When it comes to diagnosing light chain monoclonal gammopathy of undetermined significance (MGUS), does either kappa or lambda free light chain level have to be above the reference range?
I've got a high kappa / lambda ratio of 2.75, but it's due to a low lambda free light chain level rather than a high kappa level, which is right in the middle of the reference range. Any chance that could be light chain MGUS? Seems like the only other alternative is AL amyloidosis, and I'm hoping against hope that it's not that.
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Re: Light chain MGUS - criteria for diagnosis
I've checked several articles on this subject, and the criteria for a diagnosis of light-chain MGUS are usually described this way:
Also, just to be clear, while your free light chain ratio is above normal, it would rarely be described as "high". It's slightly elevated / above normal, and would even be considered within the normal range for someone with impaired kidney function.
- Abnormal FLC ratio (<0.26 or >1.65)
- Increased level of the appropriate involved light chain (increased kappa FLC in patients with ratio >1.65 and increased lambda FLC in patients with ratio <0.26)
- No immunoglobulin heavy chain expression on immunofixation
- Absence of end-organ damage such as hypercalcemia, renal insufficiency, anemia, and bone lesions (CRAB) or amyloidosis that can be attributed to the plasma cell proliferative disorder
- Clonal bone marrow plasma cells <10%
- Urinary monoclonal protein <500 mg/24 h
Also, just to be clear, while your free light chain ratio is above normal, it would rarely be described as "high". It's slightly elevated / above normal, and would even be considered within the normal range for someone with impaired kidney function.
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JimNY
Re: Light chain MGUS - criteria for diagnosis
I'm so happy to find this question, btdyq5. I have the same question!
JimNY -- I've seen criteria like those you shared and was left wondering what the abnormal ratio means if you end up not having any of the other criteria. Would that mean it's not technically MGUS?
I've had three abnormal ratios due to low lambda and I'm finally going to go to a hematologist. The waiting is tough (appointment August 4)!
April 17: Lambda 2.99, Kappa 9.68, Ratio 3.24
May 11: Lambda 3.72, Kappa 13.73, Ratio 3.69
June 7: Lambda 3.24, Kappa 12.19, Ratio 3.76
Not sure if it's relevant, but I also have low C3 and immunoglobulin A. After living with an undifferentiated autoimmune disease for more than 10 years, I am wondering if these newest blood abnormalities could just be from that.
JimNY -- I've seen criteria like those you shared and was left wondering what the abnormal ratio means if you end up not having any of the other criteria. Would that mean it's not technically MGUS?
I've had three abnormal ratios due to low lambda and I'm finally going to go to a hematologist. The waiting is tough (appointment August 4)!
April 17: Lambda 2.99, Kappa 9.68, Ratio 3.24
May 11: Lambda 3.72, Kappa 13.73, Ratio 3.69
June 7: Lambda 3.24, Kappa 12.19, Ratio 3.76
Not sure if it's relevant, but I also have low C3 and immunoglobulin A. After living with an undifferentiated autoimmune disease for more than 10 years, I am wondering if these newest blood abnormalities could just be from that.
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Anonymous
Re: Light chain MGUS - criteria for diagnosis
To the anonymous poster above: Did you find anything out at your recent appointment? I'm still none the wiser as to what is going on with me.
Re: Light chain MGUS - criteria for diagnosis
Hello there,
I also have similar lab results, and looking for any input anyone can give.
July 5, 2016
Free kappa light chains - 16.7 mg/L (3.3-19.4)
free lambda light chains - 3.7 mg/L (5.7-26.3)
Free kappa/lambda ratio - 4.51 (0.26-1.650)
Total protein- 67 (63-82)
Albumin - 39 (33-48)
Electrophoresis interpretation: Pattern unremarkable
Calcium- 2.12 (2.05-2.55)
GFR- 106, normal creatinine
However, I recently had the blood work repeated and my light chain numbers are now normal:
Oct 21, 2016
Free kappa light chains - 15.8
Free lambda light chains - 9.7
Free kappa/lambda ratio - 1.63
Total protein - 71
Albumin - 36
Electrophoresis interpretation: no abnormality
Calcium - 2.29
GFR 100, normal creatinine
IgA 1.14 (0.75-4.55)
IgG 8.12 (6.8-18.00)
IgM 0.88 (0.5-3.0)
My RBC's are slightly high, WBC normal, MCV and MCHC low (has been this way for 10+ years), RDW high, all other parameters normal.
I have not had IFE because my hematologist says that if the SPEP is normal, there is no need to order IFE. Is this correct?
She also said that my initial abnormal FLC ratio could be due to inflammation, but I have read that if that were the case, both FLCs would be increased and the ratio would still be normal.
I should mention these tests were all ordered because I have been dealing with paresthesia and neuropathy for a little over a year and a half, and all other tests that I have done (autoimmune panels, MRIs, blood work etc.) have been normal.
I just went for more blood work testing today to see where my levels are now at. Just wanted to know if anyone has any insight into whether further testing should be done.
Thank you!
I also have similar lab results, and looking for any input anyone can give.
July 5, 2016
Free kappa light chains - 16.7 mg/L (3.3-19.4)
free lambda light chains - 3.7 mg/L (5.7-26.3)
Free kappa/lambda ratio - 4.51 (0.26-1.650)
Total protein- 67 (63-82)
Albumin - 39 (33-48)
Electrophoresis interpretation: Pattern unremarkable
Calcium- 2.12 (2.05-2.55)
GFR- 106, normal creatinine
However, I recently had the blood work repeated and my light chain numbers are now normal:
Oct 21, 2016
Free kappa light chains - 15.8
Free lambda light chains - 9.7
Free kappa/lambda ratio - 1.63
Total protein - 71
Albumin - 36
Electrophoresis interpretation: no abnormality
Calcium - 2.29
GFR 100, normal creatinine
IgA 1.14 (0.75-4.55)
IgG 8.12 (6.8-18.00)
IgM 0.88 (0.5-3.0)
My RBC's are slightly high, WBC normal, MCV and MCHC low (has been this way for 10+ years), RDW high, all other parameters normal.
I have not had IFE because my hematologist says that if the SPEP is normal, there is no need to order IFE. Is this correct?
She also said that my initial abnormal FLC ratio could be due to inflammation, but I have read that if that were the case, both FLCs would be increased and the ratio would still be normal.
I should mention these tests were all ordered because I have been dealing with paresthesia and neuropathy for a little over a year and a half, and all other tests that I have done (autoimmune panels, MRIs, blood work etc.) have been normal.
I just went for more blood work testing today to see where my levels are now at. Just wanted to know if anyone has any insight into whether further testing should be done.
Thank you!
Re: Light chain MGUS - criteria for diagnosis
I should also mention that I had a 24-hour urine done, and it said
"Test not performed – unable to calculate. Urine protein concentration is below measurable range"
for protein total.
Urine protein electrophoresis said that "only a faint band of albumin present".
"Test not performed – unable to calculate. Urine protein concentration is below measurable range"
for protein total.
Urine protein electrophoresis said that "only a faint band of albumin present".
Re: Light chain MGUS - criteria for diagnosis
Janoun1975,
I think our situations are quite similar: initially elevated kappa-lambda ratio, owing to a normal kappa and low lambda. Also, like you, as time has gone on, my lambda has begun to rise into the normal range, and my ratio as of a few days ago is down from 2.75 in July to 1.88 now, which is still abnormal, but much closer to the normal range. My hope is that my ratio will normalize by the time of my follow-up appointment 6 months from now, which would pretty much be the final step in ruling out a plasma cell dyscrasia in my case. Fingers crossed.
To address the issues you raised in your post, my understanding of the inflammation-related light chain abnormalities is much the same as yours: that in general inflammation may increase light chains, but usually both at the same time, in a polyclonal way. That said, I recently read a quite new research article that indicated that inflammatory conditions can under some circumstances lead to an abnormality of the ratio, rather than simply an elevation of both light chains above their respective reference ranges.
I will say, however, that it seems odd to think that your initial light chain ratio abnormality would be attributed to inflammation, since your kappa was within the reference range and the factor contributing to the ratio abnormality was the low lambda. So basically if inflammation was the cause we would have to assume that inflammation can selectively suppress, rather than raise, one of the light chains. I'm not a doctor and certainly no expert on these things, but I've never heard of that happening.
Given that your second round of tests revealed a very similar kappa, but a return to the normal range for your lambda and thus your ratio, it seems like this might be very good news for you. Your doctor is most likely correct that a lack of M-protein on an SPEP and a normal free light chain ratio points strongly away from a monoclonal protein disorder, but if you're like me you would probably prefer to get confirmation via serum immunofixation electrophoresis (IFE). The combination of a negative SPEP, IFE, and serum free light chain assessment would go a very long way towards ruling out any plasma cell dyscrasia. If your doctor isn't willing to order an IFE, please be aware that for a relatively modest cost (probably in the range of $150 to $200) you can actually order serum and urine immunofixations yourself from a variety of online labwork companies, although if you want to take this path you will want to google around a bit, as the prices vary considerably from company to company.
Best of luck!
I think our situations are quite similar: initially elevated kappa-lambda ratio, owing to a normal kappa and low lambda. Also, like you, as time has gone on, my lambda has begun to rise into the normal range, and my ratio as of a few days ago is down from 2.75 in July to 1.88 now, which is still abnormal, but much closer to the normal range. My hope is that my ratio will normalize by the time of my follow-up appointment 6 months from now, which would pretty much be the final step in ruling out a plasma cell dyscrasia in my case. Fingers crossed.
To address the issues you raised in your post, my understanding of the inflammation-related light chain abnormalities is much the same as yours: that in general inflammation may increase light chains, but usually both at the same time, in a polyclonal way. That said, I recently read a quite new research article that indicated that inflammatory conditions can under some circumstances lead to an abnormality of the ratio, rather than simply an elevation of both light chains above their respective reference ranges.
I will say, however, that it seems odd to think that your initial light chain ratio abnormality would be attributed to inflammation, since your kappa was within the reference range and the factor contributing to the ratio abnormality was the low lambda. So basically if inflammation was the cause we would have to assume that inflammation can selectively suppress, rather than raise, one of the light chains. I'm not a doctor and certainly no expert on these things, but I've never heard of that happening.
Given that your second round of tests revealed a very similar kappa, but a return to the normal range for your lambda and thus your ratio, it seems like this might be very good news for you. Your doctor is most likely correct that a lack of M-protein on an SPEP and a normal free light chain ratio points strongly away from a monoclonal protein disorder, but if you're like me you would probably prefer to get confirmation via serum immunofixation electrophoresis (IFE). The combination of a negative SPEP, IFE, and serum free light chain assessment would go a very long way towards ruling out any plasma cell dyscrasia. If your doctor isn't willing to order an IFE, please be aware that for a relatively modest cost (probably in the range of $150 to $200) you can actually order serum and urine immunofixations yourself from a variety of online labwork companies, although if you want to take this path you will want to google around a bit, as the prices vary considerably from company to company.
Best of luck!
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