Saturday, February 7, 2015

antigen-specific IgG1 isotype protects against type III allergy (hypersensitivity)

IgG antibody family consists of four isotypes: IgG1, IgG2a, IgG2b and IgG3 (IgG1-4, in humans). They differ in their Fc portions. Current knowledge suggests that IgG isotypes have different function depending on a degree of their interactions with complement and FcRs.  

New study in journal Nature, however, provided evidence for complement- and FcR-independent function of IgG1 isotype.

This research led by Fred Finkelman at the University of Cincinnati College of Medicine, have analysed immune response of mice deficient for IgG1 isotype (Igγ1mice). Strangely, immunization with goat anti-mouse IgD anti-serum (GaMD, protein immunogen) led to the death of Igγ1- mice, but not wild-type mice.

The authors showed that this death of Igγ1mice was caused by kidney insufficiency.

Analysis of immune response to GaMD in Igγ1mice revealed selective increase in antigen-specific IgG3 isotype and IgM in serum and their deposition in kidney's glomerular capillaries. Interestingly, kidney damage in Igγ1mice was still present in FcγR1- or FcγR1- and complement C3 double deficient mice.

The authors showed that kidney damage could occur even in wild-type mice by passive injection of antigen (TNP)-specific IgG3 and antigen (TNP-protein). Other IgG isotypes did not induce renal disease.

Importantly, concomitant injection of antigen specific IgG1 and disease-inducing IgG3 could prevent renal disease development independent of complement C3 or inhibitory FcγRIIb.

In summary, these results indicate that induction of antigen-specific IgG1 response during protein immunization prevents the development of type III hypersensitivity. Mechanistically, IgG1 competes for antigen binding with antigen-specific IgG3, thus inhibiting large antigen-antibody complex formations typical for IgG3.

This new knowledge could help to design new treatments for human cryoglobulinemia.

David Usharauli

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