Iga and Igg subclass deficient

[jack9149]

Hi

I have been diagnosed with Iga deficiency (pretty much zero) and Igg subclass deficiency

My immunologist says that IVIG is not really an option for me, as my body may react very negatively to the trace levels of Iga in the IVIG. He says it is virtually impossible to find Iga deficient IVIG.

I am new to all this, so I'm not sure if the above situation is common or not, and whether it means IVIG really is a non-starter, or whether people in my situation sometimes have to take it despite the risk.

Any input v welcome.

best regards
Jack

[s162216]

Hi Jack and welcome to the forum,

I'm not too sure why your immunologist would say that IVIG is not an option. Most people who have CVID for instance have IgA deficiency as well as part of the condition, yet that would then mean of course that they would not be able to have IVIG either, when its the standard treatment for most!

The actual problem is not the IgA deficiency itself, but in some IgA deficient people the body expresses anti-IgA antibodies against IgA, and in theory this can lead to reactions when having IVIG. Has your immunologist checked you for anti-IgA antibodies as you won't have a problem if you don't?
The actual risk is not really known, and is viewed as more of a 'precaution' nowadays: quite a few years ago it was noted that some patients who had anaphylaxis type reactions expressed anti-IgA antibodies. The problem really is that such reactions can (very rarely just reassure you) occur in anyone having IVIG, and its of course impossible to know whether the anti-IgA antibodies actually caused the reactions or not. Generally today most immunology staff that I have talked with view it as more of 'theoretical risk', and more recent research has suggested that the concern over it was probably an over-reaction.

There are several very very low IgA IVIG preparations out there, and generally the level is much lower anyway compared to even 10 years ago due to advances in the purification, filtering etc. I myself have nearly unrecordable IgA (less than the assay can read to!) and express anti-IgA antibodies; I've not had any severe reactions from having IVIG for the past nearly 4 years (I do get headaches sometimes after having it, but their quite common in most people having IVIG). The type I use is fairly low in IgA (about the same as most are these days with some being a little lower/higher), and suits me best as it's one of the few which doesn't use a sugar based preservative (I'm a type 1 diabetic so obviously a sugar based one could be a bit problematic!).

I don't know where your from, but I have noticed that in the US they seem to be much more concerned about anti-IgA antibodies than over here in the UK so I don't know if its more of a 'country specific' or 'medical culture' based concern. Perhaps their just more concerned about getting sued!

Hope you find this helpful,

Sam

[jack9149]

Hi Sam,

Thank you very much for your quick and helpful reply.

My immunologist has not checked me for anti-IgA antibodies. I spoke briefly with him today - he has a view that even if I don't have them now, I am likely to develop the anti-igA antibodies after the first few IVIG. He does not seem very enthusiastic about IVIG for me, but perhaps he feels that the frequency and severity of my infections does not warrant IVIG yet. I've had pneumonia each year for the past 5 years, and needed hospital treatment twice. I know from reading forums online that some people suffer a lot worse.

Anyway your input has helped me understand that IVIG is perfectly possible for someone in my situation (in fact relatively common). So, thank you for your advice and I'll continue to learn more so that I can make the best decision in due course, and I hope to continue participating in this forum in a way that is helpful to everyone.

I am in Hong Kong btw. 

best regards
Jack

[s162216]

Hi Jack,

I'm happy that I've managed to be of help! (The following is just speculation from what I know of immunology through my Pharmacology degree) Your immunologist may not think the IVIG is worth it because from what I can remember of IgG subclasses, the actual half life of each type does vary greatly. If I remember the IgG1 subclass has the longest half life of about 21 days, but the IgG3 subclass has the shortest at only 6 days. Because of that if your deficient in the class with the shortest half life then it may not be worth it, although subcutaneous IgG may be of more help because its given every week compared to every 3 - 4 with IVIG. I'll look up the subclasses in my copy of Janeway's Immunobiology and read up on it again.

I've never had pneumonia or any other serious infections apart from once, but I did used to get a few more infections per year than I should have really (I have CVID and am quite deficient in all IgG subclasses, have nearly no IgA and am a bit deficient in IgM). As so they decided to start me on IVIG immediately, and it has been a great help as its cut down the amount of infections I get to 2-3 at the most each year. I was probably lucky though as I got detected much earlier than most, which means I'll be better prepared if I ever get worst (unfortunately CVID has a habit in patients of not showing hardly any symptoms for years, and then suddenly everything goes downhill).

I'm quite interested in how immunology services are run in different countries, and was just wondering what their like in Hong Kong (somewhere I would love to go one day!)?

Thanks,

Sam

[aryani]

Hi,

I have been hesitant to react on this post. After all, I am not a doctor. And more important, I don't want to trivialize your health-complaints. I am not sure that my English is good enough to put it all in the right words.

I agree with Sam about the anti-IgA antibodies. It is a reason to start slowly and it is also a reason to start in a hospital.
Sam's remarks sound logical, but a lot of patient with CVID are receiving IVIG and are deficient in all subclasses. Most people I know are on IVIG and not on subcutaneous. So, that leaves me confused.

I know of a few other reasons why doctor's can be resistant to prescribe IVIG. Being a blood product, there is always a very small risk of transferring nasty things. It is also quite expensive, compared to a daily dose of antibiotics. Popping a pill a day is so much easier than IVIG and takes less time. It is also not common practise to prescribe IVIG in the case of IgG-subclass deficiency. Taken these factor's into account, it can be why your doctor is resistant prescribing IVIG. Having written all that, I hope you will get proper treatment, whether that is IVIG or something else.

Aryani.

[s162216]

Mar 24, 2014 5:32:40 GMT aryani said:

Hi,

I agree with Sam about the anti-IgA antibodies. It is a reason to start slowly and it is also a reason to start in a hospital.
Sam's remarks sound logical, but a lot of patient with CVID are receiving IVIG and are deficient in all subclasses. Most people I know are on IVIG and not on subcutaneous. So, that leaves me confused.

IVIG is unfortunately not ideal as following each infusion the plasma level of each IgG subclass falls exponentially, but obviously each subclass has its own half life. According to my copy of Janeway's Immunobiology the following halflifes apply to each subclass:

• IgG1: 21 days (Adult serum level ~9 mg/ml)
• IgG2: 20 days (Adult serum level ~3 mg/ml)
• IgG3: 7 days (Adult serum level ~1 mg/ml)
• IgG4: 20 days (Adult serum level ~0.5 mg/ml)

So in reality its only the IgG3 subclass which is shorter, and normally it has the second lowest level in serum anyway (because of this IgG preparations usually contain the 2nd lowest amount of that as well out of the other IgG subclasses).

Because of the smaller, more frequent dose nature of subcutaneous dosing, it allows the plasma IgG levels to remain inside a much more constant range than IVIG. With IVIG plasma IgG levels fall exponentially which means they are usually at their lowest by the time of the next infusion (and then theres a 'spike' from having the next infusion and the cycle repeates) which can make some patients more prone to infection then. SCIG levels also fall exponentially, but because each infusion is every week you don't get the massive 'peaks and troughs' like with IVIG to as great an extent so the IgG levels remain much more constant. I'll try and find a suitable picture to illustrate what I mean (its just basic pharmacokinetics which was a subject I was quite good at at university!)

SCIG is not for everyone, I have IVIG as I don't get any problems with it, and also I don't have very much subcutaneous fat (and what I do have I use for my subcutaneous insulin pump which I have attached to me all the time).

I hope that clears up any confusion,

Sam

[aryani]

Hi Sam,

Thanks for clearing that up.

Aryani.

[jack9149]

I have re-checked with my Dr, and I am deficient in IGg2 and IGg4, so I gather that's a positive in the sense that, should i need to move to IVIG at some stage, my subclasses have a decent half-life (i.e. iGg3 is not my issue)

Anyway Spring is finally here in my part of the world (Hong Kong) and I usually have an infection free summer, so here's hoping I will have plenty of time to ponder the options !

Thanks Sam and Aryani

Jack

[s162216]

At least thats somewhat good news Jack, its when the IgG1 is deficient that the major problems can start as obviously thats the most abundant in the body. I hope that things go alright for you, and you get the infection free summer you desire (at least you'll get better weather than here - in the UK all we've been getting for months is rain, rain and more rain!).

Sam