Not injecting IVIG due to low IGA: Hi, after... - CLL Support

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Not injecting IVIG due to low IGA

ava1967ir profile image
30 Replies

Hi, after 9 days of fever, two negative PCR tests, and taking oral antibiotics, I had to be admitted to the hospital because my fever did not stop,

After intravenous injection of antibiotics in the hospital and numerous tests, to my surprise, my PCR test was positive….

The result of the antibody test was IGG: 300, IGA: 15 . I was not injected with IGVG according to the opinion of the hematologist, immunologist and infectious specialist. When I asked the reason, they answered because the IGA is low, there is a possibility of a negative and allergic reaction.... The treatment continued with intravenous antibiotics, intravenous dexamethasone, and finally 5 days of remdesivir. After 4 days, the fever stopped and I was finally discharged from the hospital after 10 days.

Treatment at home continues with oral antibiotics and prednisolone. So I am weak and lethargic.

Sorry, my text is too long, my question is, does anyone have the experience of not injecting IVIG due to low IGA? And do I with this immune system. Is it possible for me to have immunotherapy?

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AussieNeil profile image
AussieNeilAdministrator

I'm on a clinical trial so have had my immunoglobulins checked regularly (15 times) in the past 3 years. My IgA is very low, with results ranging from 5 to 15, averaging 11. My specialists have never mentioned any concern regarding this. I have subcutaneous IgG weekly, self administered. Boosting IgG via IVIG/subcutaneous IgG somewhat mitigates the increased risk of infection from having low IgA. (IgA plays a very important in reducing infection in the mucous membranes - respiratory system, gut, urogenital tracts.)

Neil

Vizilo profile image
Vizilo

Agree with Neil. I have also been SCIG for the last 2+ years with very low IgA. All the more reason to boost IgG

ava1967ir profile image
ava1967ir in reply to Vizilo

Thanks for reply🌺

SERVrider profile image
SERVrider in reply to Vizilo

I am the same as Vizilo, low IgA, low IgM and Low IgG. I have weekly SCIG and have no problems. Interesting, Neil that low IgA is associated with mucus and respiratory tract infections. That explains a lot.

AussieNeil profile image
AussieNeilAdministrator

I wonder if this study paper from 2012 is behind the decision by your hematologist, immunologist and infectious specialist?

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

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

"Serum IgG anti-IgA antibody has been associated with the development of adverse reactions, (including non-IgE mediated anaphylaxis) to intravenous immunoglobulin (IVIG) in patients with undetectable IgA (here defined as <7 mg/dL).1 Class-specific anti-IgA antibodies bind both IgA1 and IgA2; they are found in 25–30% of IgA-deficient individuals, but not in those with IgA> 7mg/dL.2 Subclass-specific (or limited specificity) anti-IgA reacts with only one subclass [IgA1, IgA2m(1) or IgA2m(2)].2 It is estimated that up to 40% of patients with selective IgA deficiency and 9–25% of patients with common variable immunodeficiency (CVID) may have IgG anti-IgA.3 IgE anti-IgA has been found much less frequently. Three of four patients with IgE anti-IgA had anaphylaxis to gammaglobulin or other blood products.4,5"

Of note, this situation is in respect to individuals who have low IgA because they have anti-IgA antibodies, that is, they make antibodies which destroy their IgA, which is why their IgA is low. With CLL, the primary cause of low immunoglobulins is due to the CLL suppressing plasma cell production of antibodies, not anti-IgA antibodies destroying their IgA.

Note the conclusion:-

"Given the rarity of anaphylaxis to IVIG, much larger prospective studies are required to establish more clearly any possibility of increased risk associated with IgA deficiency. It is not clear that class or sub-class specific IgG anti-IgA antibodies have clinical relevance. Our data and others' suggest that further study of a possible association is warranted. In an individual patient, the presence of IgG anti-IgA may indicate a need for closer monitoring, or consideration of alternative therapy such as SCIG, which appears to be tolerated in many of these patients."

I'll be very interested in the response of your hematologist, immunologist and infectious specialist when you ask them this question. Perhaps you can have subcutaneous IgG (SCIG) if they remain concerned? They could also test your IgG anti-IgA level to confirm that that's not responsible for your low IgA. Patient #23 was reported as having no problems in 2 1/2 years after switching to SCIG.

Neil

ava1967ir profile image
ava1967ir in reply to AussieNeil

Thanks ,for your detailed answer, I will definitely inform my hematologist about your answer in my next visit❤️🌺

SeymourB profile image
SeymourB in reply to AussieNeil

Neil -

I think most formulations of IgG actually contain some IgA, at least in the U.S.:

primaryimmune.org/sites/def...

They used to have a PDF Ig product chart. Now it's a Google Sheet:

docs.google.com/spreadsheet...

=seymour=

AussieNeil profile image
AussieNeilAdministrator in reply to SeymourB

The IgA is in negligible amounts though, around 1/500th the amount of IgG at best, from a quick look. :(

SeymourB profile image
SeymourB in reply to AussieNeil

Neil -

I believe the IgA content is a factor in adverse reactions, though. That's why Primary Immune posts the IgA content.

ncbi.nlm.nih.gov/books/NBK5...

Intravenous Immunoglobulin (IVIG) (STAT Pearls series)

Last Update: May 15, 2022.

"Severe anaphylactic reactions are rare and have been reported when using IVIG products due to the presence of IgG or IgE anti-IgA antibodies in patients with IgA deficiency.[79][80] Paradoxical use of IgA-depleted IVIG or a SCIG preparation is suggested in the treatment of patients with IgA deficiency.[81]"

As you noted, IgA deficiency itself a different cause of low IgA than CLL. They actually try to filter the IgA out. I think the resulting IgA is due to efficiency of the method used.

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

The Production Processes and Biological Effects of Intravenous Immunoglobulin

Published online 2016 Mar 9

"The implementation of chromatographic procedures also aims at the removal of IgA, a cause of severe anaphylactic shock in patients with IgA deficiency presenting anti-IgA antibodies."

=seymour=

ava1967ir profile image
ava1967ir in reply to AussieNeil

H I Neil, yesterday I was visited by an infectious disease specialist due to the continued cough, weakness and malaise, and he said that my fever and blood oxygen should be checked, and due to my weak immune system, the covid test should be done after 21 days (10 days later).I asked about IvIg injection. The answer is that the oncologist should make a decision after the partial recovery. I was W &W for 10 years, and due to the drop in platelets and hemoglobin in the past year and the spleen was very large, in August, my oncologist again gave a bone marrow biopsy and was treated with start ibrutinib……

In the coming weeks, after recovering from Covid, I will definitely share your scientific opinion about IVIg injection with my oncologist

and I will share the result with you

Thanks & Regards 🌺

Panz profile image
Panz

My experience is my IgA is usually 3 or 4 never above 5; my IgM is generally 10 and my IgD is zero and they have stopped testing for that as it involves a separate special test that has to be sent out and it had been zero for years. I have IVIG every 4 weeks and will the rest of my life and it keeps me in a very safe place!!!!

All the best to you….I am hoping you get this sorted out soon!

Panz 🙏🙂💕☘️

Aerobobcat profile image
Aerobobcat in reply to Panz

Hi Panz, I too have been having 3 weekly IVIG infusions for over 8 years now. I like many of you have low IgA and IgM levels. Can you advise me what level your IgG levels are? Mine are now within range and the doctors are suggesting that they may now stop the infusions as we have a shortage within the UK.

kaymack profile image
kaymack

My IgA is 0.2 g/L (ref. Range 0.4 - 4.0). I am now having weekly SC IgG infusions, also. My Immunologist says boosting my IgG will help mitigate my low IgA levels.

I contracted an RSV pneumonia four years ago. I was not given IVIg at the time, and I developed Bronchiectasis, and now live with a chronic productive cough. The Bronchiectasis prompted the start of the IVIg infusions. A respiratory specialist tells me, if I had been given IVIg when I came down with the pneumonia, I wouldn't have developed the Bronchiectasis.

Aerobobcat profile image
Aerobobcat in reply to kaymack

Hi Kaymack, I too have bronchiectasis and low IgA and IgM with in range IgG. Its interesting to note your immunologist say’s boosting your IgG will help mitigate your low IgA when my doctors are suggesting they may stop my infusions as my IgG is now in range even though I still have low IgA. I am confused!!

AussieNeil profile image
AussieNeilAdministrator in reply to Aerobobcat

Only your IgG count is involved in the approval process for IgG infusions. Because getting your IgG to an acceptable level helps compensate for low IgA, the IgA count isn't considered relevant. That might change when IgA infusions become possible.

Neil

Justasheet1 profile image
Justasheet1 in reply to AussieNeil

Neil,

Are they working on the possibility of IGA infusions?

Jeff

AussieNeil profile image
AussieNeilAdministrator in reply to Justasheet1

The manufacturer of Hizentra was working on an IgA infusion product a couple of years ago and seemed fairly confident about it.

bayside64 profile image
bayside64 in reply to AussieNeil

Does 400 IGG qualify for IVIG infusion? At 299, I was given 1/2 dose. My appointment with my specialist is next week.

AussieNeil profile image
AussieNeilAdministrator in reply to bayside64

To qualify for IgG boosting, you need to meet two criteria:-

1) Recent serious infection(s), e.g. requiring hospitalisation for IV antibiotic treatment

2) IgG below a specified threshold, which varies by country (and in the US, I gather by state and/or health insurance). The threshold can be as high as 500 in some cases in the USA, but 400 is more typical. It's the threshold in Australia and I think now the UK.

IgG is roughly as expensive as gold by weight as it is in limited supply, determined by blood/plasma donations. To provide good infection prevention coverage, a batch is made from the pooled donations of at least 1,000 donors. IgG for IVIG use has been in short supply since around 2018 or so with the pandemic only worsening the situation, so naturally the criteria become harder to meet to manage the supply shortage. Subcutaneous IgG (SCIG) is a new product line for suppliers and hence supply shortages don't seem to have been an issue - you don't want to dissuade new customers from what is a better way to keep antibody based immunity topped up. Unfortunately, in the US, access to subcutaneous IgG depends on your insurance, with some companies/plans approving IVIG, but not SCIG. Doesn't make sense to me, as with SCIG, you don't need the expense of nurses trained in providing and managing infusions and you avoid the infection risk associated with travelling to and attending a medical facility.

See:

healthunlocked.com/cllsuppo...

healthunlocked.com/cllsuppo...

Of relevance, cancer patients are the largest patient group dependent on blood donations, so when anyone asks what they can do to help you, ask them to become a blood donor.

Neil

bayside64 profile image
bayside64 in reply to AussieNeil

Thanks so much for your response. I was on IVIG for 24 months. My new CLL specialist said I didn’t need it. My test from last week was at 400. I will see him next week.

kaymack profile image
kaymack in reply to AussieNeil

I'm in NZ. Pooled plasma from NZ donors is sent to CSL in Australia to be processed into SC and IV IgG. My SC IgG is branded Evogam.

Aerobobcat profile image
Aerobobcat in reply to AussieNeil

Many thanks Neil for your response your Knowledge is always welcome

Newdawn profile image
NewdawnAdministrator in reply to Aerobobcat

I had IVIG for 12 months when my IgG was nudging 4 but it had no positive impact on my other levels at all. My IgA & IgM are nearly off the bottom of the scale. I’ve always understood that only IgG could be supplemented and it almost acts as a kind of surrogate safety net for the other levels. However, IVIG doesn't supplement or restore the other levels. Just helps to prevent the major infections. I honestly don’t know to what extent it can ‘mitigate’ low IgA levels but they won’t give infusions on the basis of this.

Newdawn

Aerobobcat profile image
Aerobobcat in reply to Newdawn

Many thanks Newdawn for your response and as with Neil your knowledge is always appreciated

kaymack profile image
kaymack in reply to Aerobobcat

My IgG level was 0.7 g/L (ref. range 7.0 - 16.0) before I started receiving IV1g. Now after several years of receiving IVIg, it was 8 at last blood test.

My IgA is currently 0.2 g/L (ref. range 0.8 - 4.0) and my IgM is 0.2 g/L (ref. range 0.4 - 2.5). Those numbers have not budged in many years. I had FCR treatment during 2013 and have been in remission since. My Igs were low prior to treatment, and dropped even lower after treatment.

Historically, many haematologists only commenced IVIg in someone with hypogammaglobulinemia, if they had 3 major infections over a period of one year.

I suspect my Immunogist's comment about mitigation was in regards to the severity of infections. I have had an ORL specialist say he didn't think I would benefit from sinus surgery due to my low IgA levels (IgA circulates in mucous membrane). My Respiratory Specialist has me on long term Azithromycin 3x week for my bronchiectasis. I suspect that has prevented sinus infections, also.

Aerobobcat profile image
Aerobobcat in reply to kaymack

Hi Kaymack, I can identify with so much of your CLL experience. I do realise now why I have been on IVIG for so long, now entering my 9th year, clearly as a result of being hospitalised 15 times with chest infections and 4 with sepsis.

Feel better, thinking of you!!

Aerobobcat profile image
Aerobobcat in reply to

Thank you Cookie

wmay13241 profile image
wmay13241

CAR-T permanently damaged my wife's bone marrow. Her IgA is less than 5 and her IgM is less than 25. She has had bimonthly IgG Gamunex-C infusions every 2-3 months since 2016 - no infusion reactions or side effects. And no infections!

skipro profile image
skipro

It is NOT possible to replace IgA and a large percentage of CLL patients have no or low IgA, M and G. I get regular IgG infusions and have barely detectable IgA and M.

The IgG protects from serious bacterial infections, and typically, there are a lot of covid antibodies both from vaccinated or previously infected donors.

I'd push for IgG. In fact, many centers give high dose IgG to CLL patients with Covid.

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