4
$\begingroup$

Recently, I have been reading Janeway's immunobiology and had a question on immunoglobin A. I read that IgA activates the complement pathway using the Fab fragment of the IgA. How does IgA do that? I can't seem to find an information on that in the book or online.

$\endgroup$
  • $\begingroup$ @anongoodnurse 4th edition.. in Fig 3.20 on pg 102, it mentions that alternative complement pathway activated by Fab for IgA1 $\endgroup$ – TanMath Jan 1 '15 at 7:33
  • $\begingroup$ In the 2011 edition, compliment activation is discussed beginning in Ch. 10. $\endgroup$ – anongoodnurse Jan 2 '15 at 4:01
  • $\begingroup$ Oh, the 4th editions is very old. Even the NIH bookshelf has the 5th edition. Can you link the figure from the NIH edition so we know which one you are talking about? $\endgroup$ – Chris Jan 2 '15 at 12:01
  • $\begingroup$ @Chris in the 5th edition, the figure is 4.16 $\endgroup$ – TanMath Jan 2 '15 at 19:39
6
$\begingroup$

I found some reports on it (like reference 1) but there is an oddly little amount of publications on this topic. then I found this review in Mucosal Immunology (reference 2, interesting to read) which doubts this activation. It says:

Interaction with complement

IgA lacks the residues identified in the Fc regions of IgG or IgM that bind to C1q, and consequently IgA does not activate the classical complement pathway. Although several papers have reported activation of the alternate pathway by heat-aggregated, denatured, or recombinantly generated IgA, this seems to be essentially artifactual, and intact native IgA antibodies complexed with antigen inhibit complement activation induced by IgG or IgM antibodies. This effect is also replicated by Fabα fragments generated by cleavage of IgA1 antibodies with IgA1 protease. It is telling that mixed aggregates of heat-denatured IgG and IgA activate the alternate pathway in proportion to the content of IgG, and that C3b becomes covalently linked to the IgG heavy chains, not to IgA. Intriguing reports that IgA antibodies promote complement-dependent lysis or opsonization of encapsulated bacteria probably also arise from facilitation of alternate pathway activation by bacterial polysaccharides

It names three papers to underline this (which are number 45-47 in the reference list of the article), which can be found as references 3-5. So the question here is not only how the mechanism looks like, but also if this is real or an artefact.

References:

  1. Activation of complement by human serum IgA, secretory IgA and IgA1 fragments.
  2. Structure and function relationships in IgA
  3. Anti-inflammatory activity of human IgA antibodies and their Fabα fragments: inhibition of IgG-mediated complement activation
  4. IgA blocks IgM and IgG-initiated immune lysis by separate molecular mechanisms.
  5. Activity of human IgG and IgA subclasses in immune defense against Neisseria meningitidis serogroup B.
$\endgroup$
  • 1
    $\begingroup$ Janeway says much the same thing in different words. IgA is a very minor player in compliment activation, and even then, only in certain situations. $\endgroup$ – anongoodnurse Jan 3 '15 at 11:17
0
$\begingroup$

Roos et al (Journal of Immunology, 2001, reference below) suggests that IgA binds MBL, and activates complement by facilitating the lectin binding pathway for complement activation rather than being a major player in the alternate pathway.

Another group of researchers (Daha et al, in Nephrology Dialysis Transplantation, 2006) discusses a potential fourth method for complement activation, as well as describing IgA nephropathy as a result of both alternate- and lectin-activated complement activity. (second reference)

http://www.jimmunol.org/content/167/5/2861.full

http://ndt.oxfordjournals.org/content/21/12/3374.full.pdf

$\endgroup$
  • $\begingroup$ Your third paragraph is slightly confusing. "Has this been discredited?" and then you provide two sources. Are you asking if those articles have been discredited, in which case that should not be part of an answer but should be raised as your own question? Please try to rephrase to make the intention of your answer clear. Thank you. $\endgroup$ – AMR Nov 23 '15 at 2:36
  • $\begingroup$ I think you're right, AML--I decided just to remove the third paragraph entirely, and let the research articles I quoted speak for themselves. $\endgroup$ – microbe29 Nov 23 '15 at 16:28

Your Answer

By clicking “Post Your Answer”, you agree to our terms of service, privacy policy and cookie policy

Not the answer you're looking for? Browse other questions tagged or ask your own question.