Predominance of IgG1 and IgG4 subclasses of anti-neutrophil cytoplasmic autoantibodies (ANCA) in patients with Wegener's granulomatosis and clinically related disorders.
In view of the supposed hypersensitivity, the elevated levels of IgE, and the occurrence of eosinophilia reported in Wegener's granulomatosis and related conditions, we studied the IgG subclass distribution of ANCA directed against a 29-kD serine protease and myeloperoxidase (MPO) in 41 untreated ANCA-positive patients with several forms of active vasculitis and/or glomerulonephritis. We found that both 29-kD ANCA and MPO ANCA were predominantly of the IgG1 and IgG4 subclass in all groups of patients. The additional presence of IgG3 subclass was associated with renal involvement. We compared the subclass distribution of ANCA with that of total IgG subclass levels, and with the IgG subclass distribution of antibodies to cytomegalovirus (CMV) as a persistent endogenous antigen and antibodies to tetanus toxoid (TT) as an exogenous recall antigen. Total levels of IgG4 were elevated in the majority of the patients together with elevated IgG1 levels. Antibodies to CMV and TT, however, had the same subclass distribution as found in normals and did not show enhanced IgG4 expression. ANCA belong predominantly to the IgG1 and IgG4 subclass, which may suggest that the production of ANCA is related to recurrent exposition to the antigen(s) involved, possibly as part of a hypersensitivity reaction.
Brouwer
E
E
Department of Clinical Immunology, University Hospital, Groningen, The Netherlands.
Tervaert
J W
JW
Horst
G
G
Huitema
M G
MG
van der Giessen
M
M
Limburg
P C
PC
Kallenberg
C G
CG
D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000032:analysis*; D003587:Cytomegalovirus / Q000276:immunology; D005260:Female; D005921:Glomerulonephritis / Q000276:immunology; D014890:Granulomatosis with Polyangiitis / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007073:Immunoglobulin E / Q000032:analysis; D007074:Immunoglobulin G / Q000032:analysis* / Q000145:classification; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D009504:Neutrophils / Q000201:enzymology / Q000276:immunology*; D009195:Peroxidase / Q000276:immunology; D012697:Serine Endopeptidases / Q000276:immunology; D013745:Tetanus Toxoid / Q000276:immunology; D014657:Vasculitis / Q000276:immunology
D001323:Autoantibodies; D007074:Immunoglobulin G; D013745:Tetanus Toxoid; D007073:Immunoglobulin E; D009195:Peroxidase; D012697:Serine Endopeptidases