IGIV/SCIG and Low IgA

[Jungle-Jim]

This is a follow-up question re: IGIV therapy. My IgG dropped from 451 to 383 in 17 months. My IgA level dropped from 27 to 17 during the same period. I've read that IGIV/SCIG therapy is not administered when IgA is low. Is that true in all cases? If so, are there alternative treatments? This is yet another serious concern and informed opinions are welcomed! I'll see the oncologist on October 13. Thanks!

[lankisterguy Volunteer]

Hi Jungle-Jim,-

I recall that IVIG is used to supplement low IgG, but there are no currently available treatments to supplement or raise IgA or IgM.

-

These links may help explain ( they are for Selective IgA deficiency) :

mayoclinic.org/diseases-con...

-

primaryimmune.org/about-pri...

SNIP It is not currently possible to replace IgA in patients with IgA deficiency, although research toward purification of human IgA is ongoing. However, it remains to be seen if replacement of IgA by any route (IV, oral or topical) will be beneficial for humans with IgA deficiency, in part because IgA in the serum, unlike IgG, does not remain in the circulation for very long.

Treatment of the complications associated with Selective IgA Deficiency should be directed toward the particular problem. For example, patients with chronic or recurrent infections need appropriate antibiotics. Ideally, antibiotic therapy should be targeted at the specific organism causing the infection. Unfortunately, it is not always possible to identify these organisms and their antibiotic sensitivities precisely, and the use of broad-spectrum antibiotics may be necessary.

-

In my own case I have normal IgG levels but IgA and IgM levels below normal. I have had almost no infections in the last 10 years, but I am also very careful about sanitation and exposure to sick relatives.

-

Len

Immunoglobulins

[Newdawn Administrator]

Ive not heard this Jim and it certainly wasn’t a consideration for IVIG when I started it. My IgA was .42 (normal range should be 60-100) so severely depleted. My IgG was about 4.2. Sadly my IgA and IgM have continued to decline but the immunoglobulin infusions only supplement the IgG as Len has said.

Newdawn

[Jungle-Jim in reply to Newdawn]

Thank you Lankisterguy and Newdawn. As I understand it, there are no treatments for IgA deficiency - it is a permanent problem with respect to fighting infection(s).

But I'm concerned (based on what I've read on numerous sites) that oncology will not prescribe IGIV/SCIG if you have low IgA. My IgG has plunged from 451 mg/dl 383 mg/dl. I was hoping that therapy might help me later on as the disease progresses (I appear to be an imminent candidate), but I fear that hope may evaporate.

Question: Has anyone with low IgA (as stated, mine is 17 mg/dl and falling) been allowed to receive IGIV/SCIG therapy? Thanks in advance!

[Newdawn Administrator in reply to Jungle-Jim]

My answer is yes because I was given IVIG and frankly have not heard of this exclusion. However I’m in the U.K. but I’ve not heard of this reference to low IgA in any of the clinical eligibility criteria for infusions.

I’d too be interested if anyone else has been refused because generally hypogammaglobulinaemia resulting in IVIG/SCIG is usually a deficit across all immunoglobulins. Can you link to where you read of this issue with IgA affecting eligibility please Jim.

Newdawn

[Jungle-Jim in reply to Newdawn]

Hi Newdawn:

As I understand it, "Selective" IgA Deficiency means your IgG is NORMAL, but your IgA is DEFICIENT (e.g. "selective"). In my case, IgA, IgG and IgM are all below the "normal" threshhold.

I looked at several sites, and lo and behold, the emphasis seems to be on SELECTIVE IgA deficiency. One such site is here: primaryimmune.org/about-pri...

While I seem to recall others, the only site I see today that seems to address IGIV and 'regular' IgA deficiency is here: versusarthritis.org/about-a...

So, I'm back to being confused again... it may be that I've 'jumped the gun." So, I'm hoping there is a member of our group who is an MD who can shed some light on this.

[HopeME in reply to Jungle-Jim]

My IgG and IgA are both deficient although the last time my IgA was checked it was less deficient than my IgG. My understanding is that there is nothing that can be done to replenish IgA even on a temporary basis but improving IgG is possible with recurrent and ongoing IVIG or SCIG. I believe improving IgG in the bloodstream goes a long way to reducing infections and can compensate to some extent for low IgA which is typically found in mucus. I also believe it is common to have all of the immunoglobulin categories deficient but I’m not 100% certain on that point.

Thanks

Mark

[Jungle-Jim in reply to HopeME]

Thank you Mark, that's my understanding too. My knees buckled when I read contrary statements about prescribing IGIV and low IgA. Again, I'm hoping to treat the low IgG (when the doc prescribes it)... but I realize the low IgA is a lost cause.

[Newdawn Administrator]

Jim, you’re confusing very different conditions here.

Immunoglobulin A (IgA) deficiency is a common primary immunodeficiency characterized by undetectable serum IgA, a concomitant lack of secretory IgA, and normal levels of other immunoglobulins. IgA deficiency should be distinguished from any other cause of hypogammaglobulinemia or T lymphocyte defect.

We develop an acquired immune deficiency as the result of CLL and Immunoglobulin A (IgA) deficiency is ‘a common primary immunodeficiency characterized by undetectable serum IgA, a concomitant lack of secretory IgA, and normal levels of other immunoglobulins.’ IgA deficiency should be distinguished from any other cause of hypogammaglobulinemia or T lymphocyte defect. The latter is what we get due to our B-cell–related malignancies. We acquire our depleted immunoglobulins, it’s not a congenital condition.

Clearly people with a primary immunodeficiency of IgA could have other normal immunoglobulins which is why you will have read that they are not offered IVIG. They don’t need their IgG supplementing. They are not usually blood cancer patients.

This is my understanding and there’s no reason why our acquired hypogammaglobulinaemia should prevent us from receiving IVIG if our IgG is low (usually under 4) regardless of what our IgA is.

rarediseases.org/rare-disea...

Hope that makes sense. Bottom line is your levels probably qualify you for IVIG because your IgG is sub-optimal. If it was normal and only your IgA was severely affected, you’d be suffering from a very different immune condition.

Newdawn

[Jungle-Jim in reply to Newdawn]

This isn't the first time... nor will it be the last... that I find myself "up to my armpits" in muck as I try to navigate this journey. There are so many nuances associated with CLL and I'm becoming increasingly convinced that I should tread carefully in trying to do any of my own research.

I hope you're correct Newdawn (and I suspect you are) - it would be nice to know that there is a treatment (IVIG/SCIG) that may help my immunodeficiency situation... and that I would be eligible to receive it. This of course applies to the others in our group as well. Thanks Very Much!!!

[Newdawn Administrator in reply to Jungle-Jim]

It’s confusing stuff if we delve too deep into the intricacies of the human immune condition Jim. My immunoglobulins/antibodies have been dropping across the board since I developed CLL. Only thing to help is IVIG which supplements only the IgG but helps the others (they believe). Somebody presenting with only a severely depleted IgA has a very different immune profile not connected to our situation. You don’t need to worry about it because the medics won’t. They’ll only concentrate on your IgG.

Go get your IVIG or sub cut method. It really can help. Sadly the NHS no longer can offer me them ☹️

Newdawn

[HopeME in reply to Newdawn]

Hi Newdawn:

Thanks for your excellent analysis of Jungle-Jim’s questions. You are an excellent communicator as evidenced by your ability to decipher complex CLL topics, break them down and write about them so clearly. The one thing I don’t understand is why can’t you get IVIG? I know others in the UK are receiving this therapy but you aren’t despite the fact you have had previous serious infections and you have below range IgG. Aren’t those the only criteria that need to be met? I certainly hope you are able to get back to receiving periodic infusions soon. It isn’t fair that you are being excluded.

Best,

Mark

[Newdawn Administrator in reply to HopeME]

Many thanks. I was receiving IVIG which started the same day as my I&V treatment Mark. I had them monthly for a year and all was going well. When lockdown occurred, they naturally didn’t want patients in the day-unit and lo and behold I was told I no longer met the reviewed criteria for access to IVIG. It now required a IgG under 4 and frequent infections. As I’d been receiving monthly infusions, I’d dodged recurring infections and my IgG was just over 4. I was also told availability and cost on the NHS affected this decision. I objected but I’m afraid it ‘fell on deaf ears’. The Consultant told me that he now had to offer prophylactic antibiotics as a first precautionary treatment due to cost. I was already on co-trimoxazole and during this recent respiratory tract infection, I think they have helped.

I’m monitoring my situation and will certainly push for them if I start to suffer recurring infections again.

Regards,

Newdawn

[HopeME in reply to Newdawn]

I think I understand now. The required IgG level has been dropped by 20% (5 to 4) irregardless of recurring infections? That seems a bit dangerous but at least you have prophylactic antibiotics to help protect you and if yourIgG level falls beneath 4 (hopefully this won’t happen) you can restart IVIG. The last my IgG was checked in March 2021 it was at 5.3 and no significant infections yet, thankfully. I am hoping I stabilize at this level and and continue to avoid infections. I do have a bag packed on your advice in case I ever need to leave quickly for the hospital.

Enjoy the rest of your evening,

Mark

[Jungle-Jim in reply to HopeME]

I understand that protocols have to be in place for a number of reasons. Still, I agree with Mark - it's a shame that you're currently not eligible. I have a feeling that your status will change in the future and treatment will be restored (at least I hope so). Thanks again to everyone who enlightened me on this subject with your valued responses!

[Wiganmc in reply to Newdawn]

Sorry for not posting (only responding) after telephone consultation with a locum consultant he said privigen infusions to be every 6 weeks as apposed to every 4 weeks, with a view to every 8 weeks ig 5.2 this after 3 years of treatment, in the follow up letter he says he has discussed this with me and I'm happy about this, at no point in the conversation did I say I was happy about this move, he also goes on to say if 8 weekly infusions a success with limited infections "I would be given a break from infusions in the summer periods, this was never discussed at all, my faith in the medical fraternity is certainly waning I also understand the process of producing the said privigen eg time/cost I feel there is other reasons that we are not being told about, goalposts being changed all the time, although I am in remission at the moment I don't think changing any of my treatment at the moment is such a good idea, and don't tell porkies to justify. Rant now over thanks for reading I will update.. Stay safe Tony

[Jungle-Jim in reply to Wiganmc]

Thanks Tony - I'm beginning to think there are others who share your frustration. I'm reminded of the old expression... "if it ain't broke, don't fix it." One can only assume your medical providers have sound reasons for changing the rules in the middle of the game. I've only been in a W&W status for 1 1/2 years (as I've watched numerous adverse trends in my blood work), and can't help but wonder what the future holds in store for myself and other CLL sojourners.

[Jungle-Jim in reply to Newdawn]

I'm sorry to hear of your current status. But, I have a feeling that it will change in the future and treatment will be restored (at least I hope so). Thanks again for your responses! Jim

[AussieNeil Partner Administrator in reply to Jungle-Jim]

Interesting, clarifying discussion. I hope that you have also appreciated that serious infections are also a very important part of the criteria in determining if IgG infusions are required. IgG is a finite and currently scarce resource. IgG counts are made up of millions of different immunoglobulins. How well we fend off infections depends on us both having adequate immunoglobulins specific to the infectious diseases we are encountering and having an immune system that responds to the invaders targeted by our immunoglobulins. It's possible for some to have a very low IgG count, yet stay in good health, while others with higher IgG counts struggle with frequent infections.

Neil

[Jungle-Jim in reply to AussieNeil]

Thanks Neil.

[wmay13241]

Untrue for us. Since her CAR-T infusion in 2016, my wife (74) has received an Gamunex-C IVIG infusion every 2-3 months when her IgG drops below 400 - her IgA and IgM levels are both <5. I am not aware of any treatment for either low IgA or low IgM.

[Jungle-Jim in reply to wmay13241]

Thank you wmay - as stated, I know there is no treatment for IgA deficiency. I had (mistakenly) understood that IGIV would not be administered if IgA is low. I was confounded by different Web sites that published contrary statements re: the administration of IGIV. I've since been enlightened by contributors to this forum and am now "at peace" over the issue. Best wishes to your wife!

[SeymourB in reply to Jungle-Jim]

Jungle-Jim -

I agree with NewDawn's analysis. Some papers do not use the word "selective" before IgA deficiency. What we have is hypogammaglobulinemia (that's a great Scrabble word!), and not a selective deficiency.

Some Ig products do indeed contain small amounts of IgA. The site, PrimaryImmune.org has an abundance of info on Ig products, because they serve a community that has congenitally low IgG.

primaryimmune.org/sites/def...

I think they list IgA content for products, because IgA content in Ig serum is thought to be more likely to cause infusion reactions:

ncbi.nlm.nih.gov/pmc/articl...

Association of anti-IgA antibodies with adverse reactions to gamma globulin infusion

But it seems to be controversial:

pubmed.ncbi.nlm.nih.gov/218...

The role of anti-IgA antibodies in causing adverse reactions to gamma globulin infusion in immunodeficient patients: a comprehensive review of the literature

(Abstract only - behind paywall)

There is indeed an Ig product that contains significant IgM and IgA - it's called Pentaglobin.

transmedpharma.com/our_prod...

I'm not sure who manufactures it. It's apparently used for short term care in the case of severe infections, such as sepsis.

It's been around for a few years, and there have been several trials:

clinicaltrials.gov/ct2/resu...

Some references I've seen call it IVIGAM, and others IVIGMA. As bad off as we are, I don't think we ever want to get into a situation requiring Pentaglobin.

In any case, nothing we can do for our low IgA and IgM yet that I've heard. I'm low on all 3, and slowly getting lower.

I think the best we can do for IgA is to test our vitamin D3, and supplement if needed, and wear a well fitting N95, KN95, or FFP2 mask to protect our nasal mucosa when among people outside our household. Buy such masks from the manufacturer if you can - there are many counterfeits around on Amazon, eBay, Etsy and similar unregulated market places.

=seymour=

[Jungle-Jim in reply to SeymourB]

Thank you very much for your detailed response Seymour - you, Newdawn and the others have cleared away the fog and I now feel extremely enlightened. Y'all's inputs affirm the purpose and value of this forum! Blessings!

[Jungle-Jim in reply to SeymourB]

BTW SeymourB, I was an ST1 in the USCG, and went on to retire as a full Commander (22 years). I'm also a HAM (ag4nm), but haven't been active for a while.

[SeymourB in reply to Jungle-Jim]

I was an ET2 in the USCG back in the late 70s, in case anyone else is reading along. ham call sign KE5JUR, also not very active unless the power goes out for days because of a storm. I ran the ham station at a hospital in the years after hurricane Katrina. But we've been lucky in the immedeiate vicinity of New Orleans since then, and the airwaves are quieter.

=seymour=