Low overall IgG serum and Low subclasses 1 and 2?

[marcd43]

Hi,

Has anybody ever regularly tested low in overall IgG and subclasses 1 and 2? I don't know what this means or what I should expect next. These results have been confirmed three different times now, so I'm not sure if it is clinically significant or not. I'm being referred to an immunologist and I'm just wondering what to expect. I was also wondering if there is anyone who is in the same boat, and what symptoms do you experience?

Thanks for any help!

Mariann

 

[halcyon]

Do you know what your overall IgG level is? There seems to be a lot of folks here with low subclass 1 and 3 so hopefully they can chime in.

 

[deleder2k]

Maybe you'll get treated with gamma globulins. That does ease ME symptoms for some.

 

[Daffodil]

marc....that means you qualify for an immunodeficiency diagnosis and would be eligible for intravenous immunoglobulin. this could really help you.

whether chronic infections or autoimmune disease cause low IgG, or whether low IgG causes chronic infections or autoimmunity...I have no idea. maybe someone else could chime in.

 

[Jonathan Edwards]

We need to know how low they are. A total IgG of 5 or 6 is not a problem. Autoimmune diseases such as lupus can produce very low IgG at times but most autoimmune disease is associated with high IgG if anything. Chronic infection becomes a problem for some people when IgG gets down to about 3, but it depends on the 'quality' of the IgG and needs to be monitored by an immunodeficiency expert at that sort of level.

 

[marcd43]

My latest overall serum level was 589 mg/dl, my Igg subclass 1 level was 351 mg/dl, and my subclass 2 was 138 mg/dl.
My Igg subclass 3 and 4 were in normal range at 42 and 5.4 respectively.

Not terribly low, but still a bit concerning. I also have Hashimoto's (thyroid removed) and PCOS. In the last 20 years I've had 11 miscarriages (no doctor could ever come up with a reason why, and I've had every test and treatment done under the sun. Babies' genetics all normal). Pregnancies would progress until about the 10th to 12th week before ending. One made it to the 14th but that was the longest. I used to get strep throat about 6-7 times a year and bronchitis every time I caught a cold, but after I had my tonsils removed I get those illnesses less. Now I mostly get weird skin bumps on my scalp, face, and upper body, as well as a rash on my face and upper body every time I get a virus.I go through strange phases where I'm extremely tired, weak, and dizzy, and get a bad headache and muscle/joint pain that moves down into the area just below my rib cage. This is followed by the rash. The last episode included weird cysts that formed just below each of my eyebrows that were very painful.

Unfortunately, I am around a multitude of kids every day because I'm an elementary teacher, which means I'm around a lot of germs.

I sometimes feel like I'm part alien or something!

Any information, advice, or sharing of any similar experiences would be greatly appreciated!

 

[Jonathan Edwards]

589 is not of itself a problem with immunity but the IgG 1 level is quite low. The decision on whether or not it is sensible to use IVIG replacement would depend on evidence of infection and can only really be made by an immunodeficiency expert. Even though I worked in immunology this particular problem was always handled by the specialist immunodeficiency service for me.

It is likely that at least some low IgG situations, which often fall under what is called common variable immunodeficiency, are due to an autoimmune process - perhaps because certain autoantibodies switch off other antibody production. However, nobody has actually found an autoantibody that would do this. I presume that you were tested for antiphospholipid antibodies for the miscarriages. The thyroid is not usually removed for Hashimoto's, but rather for Graves' disease but Graves can convert to Hashimoto's. It sounds as if there is at least one autoimmune problem and maybe this is linked to the low IgG. Whether ME type symptoms can have an autoimmune basis remains unknown, although the evidence with rituximab is suggestive.

IVIG is given for two quite different reasons. It can be given just to provide more immunity if IgG is low. The only real justification for that is if infections are occurring. The other reason is that there is reasonably good evidence that giving other people's IgG to people with autoimmune disease somehow counteracts the bad effects of their autoantibodies. It is very difficult to know why this should happen - it does not make much sense - but it probably does happen. In this situation it does not matter what IgG level you start off with because the treatment is not designed to replace IgG but to counteract the IgG you already have. There are a few trials suggesting this can work in ME. The question would be which if either of these would make sense for you. All immunodeficiency specialists will understand the first reason but not so many the second. If it was a case of having IVIG for the second reason the slightly low level would not be relevant and the reasoning would be the same as for anyone with ME. At present I do not think there are many ME specialists using IVIG, but there may be some. I am unclear whether it is a sensible idea because the evidence so far is limited.

 

[Helen]

[QUOTE="@marcd43, post: 524739, member: 17315"
Not terribly low, but still a bit concerning. I also have Hashimoto's (thyroid removed) and PCOS.
[/QUOTE]

Do you think that you get an optimal treatment to substitute the removal of your thyroid? If you have symptoms of lack of thyroid hormone it could be well worth looking into this too. Hypothyroidism, and particularly lack of the hormone T3, is known to be related to miscarriages.

 

[ukxmrv]

Injections of IG's (IMIG) have along history as a treatment for ME in the UK. Dr Richardson used them. Dr Spur who has just retired also used them and his patients are now fighting to get these injections continued elsewhere.

"2. Immunoglobulin i.m. injections to modulate the immune system in favour of the patient. The
John Richardson Research Group has used this treatment for the past 30years with energy
levels increasing over time from 20% up to 80%. Also heart and autoimmune sequellae have
been minimized. Unfortunately, the proponents of the misnomer CFS have prevented genuine
research into this treatment of ME for at least 30years.

http://www.meresearch.org.uk/wp-content/uploads/2012/12/EvME.pdf

 

[marcd43]

Wow! Thank you all so much for your replies! I really appreciate all of the time and information you put into helping me!

At the time of the miscarriages, my thyroid was checked but only the TSH. Turns out my T3 and T4 were low and my thyroid had grown to the size of a lemon and was pushing my trachea off to the side causing breathing problems. I was on Armour thyroid but it stopped working for me so I am now on NatureThroid and doing better.

I've recently been tested for Lupus and Sjogrens, but came back negative.

I'm waiting for a referral to the immunologist. I do have one daughter (who is my miracle!) that is now 22 years old, and everything seems to have started after she was born. Very difficult time with her pregnancy and then became sick for a year starting the day after she was born. Dropped down to 89 lbs but my doctor couldn't figure out why.

While waiting to see the immunologist, the rheumatologist has additional blood work for me to do:
complement, Total (ch50 units)
complement comp c3 and c4
c1q complement component
c1 inhibitor, protein
c1 inhibitor, functional
retest immunoglobulins

Not sure what these are testing for, but will post when results come back. Again thank you all SO much for your responses on here!

 

[Ema]

I'm waiting for a referral to the immunologist.

Make sure you see a clinical immunologist and not an allergist/immunologist if you are in the US. Most typical allergists are woefully undereducated in this area and often miss the proper diagnosis.

The IDF website can help you find a knowledgeable doctor as well.

http://primaryimmune.org

My doctor says anything under 600 for total IgG levels usually represents a complete failure of the immune system. But to diagnose CVID (common variable immune deficiency), one needs to have a vaccine challenge to see how your body responds. This is all detailed as well on the excellent IDF website.

I'm on subQ IgG replacement and it has definitely played a part in my treatment.

Good luck!

 

[Jonathan Edwards]

my thyroid had grown to the size of a lemon and was pushing my trachea off to the side causing breathing problems.

That figures now.

While waiting to see the immunologist, the rheumatologist has additional blood work for me to do:
complement, Total (ch50 units)
complement comp c3 and c4
c1q complement component
c1 inhibitor, protein
c1 inhibitor, functional
retest immunoglobulins

Not sure what these are testing for, but will post when results come back. Again thank you all SO much for your responses on here!

I think the complement tests are just to dot the i's because the sort of hypocomplementaemic states you get in lupus can rarely occur without ANA ('seronegative lupus'). I doubt it will show anything up but worth doing. Antiphospholipid is the obvious one in the context of miscarriage but obstetricians should have been doing this routinely for repeat miscarriage for the last twenty years or so and I guess you will have had it checked.

 

[melamine]

Make sure you see a clinical immunologist and not an allergist/immunologist if you are in the US. Most typical allergists are woefully undereducated in this area and often miss the proper diagnosis.

The IDF website can help you find a knowledgeable doctor as well.

http://primaryimmune.org

@ marcd43 - I would add that IVIG treatments are very expensive and whether you are determined to be qualified may depend in part on the quality of your insurance and how far an immunologist is willing to set the diagnostic marker in the absence of demonstrable, life-threatening infections, or chronic, diagnostically simple infections, which are not always the kind we here are dealing with. My personal experience with immunologists at teaching hospitals who are not interested or educated in less classic forms of immune deficiency is that you should not waste your time. The link provided by Ema is your best resource if you want to explore this route.

My IgG 1 has been deficient for at least 5 years, causing low but not sub-normal overall IgGs. IgG 3 was borderline low a few years ago. None are very high. Consistently low C3. C4 was a little low at one time but not now. Labs indicate hyper IgM for at least 7 years. ANA positive for several years and although I have too many symptoms to remember at any one time, including sicca syndrome (not classically defined Sjogren's), my symptom profile is different than lupus and many of them had definable infectious or suspected toxic and/or allergic origins. My most threatening symptoms involve a progressing neuropathy that has never been properly diagnosed and may hinge on the IgM as much as anything. I have high titers of EBV, adenovirus, and all coxacki Bs. I cannot remember the last cold or flu I've gotten but have had symptoms of a chronic upper respiratory infection since a chronic- acute one 8 years ago that also caused symptoms of heart failure - all largely misdiagnosed. My only vaccine challenge was about a year and a half after that and was normal "enough". At any rate, the university immunologist who did it was not interested in my history or symptoms or other labs, so there was no question of failure to interpret. It is best to avoid as many inadequate doctors as possible so as to avoid disappointment and to not contaminate your record with misdiagnoses. When you consult the most reliable specialists in the area where you are seeking an opinion, you can feel more confident that it is the last word on the subject.

 

[anniekim]

Injections of IG's (IMIG) have along history as a treatment for ME in the UK. Dr Richardson used them. Dr Spur who has just retired also used them and his patients are now fighting to get these injections continued elsewhere.

"2. Immunoglobulin i.m. injections to modulate the immune system in favour of the patient. The
John Richardson Research Group has used this treatment for the past 30years with energy
levels increasing over time from 20% up to 80%. Also heart and autoimmune sequellae have
been minimized. Unfortunately, the proponents of the misnomer CFS have prevented genuine
research into this treatment of ME for at least 30years.

http://www.meresearch.org.uk/wp-content/uploads/2012/12/EvME.pdf

@ukxmrv do y know when Dr Richardson was was alive and until Dr spurr retired whether they gave IM Ig injection based on the first reason Jonathan Edwards gave in this thread or the second? Ie, did they only give IG to ME patients with low IgG or to ME patients with normal IgG in the hope of modulating the immune system?

I ask because when I looked online about immunoglobulin treatment by dr richardson found this, 'Replacement therapy with IgG is given to restore normal homoral immune function. Some clinicians use the I.V. infusions but we for so many years have used I.M. injections. Professor R. Loria in personal communications has demonstrated the vortex of effects which occur when IgG is given I.M. rather than I.V. and thus it has more effective results. Also, instead of large amounts of extended intervals, we find that on average about 500mg weekly has a ‘smoother’ and more beneficial effect. However, before this therapy is given it is wide to do the serotological tests alluded to earlier and show these to be positive.' The serological tests mentioned earlier are IgG testing and viral panel. Many thanks

 

[ukxmrv]

Sorry @anniekim I never asked Dr Richardson or S why they used IMIG instead of IVIG? Had always assumed that it was due to the problems of infusing

Thanks for posting that info!

p.s has anyone else had problems getting IG testing through the NHS?

 

[Stacey1121]

We need to know how low they are. A total IgG of 5 or 6 is not a problem. Autoimmune diseases such as lupus can produce very low IgG at times but most autoimmune disease is associated with high IgG if anything. Chronic infection becomes a problem for some people when IgG gets down to about 3, but it depends on the 'quality' of the IgG and needs to be monitored by an immunodeficiency expert at that sort of level.

@Jonathan Edwards I know this is an old post but if you would be so kind I have a question. My lab results are as follows:

Immunoglobulin G, Qn, Serum 490 Low mg/dL 700 - 1600 02
IgG, Subclass 1 284 Low mg/dL 422 - 1292 03
IgG, Subclass 2 110 Low mg/dL 117 - 747 03
IgG, Subclass 3 24 Low mg/dL 41 - 129 03
IgG, Subclass 4 5 mg/dL 1 - 291 03

I have a positive pcr test from dna connecxions for borellia burdorferi, borellia recurrentis, babesia divergens, ehrlichia chaffensis, and positive titers for EBV, HHV-6, C. PNEUMONIAE, Mycoplasma, C.ALBICANS and CMV. I was at Envita Medical center in AZ for months of IV antibiotics, ozone and other nutritional IV for the lyme, infections along with mycotoxins from mold toxicity. I had asked the docs at Envita about these immune results and they said they were low due to the infections and that if I got rid of the infections, my immune system would work better. I even asked about IVIG when I was there but they said it they had really not found it helpful?

I have been home for 4 months, am still not well, and searching for answers. Recently I have come across information that seems to suggest I might have a primary immune problem based on my labs? I was referred by a physician friend to Dr. Isaac Melamed, MD http://immunoehealth.com/ and have an apt with him in CO a few weeks and am wondering if its possible to know if I have had a primary immune deficiency that lead to all of this infection? I have taken good care of myself for many years with quality food, supplements, and exercise - none of this has made sense to me. I did look at my 23&Me results with regard to immunity and I do have mutations - I am not sure which might be playing a part in this.

I came across this list of tests re immune system on another forum and I would like to go to CO with the best info I can for the immunologist - and am wondering if any of these tests might be helpful. My doc here in CA could order them:

This is a list of the important tests to confirm an immune deficiency:

Serum Complement
Lymphocyte Proliferation with Antigens and Mitogens
Humoral Immunity Panel
Lymphocyte Subset Panel (Total Lymphocyte Enumeration)
B Cell Memory and Naive Panel
Cytokine Panel (ARUP Cytokine 12)

I did have these tests done in the fall and I think this is the cytokine panel they are referring to and it was all normal:

Interleukin 2 <5 pg/mL <=12 01
Interleukin 2 Rec (CD25), Solu
312 pg/mL <=1033 01
Interleukin 12 <5 pg/mL <=6 01
Interferon gamma <5 pg/mL <=5 01
Interleukin 4 <5 pg/mL <=5 01
Interleukin 5 <5 pg/mL <=5 01
Interleukin 10 <5 pg/mL <=18 01
Interleukin 13 <5 pg/mL <=5 01
Interleukin 1 beta <5 pg/mL <=36 01
Interleukin 6 <5 pg/mL <=5 01
Interleukin 8 <5 pg/mL <=5 01
Tumor Necrosis Factor - alpha
18 pg/mL <=22 01
Interleukin 17 <5 pg/mL <=13 01

Thank you kindly in advance for any of your thoughts....

 

[Jonathan Edwards]

To be honest I would not take any particular notice of any of these tests without first establishing clear clinical evidence of a specific infection at a specific site. You do not mention any specific symptoms that would point in the direction of infection. Infections do not cause low immunoglobulins as a rule. If anything it is the other way around, but most people with lowish immunoglobulins are fine.

Tests for infections need to be considered in the light of good clinical evidence. Otherwise they are very likely to be red herrings.

 

[Stacey1121]

Thank you so very kindly for your response. I did forget to list symptoms - well lets start with the obvious then memory problems, brain fog, extreme fatigue, muscle weakness, low blood pressure, elevated pulse, Raynaud's disease (hands and feet turn bright red with blood pooling and then white and numb at times), hot\cold intolerance, SIBO & candida with significant impaired digestion, ibs, intense body pain, total numbness and loss of muscle control in right arm at times, hard to control hypothyroid (I have to take small pieces of thyroid all day bc if I take the full dose it at once it puts me to sleep and I am now up to 250 mcg of synthoid with 50 mcg cytomel), extremely low cortisol and have to supplement, my hormones production is impaired and I have to replace with estrogen, testosterone, dhea, pregnenolone, impaired vision that keeps changing, chronic sinus issues, recurrit bronchitis, and I am depressed (who wouldnt be). When I left for AZ I was pretty non functional - when I got home from treatment in November (continuing abx treatments thru port, ozone, supplements and hormones) I got a bit stronger and then I got a really bad bout of sinus\bronchitis and have not been the same since. I vacillate between bad days and the occasional mediocre day. A few weeks ago I had TVAM surgery (like CCVSI) for the dysautonomia and it did not help at all. The idea of working with an immunologist is the only thing I can think of at this point....

 

[Jonathan Edwards]

I am not in a position to give medical advice but those do not sound like the symptoms of any particular infection to me (with the exception of bronchitis), and I doubt I would ask for immunological tests to investigate. They do not sound like the symptoms an immunodeficiency.

 

[Stacey1121]

Now I am really confused - So my symptoms correlate with my infections - and if I am having a hard if not impossible time getting rid of (or staying better from) my infections - couldn't that be at least partially bc of low immunoglobulins. Isn't low immunoglobulin indicated as a problem with infectious disease? It seems I have an impaired immune system based on my immunoglobulin results don't i? Wouldn't an immunologist be able to help me with ivig to help bring up my immunoglobulin levels so I can better fight the infections I have and not get sicker?