Hey, all, just wondering. My oncologist has never had my IgG checked. Yet it was a low IgG that led my PG to send me to a specialist who then diagnosed the CLL in the first place (but IgG had come back up at that time for some reason). I just requested the IgG test and I am the lowest ever 4.7 or so. and it has been on a gentle decline since diagnosis Dec 2019 (when it had popped up a bit for some reason). It was midway when I had infectious disease doc check it in 2022. So question -- Is this a normal sign of CLL progression to have lower and lower IgG? When people talk about us being immunocompromised, are they talking IgG or neutrophils or just the fact that we have an immune disorder (b cells). I've never had an IgG supplement cause, again, it was never tested by oncologist since diagnosis. By the way, I always seem to have a very mild cold, not major cold, but just hey fever type confestion, bit of itchy throat type. I did have a bigger deal with my second Covid experience but no doc or hospital and, all went away. So can't say I've had a serious infection from this.
Lowering IgG as sign of progression? - CLL Support
Lowering IgG as sign of progression?
It's common, but not inevitable to have falling immunoglobulin counts when we have CLL. It's yet another instance of the heterogeneous nature of CLL.
With respect to the many ways that CLL can impact our immune system, I summarised what I'd learned about this topic in this post from 9 years ago :
Explainer: what is the immune system and how does CLL affect it?
healthunlocked.com/cllsuppo...
With respect to qualifying for IgG replacement therapy, you might meet the common USA IgG threshold of under 5.0. That threshold seems to vary by health insurance company and the threshold is generally lower (typically under 4.0) in other countries. Your good news is that you are fortunate in not having had any serious infections that are also a qualifying condition as well as having low IgG.
Some of us can manage very low IgG counts while still managing to avoid serious infections. Remember, your IgG count is the sum of all your different IgG classes (IgG1 to IgG4) for all the different bugs your immune system has recognising immunoglobulins, from both past vaccinations, boosters and infections. How well what you have works depends on how current they are for what you encounter (which is why COVID-19 and flu boosters are important) as well as how well the rest of your immune system works. Immunoglobulins can work in different ways, such as by neutralising viruses, so they can't invade our body cells to replicate, to actually directly destroying the invaders, to marking them for phagocytes to engulf them. Also, other IgG classes function in different ways. Currently, other Ig classes can't be supplemented and IgG doesn't work quite as well as IgA, for example. IgA preferentially concentrates in our respiratory, gut and urogenital systems, so we are more liable to infections there if our IgA is very low.
Neil
Marvelously helpful as usual, Neil. Thank you. As might be expected, my IgA is also out of range. Oddly, they were low before diagnosis but then came up to normal at time of diagnosis--? And now drifted back down even lower. I do think I am going to ask about getting supplementation at my next appt in February. By the way, you mention iron and lactoferrin at the bottom of your article on immunity -- any significance? I know iron is a negative for bacterial infections.
Looks like the comment that resulted in my comment on iron was deleted. There was a bit of frivolity about iron animals in the comments though 
AussieNeil has given a great answer as usual. I'll just share some experience I have had. 2024 was my year of very low IG (g, a and m) all well below minimum all year. So in October my Haemo gave up hoping they would go up and qualified me for IVIg and put me on Line 2 Zanubrutinib at the same time. Lymphocytes were just nudging a very tiny 12 at the time, but IG and platelets were cactus. 2024 has been my year of infections, I'm a young fellow as CLL goes and I have never had this many infections before- colds that morph into pneumonia, every tiny skin lesion infected needing antibiotics, diarrohea that lasts for weeks and will not go away, cellulitis,......the list goes on and on. I think I was lucky to have a fortnight without a problem. Anyway the 2 treatments have everything sorted and 2 months into treatment I am better than I have been all year. Oh and I feel fantastic when I walk out of IVIg, invincible. Maybe that is just what it feels like to be well and normal
Living with CLL I think it's easy to forget what it feels like to be well and normal, which makes it feel so sweet when it does. Glad to read you are feeling fantastic and long may it continue!
Can you tell me what "Line 2 Zanubrutinib" is? Is this your first treatment? Thanks
Line 1 was O+V for 12 months completed Feb 2023. Line 2 is Zanubrutinib started Oct this year. Each treatment is termed a line - like a military trench line as the enemy CLL has "broken through"
Thanks, ArtistBlacksmith
Hi ArtistBlacksmith Great to hear your feeling better with treatment. I am hoping to begin IVIG next week. So tired of being sick this year too. Looking forward to it!
Lorna
I really hope it works for you too! I first had some back in 2022 when platelets crashed (the full platelet dose of 100g in 1L) and was amazed how I instantly felt so much better- notably fatigue vanished. Now it is the much reduced Ig dose 40g in 400ml and it worked wonders too- infections have almost disappeared. I'll probably be weaned off it in a few months to see how the Zanubrutinib is doing, but it has been wonderful yet again. I am so grateful to the almost 100 donors a year it takes to make my dose.
I have had 6 hematologists since my initial diagnosis in 2003. My 6th and present hematologist was the first one who mentioned IgG and had a lab level ordered. I was referred to him because he had specialized in CLL. He determined that I no longer needed to receive IVIG every 4 weeks and put me on an eight week course. I am doing well.
Hello Vlaminck
As AussieNeil says we are all different. I have very aggressive CLL with ALC doubling every 2.5 months, however I have never been tested for IgG. This is due to the fact that I have only had two head colds in almost 8 years since diagnosed with CLL. I do however have more problems with allergic reactions like shingles and poison ivy. I used to be able to pull poison ivy with bare hands, no problems. I also have not had a cold sore since I had singles. Blessings.
I think that ivy allergy develops with age, at least it did for me. I too could pull it up by the roots, and never worried about sitting on it or whatever as a child. No problem. Later on, assuming the same would continue, I pulled up some poison ivy roots -- and WOW. Big case and I was not knowledgeable about how the oil can spread. Pretty miserable time of it. More recently I take homeopathic pills and they seem to work! But then, I don't go pulling up the roots anymore without gloves.
BigDee -
Just to be clear - shingles is not an allergic reaction. It's the reactivation of the herpes zoster virus that had been dormant in nerves ever since you had chickenpox as a child.
=seymour=
Hello SeymourB
I have never had chicken pox. That is why I mentioned the lack of cold sores (Herpes zoster) since I had shingles. I used to get core sores 2-3 times a year, not now.
BigDee -
Were you ever vaccinated with the live chickenpox/zoster vaccine?
=seymour=
Hello SeymourB
Good question, but not that I know of. When I was younger I missed all the childhood diseases instead my brother contracted everything. I did have mumps which destroyed my hearing I was 4 years old. The only shot that I recall having was DPT booster which unfortunately turned out was the only thing I have ever been allergic to. Not sure if chicken pox vaccine even available where I lived.
Great question.
IgG is made by B cells, which are the cells that are cancer cells in CLL.
so overtime as the cancer CLL B cells increase and the normal B cells decrease, less IgG is made. This results in a weaker immune system.
in my case, I had nonstop severe sinus infections prior to the Covid pandemic, for five years before anyone suggested checking checking IgG. it was very low, and I started getting infusions and felt better than I had in years.
As the CLL progress, the frequency of infusions increased to maintain appropriate levels.
After first treatment, I needed the infusions once every three months as opposed to every one month
after I relapsed and especially when I started treatment again, I needed IgG much more frequently.
So bottom line for you is that if your IgG is low and you have a lot of infections, you can qualify for infusions and significantly reduce the number of infections that you have.
Typically, at least in the USA, you cannot get the infusions covered unless you have had a lot of infections, and low IgG.
hope this helps.
Good luck and God bless
Ski pro
Vlaminck -
Low IgG is only one aspect of our immunocompromised state. It's simply the easiest to test.
The more that scientists look into how all the cells in the immune system interact, the more oddities they find due to CLL, and not necessarily due to marrow being overfilled with lymphocytes. That new knowledge has not lead to better testing or therapies yet, though.
Unfortunately, due to the complexity of the immune system, there are no overall tests of immune function. The best is perhaps a vaccine titer test, where the doctor (usually an allergist/immunologist) tests blood for antibodies to a standard vaccine, usually a pneumococcal pneumonia vaccine. Then they vaccinate (even if you've already had the vaccine). wait 6 to 8 weeks, and then check the levels again and compare to the earlier test. Pneumococcal pneumonia is used because it has quite a few serotypes (variants) that gives them more targets to test. There's also several pneumococcal pneumonia vaccines. I'm not sure which one they pick these days. Back when I had it done, they chose either Prevnar13 (PCV13) or Pneumovax23 (PPSV23), which elicit antibodies to 13 or 23 serotypes, respectively. Different brand names are used in different countries. I believe there is now a PCV20.
The titer test exercises almost the whole chain of immunity - from innate immune cells recognizing and bringing antigen to lymph nodes to present to T-cells and B-cells, to B-cell development into plasma cells to produce the serum antibodies. A titer test won't identify where in the chain the failure occured, though. There are probably additional tests that an allergist can do to identify other malfunctions, such as IgA or IgG subclass deficiencies.
Despite marketing and thousands of poorly design studies to the contrary, there really is not much we can do to inexpensively and reliably help our immune system beyond eating a balanced diet, getting good sleep, and avoiding stress. Vitamin D supplementation is recommended for all elderly people, but high doses have not proven useful.
So IVIG or SCIG (SubCutaneousl ImmunoGlobulin) and CLL treatment itself are the 2 ways to address immune system issues when IgG is identified as a weak link in the chain. Treatment itself can suppress immune function. CD20 therapy *rituximab and obinutuzuman) suppresses B-cells long after the last infusion. Usually 6 months is cited, but that's probably the soonest that B-cells might show back up. Several papers have found that some people still do not make sufficient antibodies even several years after last infusion.
Many, if not most specialists do not seem to care enough to even test immunoglobulins or lymphocyte subset counts (counts of T-cells, NK-cells, and B-cells). I suspect that many specialists do not feel qualified to assess immune function - but they should refer to immunologists, I think.
Infection rates only roughly correspond to immunoglobulin levels. People with high levels of immunoglobulins may experience multiple infections per year. People with low immunoglobulins might not. Behavior is a factor, as are inherited genetics. Additional testing can identify inherited immune defects made worse by CLL.
=seymour=
Thank you, Seymour. I very interesting read. I just had another blood test today, because doc was talking treatment before cause of 130 platelets, Will see how these other factors show up now (neutrophils,etc)
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