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Hepatitis Researcher, please give me your opinion regarding Immunoglobu...
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Hepatitis Researcher, please give me your opinion regarding Immunoglobulin M & G deficiency.

Hepatitis Researcher, please give me your opinion regarding Immunoglobulin M & G deficiency.

I’m a 38 years old female, without any identified diseases, except Hepatitis C.  Sort of athletic with normal body weight: now ~ 120 lbs at 5’7”.

Liver fibrosis was stage 2 (per biopsy of 2005), liver fibrosis was stage 1-2 (per Fibro Sure of 2007).
My latest treatment consisted of 98+ weeks of daily high dose Infergen and 1200 mg (and more) daily Riba.  Also, I required Neupogen shots on avg. 2x300 mg per week.  
3.5 months post tx I was sill UND.

My question:  at 3.5 month post tx my IgM concentrations were low – 29 mg/ dL (with reference normal levels: 40-271).  All other Immunoglobulins were in normal range.

Most recent blood test (at 5.5 months post tx) was even lower plus IgG became slightly low:

IgM: 18  L (reference  40-271 mg/dL)
IgG  646  L (reference 694-1618 mg/ dL)
IgA 153       (reference 81-463 mg/dL)
IgE  109       (reference <or = 114)

Total protein was lower than usual, but still in normal low:  

Protein, total 6.3 (reference 6.2-8.3 g/dl) --- usually it is ~7.4
Albumin                 3.9  (reference 3.5-4.7 g/dl)
Alpha-1-globulins  0.2  (reference 0.1-0.3 g/dl)
Alpha-2-globulins  0.7 (reference 0.5 – 1.0)
Beta Globulins        0.8 (reference 0.8 – 1.4)
Gamma Globulins   0.7 (reference 0.6-1.6)
Interpretation:          Normal Pattern

All my Immunoglobulins were in normal (mid) range in 2004.

I guess I’m more concern that during last two months (from 3.5 months post tx to 5.5 months post tx) Immunoglobulins levels becoming lower and lower.

One little detail, I was fasting prior to my first test and I was not fastig  prior to my latest test.

What does it mean?
Does it mean that I need more immunizations to “remind” my body, so to say.

Or is it possible to have anti-IgM & G (if it exist in nature).

I’ll appreciate any impute, opinion, advise.

Thank you and all the best!!
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13 Comments Post a Comment
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Avatar_f_tn
All opinions will be greatly appreciated!! :-)
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Avatar_dr_m_tn
As you can see there is a wide range of "normality"  in these immunoglobulin levels. There is a chance that a portion of your Plasmacells/B lymphocytes went into apoptosis  resulting from the IFN/Riba combo, resulting in an overall low level of Immunoglobulins. How does the diffential white count look - absolute numbers of lymphocytes- and is the white count overall on the low side? To elucidate the percentage of B cells in your total lymphocytes, a flow cytometry analysis could be done to see if there is some selective B-cell percentage/absolute number  deficiency. Probably it is something like a "shocked bone marrow" syndrome, as a result of therapy, of which you will slowly recover. Meanwhile, if you are concerned, a hematologist is the person to assure there is no dangerous cause for the low B-cell activity. I doubt however that he will order any more tests if the differential comes bvack within reasonable limits.
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Avatar_dr_m_tn
yes it is also possible that you have an elevated level of anti IGM, masking your true IGM level, as a mild form of autoimmune disease, but remembering that low to moderate levels of Autoantibodys are normal and needed for normal functioning of our systems. That is why IVIG ( Intravenous Immunoglobulin Therapy) is given for several autoimmune disorders, so that these anti-antibodies can neutralize the dangerous autoantibodies and also various receptors, cytokines etc against which we have a myriad of "physiological "autoantibodies.
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Avatar_f_tn
Thank you very much for your reply!

I don't have right now my CBCs counts, but all my cells counts have been on the lower end (slightly below normal). WBCs in August (3.5 month post tx) were ~3.9k (normal 4.0-10.5), RBCs ~4.0 (normal 3.8--5?).  I'm happy that my Absolute Neutrophils and Lymphs are in low normal range now (2k and 1.4k correspondently).  However, similar CBCs counts persisted throughout last two months without any improvement on RBCs side and with slight fluctuations in WBCs counts (3.9 to 4.3 - to ~3.9 again in October -- at 5.5 months post tx). All relative values (%) or differentiation of blood cells are in normal values.

I'm concerned that while CBCs have not changed in one way or another, my Immunoglobulin became slightly reduced.

Do you think these Immunoglobulin reductions without reductions (or increases) in CBCs counts are pretty much normal in recuperating "shocked bone marrow"?

During my past interferon treatments, my WBCs were in normal mid-rang (5-6k) after 6 months post tx.  Definitely, this time my bone marrow was significantly more suppressed, requiring about 95 weeks of Neupogen injections for its support.

In August (at 3.5 months post tx) I was checked for multiple antibodies and I was in mid-normal range for tested antibodies... but at that point my Immunoglobulins were in normal range except IgM at 29 (low, but not as low as in October at 18 mg/dL).

Do you think new tests for antibodies may bring different results?

Here is one new problem I developed during last two months -- I literally and figuratively have too much gas – yes, I make my contributions to Global Warming. :-)

I asked my Dr. to check for celiac disease, so I had tests for TTG antibody IgA and Gliadin antibody IgA -- all are negative results.  I noticed that I was not checked for TTG and Gliadin antibodies IgG and Anti-Endomysial IgG & IgA are also used for celiac disease diagnosis.  I'm not sure if these additional tests may diagnose celiac disease.  Are there are any other tests may diagnose this my "gassy" problem?

Based on my somewhat reduced protein level lately, I also wondered if it can be associated with some sort of mal absorption disease from small intestine.  Because I'm not mal nourished, now I'm trying to exercise and rebuild my lost muscle, so I'm taking sufficient amount of protein.  And my liver is not significantly damaged and should be able to produce sufficient amounts of protein.

Do you think  there is a  possible connection between mal absorption from small intestine -- to low Globulins -- Immunoglobulin production (even though, I understand that actual maturation of IgM &G occurs in bone marrow)?

Sorry for so many questions.
Thank you so much for all your help!!
(You already gave me peace of mind as possible recovering "shocked bone marrow" syndrome.

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Avatar_dr_m_tn
I am off to the Liver meeting in Boston, we can continue after I will be bvack.I basically think your bone marrow will gradually recover. The delicate balance of growth factors and cyrokine/receptor cross talk that determines these immune cell activities/ numbers tends to slowly normalize after a period of prolonged perturbation.
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Avatar_n_tn
First let me apologize for not getting back to you at the post from 10/22.
All these little emergencies with my husband keep me from responding in a timely manner.

I can't comment on your immunoglobulins because I don't know enough about them ( I leave that to HR ), but I can comment on gas problems and Celiac disease.

About 5 month post tx I developed enough gas to fly myself to Germany and back. I also developed
some cramping and intermittend diarrhea.
The connection between food and and these symptoms never crossed my mind. I had an iron stomach and no food allergies.
I had a bloodtest at Prometheus for inflammatory bowel disease including Celiac disease.
The results for Celiac came back neg but did not rule it out.
Antibodies for Crohn's disease came back mildly pos. ( You may remember that I developed Crohn's
6 weeks into tx ).
The doc ordered a small bowel study, which took close to 4 hours....drinking this nasty thick white stuff, and having an X-ray every 15 minutes as this chalk is moving through the jejunum.
Diagnosis....decrease of normal mucosal fold pattern and increased nodularity, suggestive of malabsorbtive process such as celiac sprue disease.

Needless to say, I almost fell of the chair. I had been eating wheat and gluten all my life without ill effects.
It took a week to sink in, but eventually I tried a gluten free diet with instant positive results.
Negative antibody tests for Celiac disease do not rule out this condition.
Many of us are born with a predisposition to Celiac disease ( or to any of the other auto immune diseases ), but only develop it under certain cicumstances. What are the circumstances....severe stress, chemotherapy, long illness......we surely fit the picture.
To make a long story short.....gas gone, cramps and diarrhea too, that is until this summer.
Back to hunting for more food allergies. Severe allergy to all soy products, fresh lemmon juice,and cherries.
Don't ask me what's going, I am the girl that used to fly from NYC to Las Vegas not to gamble, but to pig out on as many different foods as possible. Hubby gambled and pigged out, I only pigged out.

My gut is behaving now, for now.....haha until the next food allergy.

Does my long Interferon have anything to do with this.....NOOOO :))))

BTW, I have elevated Vit B12, over a thousand, normal Vit D, no osteoporosis, and below normal Vit A .
Does that fit the bill of a Celiac, nope. Does any doc no what the f***ck is going on, no.
Do I know what is going, no.
I do know that all this started post tx, and I expect there is more to come.

Hit the celiac sites, and you will see what people go through with related sides and illness until they discover they have are gluten intolerant.

I didn't know you tx so long....hey, you are encroaching on my record...I am the long distance runner here, that is after Lvdbygod, who tx 2 1/2 years.

Hope researcher comes back to you, he may need reminder.

All the best,
Ina

PS.... DHEA below normal for my age, and testosterone as well.
DHEA did not raise my testosterone as I had hoped, hence the testosterone cream.
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Avatar_f_tn
Dear Ina,
Thank you very much for your response.

I also never – ever had any food allergies!  My complete food tolerance has changed to who knows what… This is what my Dr. Mom said (Too bad, we have only long distance phone communications): no wheat and barley for me, she said that I should try buckwheat and rice instead.  And sure enough, after checking with Dr. Internet, I found out that wheat and barley have gluten and buckwheat and rice don’t have it.

Now, for a few days I didn’t touch wheat and barley, started taking the “beano” pills, but I’m still a very-very prolific carbon dioxide producing machine.  I guess, next step for me is to cut out completely garlic and onions from my diet, at least it will reduce amount of sulfa gas.

I used to laugh at Goofy Dad’s “colon dedicated” posts… well, I’m not laughing anymore.

I also suspect a mal absorption problem.  My lower blood-protein levels suggest it.  During my treatment, I had a hard time to maintain my weight.  At the beginning I dropped from 120 lbs to 110 lbs and my Dr. ordered, literally ordered to gain back weight or he would stop my treatment.  As a result, I relied my nutrients supply on liquid forms of protein, raw yokes, Ensure, and the rest was food whatever I felt like eating at the time … from junk sugary food to sweet fruits (such as grapes), or just regular meals, but I felt that regular food sort of just passes – through with this pale semi-digested color.

Also, I noticed, during treatment I could drink milk… if I stop consuming it for a little while and after restart drinking it, at the beginning I could have a mild diarrhea (or lactose intolerance), but by next day enzyme digesting lactose will be re-established and there will be no problems at all.  Now, I think my body permanently forgot how to digest lactose!
 Oh, I hope, nobody reads this thread before their lunch—

Now, when my appetite is back and I can enjoy all flavors, almost re-discovered my love for spicy food, garlic, and other stuff, I can eat it all without a single problem until it will reach my colon … I immediately get bloated, need to loosen my belt (this is why, I don’t like belts anymore!), turn on air freshener in my office, or run from other people’s offices in mid. sentence, or worry to death that I may have a “stinky” accident during next meeting.

Thank you, Ina, for sharing your experience … I guess I need to get serious about my digestion… I was hoping to investigate this problem with help of blood tests or other “non X-ray…ted” methods, but now I pretty much will anything just to get to the “bottom” of it!

If you could think of any more possible tests or blood tests, please let me know.

About vit. B12… I discovered that I have high vit. B12 levels in January 2007… when I noticed that I have “Terry” nails (whitish nail with a red band (~3mm) at the tip of the nail.  BTW, I still have Terry’s nails.)

My B12 concentrations were >2000.  I stopped taking my B-50 vitamins and at the end of May I had ~4600 (I asked a lab. to dilute my blood sample for a numeric value of B12 concentration).

My thoughts and prayers with you and your husband.  Hugs.
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Avatar_f_tn
HR,
Thank you very much for your valuable thoughts.  It is always greatly appreciated!

I checked history of my CBCs counts – in August – the same day when my IgM were noted slightly reduced to 29 -- total WBCs were 3.9k (~3.5 months post tx), in September (~4.3k), in October (~4.1k) – 10 days after October WBCs (~4.1) – immunoglobulins were measured and even lower IgM results were noted even lower (18), plus IgG was reduced to below lowest limit..  My Neutrophils fluctuated from 2.0k (August) to 2.6(September) to 2.2 (October).  Lymphocytes were at approximately the same level – 1.4k to 1.2 to 1.4k.

I guess, statistically speaking, I did not have any significant improvement – I was thinking that my WBCs were improving, but Immunoglobulin was decreasing.  I guess at this time all I can do is to relax and hope that with time my bone marrow will recuperate (hopefully!)

The same time I wondered if my “gassy” problems somehow were associated with a production of anti-anti bodies against my Immunoglobulin.  My understanding that if I test excessively positive for autoimmune anti bodies, my best treatment will involve intravenous Immunoglobulin injections … and this is something not really practical as a long term treatment.  Unless there are other possible treatments for this problem, I probably should not want to know if I have a problem (at least for a few months, hoping for my body’s resolution on its own).  Please correct me, if I’m wrong.

I would like to share with you my experiment with Oximatrine use.
I used it at the end of my treatment (hoping for increase of my blood platelets).  I don’t know about platelets, but it definitely was increasing my WBCs.  During my last few moths of treatment, I think, Oxymatrine helped me to reduce frequency of my Neupogen shots from 2 times weekly to every 5-6 days.  

I stopped taking Oxymatrine after about two weeks post treatment (at ~5/24/07) – my CBCs in July were low but okay for post treatment situation (I clearly remember that Neutrophils were increased to 1.7k) … but on August 6, my WBCs dropped even lower and Neutrophils reduced to 1.3k … I panicked and started taking Oximatrine again… one week later (on August 13), my WBCs were 4.5k with Neutrophils over 2k.  I explained it to my Dr. (general practitioner) and he didn’t believe me.  He stated that I don’t have any problems as far as low blood cells count.  He reluctantly agreed to give me monthly CBCs for follow ups.

After August 13, I didn’t take anymore Oximatrine.  I hope that my bone marrow in now working on its own.

On August 24, WBCs were measured 3.9k and Neutrophils 2k (this is when my low Immunoglobulin levels were discovered.  And after that, as I described to you above, my WBCs were measured at 4.3k (September 8-10) and at 4.1 (October 8).  Immunoglobulin further reductions were measured on October 18.  Today I’ll do one more CBCs … I’ll tell you my results.

I should note that RBCs are consistently 4.06 – 4.09 - 4.06 (during last ~3 months), but hemoglobin is normal (~12.8 – 13) – still slightly lower then pre-treatment.

Do you think my bone marrow is recovering?

Thank you very – very much for all your help!

All the best!
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Avatar_f_tn
My 11/05/07 CBCs results:

RBCs fell for the first time from 4.06-4.09 (during last at least 3 months) to 3.77k.

Hemoglobin - slightly reduced to 11.8 (still normal)
WBCs are looking good at 4.3k
Neutrophils are 2,232 (stable)
Lyphocytes are 1,591 (normal, used to be 1.2-1.4)
Platelets are 191 (higher and better than before).

I'm almost 6 months (5 days short) post tx.

Does it look as though my blood marrow is recovering?

Thank you very much for all your time and help!
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Avatar_n_tn
There is so much more to be said about Vit B12, stinkbombs that can not be held back :), food allergies in general etc. etc.
If you like, we can continue this off the forum, frankly some of the things I want to mention get a bit personal..
You can contact Foreseegood via her profile, and she can give you my e-mail and phone number, or you can leave your number with her, or just ask for my e-mail and then send me your number.
Some people here prefer to call me, but hesitate to give out their own number.
Whatever makes you feel comfortable is ok with me.

For the past 2 weeks I am having selected PC problems. I can receive e-mails, but can not send any.
Got this PC since 98, with the old windows 98, and desperately need to buy a new one.
Buying one is easy, transferring everything is a pain when you have little time.
I am not a big e-mail person anyhow, but a big jabber mouth on the phone.

In case you prefer to remain private, let me just tell you this.....don't rely on an endoscopy to give you the final verdict in regards to Celiac disease.
Celiac disease can affect the entire jejunum or parts of it, the distal duodenum or not at all. An endoscopy, even with an extension does not always reach the jejunum, either due to anatomical difficulties or the practioners inexpirience. So don't let anybody tell you they took a biopsy and it's neg. Doc here tried to tell me that too....in one ear and out....I said I want a small bowel study......but you don't have anything, you just have IBS.....when they don't know what a problem is, it's either IBS, Reflux, Menopause, Chronic fatigue or some other obscure nerve problem. Not that those conditions do not exist, just that docs like to use them as a "cop out dx", rather then saying "I don't know".
You can also have a stool test for fat.
Testing for food allergies is unreliable and a waste of money.
Cutting out wheat and barley is not enough. Gluten is in everything. Try a few days of a completely gluten free diet and see what happens.
After eliminating soy and lemon juice, I have been able to tolerate onions, garlic, and beans very well.
I am also not lactose intolerant, but still can't tolerate milk.

Beano contains gluten, hahaha....that stuff is in lipsticks, Vitamins, prescription drugs.
Before tx I would use Ambien for sleep occasionally, no problems.
During tx I could not tolerate it, never understood why. Of course at that time I didn't know that Ambien contained gluten, and that I was well on my way to develop gluten intolerance.
In the meantime Ambien has become gluten free and I am using it again.

Believe me, following a gluten free diet is a life changing event...travel, eating out etc. all become quite a bit more difficult.
You do know that Celiac is an auto immune disease.

Thank you for keeping me in your thoughts,
Best to you,
Ina
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Avatar_f_tn
Thank you, Ina!

I e-mailed to Forseegood.

Well I don't have right now any computer at home -- I'm usually using either from my work or our business' computer.

All the best,  always!
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Avatar_f_tn
I e-mailed to Forseegood ... again...

Thank you & have great holidays!
______________________________________
HR,

If you read, please give your imput.

Thank you very much!!
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Avatar_dr_m_tn
Wrote you a detailed reply yesterday, was lost due to password request.
In brief, after looking at the WBC/RBC  findings and the bigger picture, I think your bone marrow will recover from the IFN disturbances over time. But you need to follow up with your doc
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