoglobin: 160 (133-165)
Hematocrit: 0.47 (0.38-0.50)
MCV: 82 (82-98)
MCH: 27.9 (27.5-33.5)
MCHC: 342 (305-365)
RDW: 14.1 (11.5-14.5)
Platelet Count: 229 (150-400)

Neutrophils: 2.9 (2.0-7.5)
Lymphocytes: 1.3 (1.0-4.0)
Monocytes: 0.3 (0.1-0.8)
Eosinophils: 0.1 (0.0-0.7)
Basophils: 0.0 (0.0-0.2)
Granulocytes Immature: 0.0 (<0.2)

Ferritin: 88 (15-300)

Glucose Fasting: 4.7 (3.3-5.5)
Creatinine: 87 (70-120)
Estimated GFR: 86 (>=60)

Thyroid Function / TSH: 0.87 (0.27-4.2)

C Reactive Protein (High Sensitivity): 0.5 (<5.0)

Nuclear Ab Titre and Pattern: Neg (Titre <1:80)

Rheumatoid Factor: <14 (<14 kU/L = Negative)

Tissue Transglutaminase Ab IgA: <0.5 Negative (<12.0)

8 month later (January 2015), he ordered another round of blood test as part of my annual check up. This time, the following had changed:

WBC: 3.9 (from 4.6, which was slightly below normal range)
Platelet Count: 221 (from 229)

Neutrophils: 2.4 (from 2.9)
Lymphocytes: 1.3 (same)
Monocytes: 0.2 (from 0.3)
Eosinophils: 0.1 (same)
Basophils: 0.0 (same)
Granulocytes Immature: 0.0 (same)

Ferritin: 117 (from 88)
TSH: 1.2 (from 0.87)
C Reactive Protein (High Sensitivity): 0.8 (from 0.5)

At this time, I checked my previous lab reports and I noticed since 2008 my WBC and Platelet Count have steadily decreased over the years and every year I had a blood test. in 2008, WBC was 5.1 and Platelet Count was 255, and both have decreased every year in every test.

I discussed this with my GP and, considering my mother's health history of solitary plasmacytoma, he ordered a more in depth blood test including free light chain FLC testing. Here are what changed this time since 3 weeks ago:

WBC: 4.9 (from 3.9)
Platelet Count: 221 (same)

Neutrophils: 3.1 (from 2.4)
Lymphocytes: 1.5 (from 1.3)
Monocytes: 0.3 (from 0.2)
Eosinophils: 0.1 (same)
Basophils: 0.0 (same)
Granulocytes Immature: 0.0 (same)

And the extra tests:

Total Protein: 76 (60-80)

Protein Electrophoresis
Albumin: 52.2 (37.0-55.0)
Alpha 1 Globulin: 1.7 (1.0-3.0)
Alpha 2 Globulin: 6.8 (5.0-9.0)
Beta Globulin: 8.1 (5.0-10.0)
Gamma Globulin: 7.1 (5.0-12.5)
Pattern: No paraprotein band is seen on electrophoresis and pattern appears unremarkable.

Light Chains Kappa Free: 2.2 (3.3-19.4)
Light Chains Lambda Free: 10.1 (5.7-26.3)
Light Chains Kappa Free / Light Chains Lambda Free: 0.22 (0.26-1.65)

I visited him today, he said everything looks in the range except the Light Chains Kappa Free, which is well lower than normal range. This has resulted in low ratio of Kappa / Lambda, even though Lambda is in normal range.

He said he is not sure what could be the reason and he has to look into it further and will be in touch with me. He might refer me to a hematologist though.

Considering the above results that seem to be mostly in the normal range (some like the total protein on the upper side of the range though), I was wondering what could be the cause of these abnormalities and specifically the low number of Light Chains Kappa Free number and the ratio.

Can this be normal for me? What would you suggest my next step to be to follow up on this?

Thanks!

[Zan]

Re: Low kappa FLC & low kappa / lambda FLC ratio

by Zan on Sat Feb 14, 2015 6:29 pm

I didn't see immunoglobulin (IgG, IgA, IgM) results in your list. That's what I'd check next.

As for the abnormal serum free light chain ratio, the docs get concerned when it is hugely out of range. For now, it is just something to get checked.

MGUS was a scare for me until I learned how small the chance is for progression; only 1% per year. Now, I just routinely get blood work to keep an eye on it.

[Ali1977]

Re: Low kappa FLC & low kappa / lambda FLC ratio

by Ali1977 on Mon Feb 16, 2015 5:03 pm

Thanks for your response Zan. I will follow up on it and ask my doctor to check immunoglobulin levels.

I also contacted a friend of mine who lives overseas and who specializes in pediatric hematology. Here is his feedback:

You shouldn't worry about your blood result (platelets, white counts), these results are within normal range and fluctuate on daily basis. As far as CRP is concerned, it is a highly sensitive test, and it measures the body's general state of inflammation. So if you have a cold, it goes up, if you have stomach flu, it goes up. Ferritin also tend to follow CRP as they both can increase with slight illnesses. Their level is also mildly higher than normal.

I am not an expert on the light chain proteins, but they are usually used for diseases that produce many proteins (e.g. myeloma) and it could be used to see which type is produced. While the majority of the population typically produces more kappa than lambda, about 15% of individuals produce more lambda than kappa, and I think your results just reflect this fact.

I don't think, based on these results, anyone can give you a diagnosis at this point (unless you have other symptoms)."

[nomm]

Re: Low kappa FLC & low kappa / lambda FLC ratio

by nomm on Mon Feb 16, 2015 8:18 pm

Hi Ali1977.

I don't understand how your doctor may refer you to do something that he does not understand. Something like sFLC.

I think you should do SPEP again, as well as UPEP, immunoglobulins, and B2-microglobulin. These are conservative, but very valid measurements that every doc would do first. You do not have to wait for haematologist to do this and results can put your mind in ease (hopefully).

If this all are negative, the chance that you have MGUS are miserable.

[Ali1977]

Re: Low kappa FLC & low kappa / lambda FLC ratio

by Ali1977 on Mon Feb 16, 2015 10:06 pm

Hi nomm,

Thanks for your response. I will ask my GP to order the tests you mentioned. As you may know, in Canada, we can't visit specialists directly. We must go to a GP first and s/he refers us to a specialist if needed. He did refer me to a hematologist couple of days ago, but I am not sure how long the wait will be until I hear back from the hematologist's office. Not sure why my GP ordered the SFLC and not the other tests. I guess he either expected normal results to assure me I am okay, or the high and out of range of kappa or lambda, which he had seen before in other patients. My guess is that he was caught off guard by the kappa being low and lambda being normal, causing low ratio.

Based on an interpretation chart I found at Wikilite, this might be a case of monoclonal gam­mop­athy with bone marrow suppression, and/or indicate bone marrow function impairment. I will ask the GP to order the test you mentioned while waiting for the hematologist appointment. I'll post an update here. Thanks!

[Toni]

Re: Low kappa FLC & low kappa / lambda FLC ratio

by Toni on Mon Feb 16, 2015 11:27 pm

I would encourage you to follow the advice of your pediatric hema­tol­ogist friend. They are correct in saying that there can be variances in our blood work and, if they are in normal ranges, or very close to it, and you are generally asymptomatic, you may not have anything to further investigate.

My serum free light chain ratio is out of the normal range by what I thought was quite a bit. I had my hematologist explain it to me and it made sense. He said they do pay more attention when it's lower, but, even then, not when it is only slightly lower. And, remember, a hematologist looks at the whole picture of you - not just one test.

Good luck! Unless I missed something, I think your numbers look good.

[nomm]

Re: Low kappa FLC & low kappa / lambda FLC ratio

by nomm on Tue Feb 17, 2015 9:50 am

Hi Ali1977,

I understand your fear. That's why you should insist on your GP to do all these tests now.This way you will have an idea, withing one week max, what is going on in your blood / urine, and bring these results to the haematologist.

I am not an expert, but from my understanding, if something is abnormal, it will show in your urine protein electrophoresis or immunoglobulins results. Since your SPEP is normal, the mentioned above should be checked carefully. Hopefully, everything is normal and then you can do again SFLC and UFLC.

You probably read already that the only case when everything is normal and a person has multiple myeloma is non-secretory myeloma, and it can be measured by light chains and bone marrow biopsy. But every haemotologist will first do the test I have mentioned to you.

So just save your time and stress. Hopefully, you are ok.

[Ali1977]

Re: Low kappa FLC & low kappa / lambda FLC ratio

by Ali1977 on Thu Feb 19, 2015 4:34 am

Thanks nomm!

I have an appointment with my doctor next week. I will ask him to order the extra tests. I am flying to California tomorrow and will be there for few days for work. I will try to visit a hematologist and get his/her opinion too. I might even stay longer and do some of the tests.I have couple of questions, which I could not find answers for them. I appreciate it if anyone could shed some light on these questions:

(1) Do kappa and lambda numbers and ratio change and fluctuate in healthy adult individuals? Do they go up and down or are they always constant in a healthy individual? In case of a healthy adult individual, are the results exactly the same now, 6 month from now and or 5 year from now?

(2) My results were as following:

Light Chains Kappa Free: 2.2 (3.3-19.4)
Light Chains Lambda Free: 10.1 (5.7-26.3)
Light Chains Kappa Free / Light Chains Lambda Free: 0.22 (0.26-1.65)

Obviously Kappa is low and as a result the ratio is low. Based on what I've been reading, this points to plasma cell disorders that produce excess monoclonal lambda light chains (even though lambda is in normal range).

My question is whether its possible for an individual to have such numbers and perhaps such disorder and be healthy. Is it possible that I've had such numbers for many years and continue to have them for many years without any specific illness or reason?

[Toni]

Re: Low kappa FLC & low kappa / lambda FLC ratio

by Toni on Thu Feb 19, 2015 5:42 pm

I'm no doctor, but I'd have to say, I think a lot of folks would love to have your blood test results

Keep in mind that minor fluctuations are common. We even sometimes go a little over or under the "normal" range. Sometimes what's normal for you may be a little under or over.

Most physicians will look at your overall health picture, and not just your lab results. Unless there is something we are missing, you seem to have good health.

What your doctor should check is your SPEP (serum protein electrophoresis) test. This will tell you if you have a monoclonal gammopathy. It seems your concern is that you might develop some­thing akin to your mother's solitary plasmacytoma.

Another poster already recommended this, so I just want to emphasize that the best test to have done is this one. The others will not give you any kind of specifics and the test results you listed look good.

Best of luck and health to you.

[Scott M]

Re: Low kappa FLC & low kappa / lambda FLC ratio

by Scott M on Fri Feb 20, 2015 12:08 pm

Hi Ali1977

Regarding measurement of serum free light chains, there is some variability. See

"Free Light Chains - Serum", Canterbury Health Laboratories - Test Manager

Concerning "Uncertainty of Measurement":

Whilst sensitive, this test is subject to considerable variability, especially if not analysed in the one laboratory (up to 50%). It is therefore strongly recommended that monitoring of a patient be performed through one laboratory and the results of several tests be reviewed to determine the overall picture.”

Some reasons for variability:

J Tate et al, "Quantitative Serum Free Light Chain Assay – Analytical Issues," Clinical Biochemistry Review, Aug 2009 (full text at PubMed)

Assay imprecision determined between reagent lots has a variation of 8–45% for FLC concentrations and 17–32% for the calculated κ/λ FLC ratio. Dilution studies indicate some over-recovery of FLC, which may depend upon the dilution matrix. However, greater discrepancies are underestimation from nonlinear reactions and overestimation possibly from interferences or multi-reactivity to polymeric FLC. Nonlinear monoclonal FLC give concentrations which are 2- to 6-fold increased at higher sample dilution and FLC measured on different platforms may not give the same results.”

D Maisin et al, "Quantification of serum free light chain kappa and lambda by the SPAPLUS analyser," Clinical Biochemistry, 2012 (full text PDF)

Results: Regression analysis between the BNII® and the SPAPLUS® for κ FLC and λ FLC did not display any significant differences between both methods in the normal and pathological ranges. Nevertheless, some differences have been observed for some patients in the absolute value of the involved light chain, with potential clinical implications.”