I've been (officially) smoldering (IgG kappa) since October 2017 and testing frequently with relatively stable numbers. I've always assumed IgG and gamma globulin are the same thing and just reported twice in lab results in slightly different formats.
However, is this really true. Are IgG and gamma globulin the same thing?
Until now, my IgG has ranged from 1780-1860. The gamma globulin report was similarly stable, from 1.65-1.94. Both are abnormally high, of course. My M-spike ranges from 1.4 to 1.7.
My last two lab reports, though, reported an abnormally low gamma globulin. The first time this happened, I figured it was just an error in how they entered the data into my portal for viewing. The second time, I contacted the lab and they seem to think it's correct. These are my last 4 results:
IgG Gamma Globulin M-Spike
1810 1.70 1.40
1800 1.75 1.45
1780 0.21 1.59
1840 0.25 1.70
I'm wondering if the gamma globulin results are actually correct. I still don't think so. I haven't spoken with my specialist about it since the M-spike and kappa/lambda ratio that we monitor most closely are stable. He always contacts me if anything surprising pops up.
Thanks for any wisdom.
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Defcon Dragon - Name: Defcon Dragon
- Who do you know with myeloma?: myself, smoldering
- When were you/they diagnosed?: October 2017
- Age at diagnosis: 55
Re: Are IgG and gamma globulin the same thing?
I am not sure what the Gamma Globulin test was showing.
Typically in my tests I get a Serum Protein Electrophoresis (SPEP) which measures the M spike and in my case is IgG in the Kappa region. I note you have M spike that appears to be climbing as you noted from 1.4 to 1.7 over the 4 tests. There appears to be roughly related to the Gamma Globulin falling but I don't get this separate test so not sure what it is indicating. You will have to ask your oncologist as to the what that separate measurement means. I get a Serum Free Light Chain Assay which tracks my Myeloma and for me is a lot more sensitive as my M spike is only .2 and has remained stable. The Free Light Chain for me is much more sensitive..
A separate test measuring the Immunoglobulin's is done to determine if there is an immune system deficiency.. Below is a typical normal range but it will vary by lab.
Normal Values
Serum globulin: 2.0 to 3.5 g/dL
IgM component: 75 to 300 mg/dL
IgG component: 650 to 1850 mg/dL
IgA component: 90 to 350 mg/dL
The examples above are common measurements for results of these tests. Normal value ranges may vary slightly among different laboratories. Some labs use different measurements or test different samples. .
Based on these and what you posted it would appear that your IgG immunoglobulin is in the high end of normal and has been relatively stable.
Typically in my tests I get a Serum Protein Electrophoresis (SPEP) which measures the M spike and in my case is IgG in the Kappa region. I note you have M spike that appears to be climbing as you noted from 1.4 to 1.7 over the 4 tests. There appears to be roughly related to the Gamma Globulin falling but I don't get this separate test so not sure what it is indicating. You will have to ask your oncologist as to the what that separate measurement means. I get a Serum Free Light Chain Assay which tracks my Myeloma and for me is a lot more sensitive as my M spike is only .2 and has remained stable. The Free Light Chain for me is much more sensitive..
A separate test measuring the Immunoglobulin's is done to determine if there is an immune system deficiency.. Below is a typical normal range but it will vary by lab.
Normal Values
Serum globulin: 2.0 to 3.5 g/dL
IgM component: 75 to 300 mg/dL
IgG component: 650 to 1850 mg/dL
IgA component: 90 to 350 mg/dL
The examples above are common measurements for results of these tests. Normal value ranges may vary slightly among different laboratories. Some labs use different measurements or test different samples. .
Based on these and what you posted it would appear that your IgG immunoglobulin is in the high end of normal and has been relatively stable.
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Ron Harvot - Name: Ron Harvot
- Who do you know with myeloma?: Myself
- When were you/they diagnosed?: Feb 2009
- Age at diagnosis: 56
Re: Are IgG and gamma globulin the same thing?
As far as I know, gamma globulins and IgG are different, although IgG is one of the proteins that makes up the gamma globulin family of proteins.
It's helpful if you look at an SPEP graph to understand this discussion:
https://en.wikipedia.org/wiki/Myeloma_protein
Gamma globulins are made up primarily of lgG, IgA and IgM immunoglobulins. IgG, IgA and IgM immunoglobulins can also be present in the beta region. Therefore, a gamma globulin reading is not a surrogate for an IgG reading since it also contains other immunoglobulins and not necessarily all of the immunoglobulins in your system.
My SPEP results breaks up the protein readings into albumin, alpha 1 & 2 globulins, beta 1 & 2 globulins, the abnormal protein band (m-spike) and gamma globulin. Your involved immunoglobulin (in my case, also IgG) will typically migrate and appear as a narrow spike in the gamma region on the SPEP graph, but it can also show up in the beta-2 region and sometimes in the alpha region. My M-spike happens to reside in the beta-2 region, so my beta-2 is always high on my SPEP test results.
Interestingly, while I have an IgG M-spike and my calculated polylconal IgG level is within the normal range (along with my IgA and IgM levels also being normal), my gamma globulin level always reads low on my SPEP. Go figure.
It's helpful if you look at an SPEP graph to understand this discussion:
https://en.wikipedia.org/wiki/Myeloma_protein
Gamma globulins are made up primarily of lgG, IgA and IgM immunoglobulins. IgG, IgA and IgM immunoglobulins can also be present in the beta region. Therefore, a gamma globulin reading is not a surrogate for an IgG reading since it also contains other immunoglobulins and not necessarily all of the immunoglobulins in your system.
My SPEP results breaks up the protein readings into albumin, alpha 1 & 2 globulins, beta 1 & 2 globulins, the abnormal protein band (m-spike) and gamma globulin. Your involved immunoglobulin (in my case, also IgG) will typically migrate and appear as a narrow spike in the gamma region on the SPEP graph, but it can also show up in the beta-2 region and sometimes in the alpha region. My M-spike happens to reside in the beta-2 region, so my beta-2 is always high on my SPEP test results.
Interestingly, while I have an IgG M-spike and my calculated polylconal IgG level is within the normal range (along with my IgA and IgM levels also being normal), my gamma globulin level always reads low on my SPEP. Go figure.
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Multibilly - Name: Multibilly
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: Smoldering, Nov, 2012
Re: Are IgG and gamma globulin the same thing?
Thank you so much for your replies. Based on what you've told me, it looks like my gamma globulin and beta globulins have flip-flopped and my IgG is now showing up in the beta region. Previously, gammas were always high, betas normal or low in the SPEP. Now gamma is low, beta is high.
Beta changed from 0.57 (low) in March to 2.32 (high) in my June tests. I don't get a Beta 1 and Beta 2 report. It just says "Beta" even though I get Alpha 1 and Alpha 2.
The IgG comes from a separate test and, except for the very first one, it never reports IgA or IgM. Those were both a little low on the first one, but I guess we're only really concerned with the IgG. Now I'm really curious to see what the doctors have to say about this flip-flop!
Thanks again for your input. It really helps.
Beta changed from 0.57 (low) in March to 2.32 (high) in my June tests. I don't get a Beta 1 and Beta 2 report. It just says "Beta" even though I get Alpha 1 and Alpha 2.
The IgG comes from a separate test and, except for the very first one, it never reports IgA or IgM. Those were both a little low on the first one, but I guess we're only really concerned with the IgG. Now I'm really curious to see what the doctors have to say about this flip-flop!
Thanks again for your input. It really helps.
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Defcon Dragon - Name: Defcon Dragon
- Who do you know with myeloma?: myself, smoldering
- When were you/they diagnosed?: October 2017
- Age at diagnosis: 55
Re: Are IgG and gamma globulin the same thing?
Even if you have an IgG isotype, it's good to also monitor your IgA and IgM levels. This is because you want to be on the lookout for your IgA and / or IgM levels becoming suppressed (a condition known as immunoparesis). Immunoparesis in a smoldering patient is a potential indicator that one may be at higher risk of developing symptomatic myeloma.
You might want to browse the article I reference below.
The cost difference between testing just your total IgG level versus testing all three immunoglobulin levels is quite small, so I'm not sure why your doctor isn't ordering all three (there is a single lab test code for ordering all three).
Article reference:
Sørrig R, et al, "Immunoparesis in newly diagnosed Multiple Myeloma patients: Effects on overall survival and progression free survival in the Danish population," PLoS ONE, Dec 7 2017 (full text of article)
Abstract:
Immunoparesis (hypogammaglobulinemia) is associated to an unfavorable prognosis in newly diagnosed multiple myeloma patients. However, this finding has not been validated in an unselected population-based cohort. We analyzed 2558 newly diagnosed multiple myeloma patients in the Danish Multiple Myeloma Registry representing the entire multiple myeloma population in Denmark from 2005–2013. Two-thousand two hundred and fifty three patients (90%) presented with reduction below lower normal levels of at least one uninvolved immunoglobulin. Using multivariable Cox regression we found that high age, high ISS score, high LDH and IgA multiple myeloma were associated to both shorter overall survival and progression free survival. Furthermore, bone marrow plasma cell % was associated to short progression free survival. Immunoparesis had no independent significant effect on OS (HR 0.9 (95%CI: 0.7;1.0; p = 0.12)). Likewise, the number of suppressed immunoglobulins or the relative degree of suppressed uninvolved immunoglobulins from lower normal level (quantitative immunoparesis) was not associated to OS in the multivariable analysis. However, quantitative immunoparesis with at least 25% reduction (from lower normal level) of uninvolved immunoglobulins was associated to shorter PFS for the entire population. The impact of quantitative immunoparesis on PFS was present irrespective of calendar periods 2005–2008 and 2009–2013. Our population-based study does not confirm that immunoparesis at diagnosis is an independent prognostic factor regarding OS. However, quantitative immunoparesis is associated to a shorter PFS.
You might want to browse the article I reference below.
The cost difference between testing just your total IgG level versus testing all three immunoglobulin levels is quite small, so I'm not sure why your doctor isn't ordering all three (there is a single lab test code for ordering all three).
Article reference:
Sørrig R, et al, "Immunoparesis in newly diagnosed Multiple Myeloma patients: Effects on overall survival and progression free survival in the Danish population," PLoS ONE, Dec 7 2017 (full text of article)
Abstract:
Immunoparesis (hypogammaglobulinemia) is associated to an unfavorable prognosis in newly diagnosed multiple myeloma patients. However, this finding has not been validated in an unselected population-based cohort. We analyzed 2558 newly diagnosed multiple myeloma patients in the Danish Multiple Myeloma Registry representing the entire multiple myeloma population in Denmark from 2005–2013. Two-thousand two hundred and fifty three patients (90%) presented with reduction below lower normal levels of at least one uninvolved immunoglobulin. Using multivariable Cox regression we found that high age, high ISS score, high LDH and IgA multiple myeloma were associated to both shorter overall survival and progression free survival. Furthermore, bone marrow plasma cell % was associated to short progression free survival. Immunoparesis had no independent significant effect on OS (HR 0.9 (95%CI: 0.7;1.0; p = 0.12)). Likewise, the number of suppressed immunoglobulins or the relative degree of suppressed uninvolved immunoglobulins from lower normal level (quantitative immunoparesis) was not associated to OS in the multivariable analysis. However, quantitative immunoparesis with at least 25% reduction (from lower normal level) of uninvolved immunoglobulins was associated to shorter PFS for the entire population. The impact of quantitative immunoparesis on PFS was present irrespective of calendar periods 2005–2008 and 2009–2013. Our population-based study does not confirm that immunoparesis at diagnosis is an independent prognostic factor regarding OS. However, quantitative immunoparesis is associated to a shorter PFS.
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Multibilly - Name: Multibilly
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: Smoldering, Nov, 2012
Re: Are IgG and gamma globulin the same thing?
Yep, sounds like it's time to look at my non-involved immunoglobulins again. The thing that caught my attention is the mirror image of my last two gamma globulin vs. beta globulin results (graphs attached).
Now that I know I can be high in IgG but low in the total "Gamma Globulins" it makes a bit more sense.
I see my myeloma specialist every 6 months but he tends to call me if something looks off. I'm halfway expecting a phone call on this one.
Now that I know I can be high in IgG but low in the total "Gamma Globulins" it makes a bit more sense.
I see my myeloma specialist every 6 months but he tends to call me if something looks off. I'm halfway expecting a phone call on this one.
- betagammaflip.png (52.25 KiB) Viewed 4365 times
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Defcon Dragon - Name: Defcon Dragon
- Who do you know with myeloma?: myself, smoldering
- When were you/they diagnosed?: October 2017
- Age at diagnosis: 55
Re: Are IgG and gamma globulin the same thing?
I can't speak for you doctor, but he is likely just concentrating on looking at your m-spike, free light chain values and your CRAB-related blood markers (calcium, creatinine, hemoglobin) to see if you might be clinically progressing or developing any end-organ damage.
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Multibilly - Name: Multibilly
- Who do you know with myeloma?: Me
- When were you/they diagnosed?: Smoldering, Nov, 2012
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