IgA-deficiency - blood transfusion

[Phloston]

In pts with IgA-deficiency, a percentage develop IgG antibodies against IgA, such that if they receive blood transfusions from non-IgA-deficient pts (i.e. most people), they experience anaphylaxis.

UWorld says the above.

My question is: normally epinephrine is the Tx for anaphylaxis; with respect to the above, would it be safe to say that this is anaphylaxis due to a type-III hypersensitivity reaction? For some reason, I had had the impression that anaphylaxis, if immunological, needs to be type-I hypersensitivity-induced.

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[mayn]

Apparently, a person with IgA deficiency can develop either IgG, OR IgE antibodies against IgA (though apparently there is controversy over IgE can be present or not)

If the person has IgG antibodies, then complement system is activated with the various anaphylatoxins generated (C3a, C4a, C5a,), leading to ultimate anaphylaxis.

If the person has IgE antibodies, then that's the regular anaphylaxis reaction (Fab of IgE bind to IgA, cross link, and degranulate the mast cell).

The IgE anti-IgA is definitely type 1HS, and I would presume the IgG anti-IgA is type 3 HS (like you suggested).

Treatment in both cases would be standard, i.e epinephrine, bronchodilators etc

Good question man, had me googling for 10-15 minutes lol.

Here's what found:
http://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/8154 <= for IgG
http://www.transfusionmedicine.ca/book/export/html/246 <== for IgE

 

[Phloston]

I guess I just don't fully understand. How is the complement activation with the IgG-IgA interaction actually causing the anaphylaxis? I would think that the Ag-Ab complexes would lodge in the blood vessel walls, then bind complement, leading to neutrophil recruitment and subsequent inflammation.

Does the latter sound right? (my immuno sucks)

 

[mayn]

Actually, now that I think about it.. if its mediated by IgG antibodies, then its not really a hypersensitivity reaction at all.

So as far as I understand it: the IgG binds to the new found IgA, and this will activate the classic complement system, generating in particular C3a, C5a.. which can then directly degranulate the mast cells, leading to anaphylaxis.

So then the question would be, why dosen't everyone who has a type 3 HS suddenly undergo anaphylaxis? I am not sure.. maybe the amount of immune complexes?

 

[Phloston]

Actually, now that I think about it.. if its mediated by IgG antibodies, then its not really a hypersensitivity reaction at all.

So as far as I understand it: the IgG binds to the new found IgA, and this will activate the classic complement system, generating in particular C3a, C5a.. which can then directly degranulate the mast cells, leading to anaphylaxis.

So then the question would be, why dosen't everyone who has a type 3 HS suddenly undergo anaphylaxis? I am not sure.. maybe the amount of immune complexes?

Yeah, but the donor IgA would be the antigen and the endogenous anti-IgA IgG would be the antibody, so the immune complex formation inducing a clinical immune response would have to be considered a type-III hypersensitivity. Unless I'm just on crack.

I'm still not getting it though. What do you mean the complement "then directly degranulate mast cells"? What's the actual mechanism?

 

[mayn]

Well C3a, C4a, C5a are all anaphylatoxins. They can trigger anaphylaxis, by directly degranulating a mast cell, without any IgE involved. I am not sure of the exact mechanism though, that's as far kaplan immuno went into it.

With regards to the hypersensitivity.. yes antigen-antibody complex would be a type 3 HS.. I was just thinking aloud lol and assumed since its IgG leading to anaphylaxis, it wouldn't be a 'hypersensitivity' per se. (because anaphylaxis really isn't much of a feature of type 3 HS).
That's why I asked how come there isn't a anaphylactic reaction in say.. SLE, or PAN, or early rheumatoid arthritis, which are all systemic type 3 hypersensitivities.

Dunno.. maybe I just need sleep.

 

[Phloston]

Unless I'm just on crack.

Well C3a, C4a, C5a are all anaphylatoxins.

See, I am apparently on crack. As Goljan would say:

I mean duhhhhhh

Yeah, C3a/C4a/C5a are the anaphylatoxins. Not to mention, that's also right in FA. Good one, Phloston.

 

[mayn]

See, I am apparently on crack. As Goljan would say:



Yeah, C3a/C4a/C5a are the anaphylatoxins. Not to mention, that's also right in FA. Good one, Phloston.

lol.. happens to the best of us

 

[Charles_Carmichael]

I'm confused as well. Pholston, just like you, I was under the impression that, when discussing anaphylaxis, we're referring to an IgE-mediated, type I hypersensitivity reaction.

Why would a type III reaction lead to anaphylaxis? I understand that activation of complement will lead to production of the anaphylatoxins, which can induce mast cell degranulation. But why don't we see this anaphylaxis in other type III hypersensitivity reactions then (ex. post-Streptococcal glomerulonephritis, SLE, etc)? Is it because, after the transfusion, the donor IgA is much more "systemic" (ie. there's lots of it floating around all through the bloodstream) and complement is activated everywhere rather than antigen-antibody complexes depositing in certain tissues and activating complement locally?

 

[thecalccobra]

I'm confused as well. Pholston, just like you, I was under the impression that, when discussing anaphylaxis, we're referring to an IgE-mediated, type I hypersensitivity reaction.

Why would a type III reaction lead to anaphylaxis? I understand that activation of complement will lead to production of the anaphylatoxins, which can induce mast cell degranulation. But why don't we see this anaphylaxis in other type III hypersensitivity reactions then (ex. post-Streptococcal glomerulonephritis, SLE, etc)? Is it because, after the transfusion, the donor IgA is much more "systemic" (ie. there's lots of it floating around all through the bloodstream) and complement is activated everywhere rather than antigen-antibody complexes depositing in certain tissues and activating complement locally?

I have the exact same question :/ Anyone wanna chime in?

 

[Myxedema]

Why do you assume this is a type III hypersensitivity? From Harrison's:

Patients who are IgA-deficient, <1% of the population, may be sensitized to this Ig class and are at risk for anaphylactic reactions associated with plasma transfusion. Individuals with severe IgA deficiency should therefore receive only IgA-deficient plasma and washed cellular blood components. Patients who have anaphylactic or repeated allergic reactions to blood components should be tested for IgA deficiency.

This is no different from a person with peanut allergy being warned to stay away from peanuts. IgA is sensed as a foreign antigen --> When patient become sensitized, IgE production leads to mast cell activation and degranulation, which produces the mediators of anaphlyaxis (whether it is histamine, LTs, C3a/C5a, etc.)

 

[Jamiu22]

Why do you assume this is a type III hypersensitivity? From Harrison's:

This is no different from a person with peanut allergy being warned to stay away from peanuts. IgA is sensed as a foreign antigen --> When patient become sensitized, IgE production leads to mast cell activation and degranulation, which produces the mediators of anaphlyaxis (whether it is histamine, LTs, C3a/C5a, etc.)

 

[IkramKhaliq]

Why do you assume this is a type III hypersensitivity? From Harrison's:

This is no different from a person with peanut allergy being warned to stay away from peanuts. IgA is sensed as a foreign antigen --> When patient become sensitized, IgE production leads to mast cell activation and degranulation, which produces the mediators of anaphlyaxis (whether it is histamine, LTs, C3a/C5a, etc.)

So an IgA deficient person would not develop anaphylaxis the first time they get a transfusion? That does not go with what UW says (what Phloston wrote in the first post on this thread).