Activation of complement by human serum IgA, secretory IgA and IgA1 fragments.
Activation of the complement (C) system by human IgA was studied. Both subclasses of IgA, IgA1 and IgA2, and secretory IgA were shown to activate C, as determined by deposition of C3 on glutaraldehyde-activated microwells coated with IgA. The activation of the C system occurred in the presence of MgEGTA and not in D-deficient serum. In addition to C3, deposition of properdin (P) but not of C4 was detected. These results indicate that C activation, as determined by measuring deposition of C3 and P, occurred by the alternative pathway (AP). The data further show that the major part of the hinge region, which is deleted in IgA2 as compared with IgA1 and which forms the major structural difference between the two subclasses, is not involved in C activation. Reduction and alkylation destroyed the ability of IgA to activate C, as has also been demonstrated for IgG. In order to define the C activating region of the IgA molecule, several fragments of IgA1 were tested. The four-chain molecules F(ab')2 and F(abc)2 were shown to activate the AP. No activation was observed with the two-chain fragments Fab and Fc. The Fc fragment of IgA also did not activate the CP, as does the Fc fragment of IgG. This indicates that activation of the AP of C by IgA is dependent on the presence of the F(ab')2 fragment.


CONCLUSIONS
human IgA does activate C by the AP. This activation requires an intact F(ab')2 fragment.
Hiemstra
P S
PS
Department of Nephrology, University Hospital, Leiden, The Netherlands.
Biewenga
J
J
Gorter
A
A
Stuurman
M E
ME
Faber
A
A
van Es
L A
LA
Daha
M R
MR
D003167:Complement Activation; D003170:Complement Pathway, Alternative; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007070:Immunoglobulin A / Q000145:classification / Q000276:immunology*; D007071:Immunoglobulin A, Secretory / Q000276:immunology; D007140:Immunoglobulin Fab Fragments / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology; D009194:Myeloma Proteins / Q000276:immunology
D007070:Immunoglobulin A; D007071:Immunoglobulin A, Secretory; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D009194:Myeloma Proteins