Atypical autoantigen targets of perinuclear antineutrophil cytoplasm antibodies (P-ANCA): specificity and clinical associations.
Atypical antineutrophil cytoplasm antibodies (A-ANCA) are defined here as ANCA detected by IIF and not directed against the predominant ANCA antigens, proteinase 3 (PR3) and myeloperoxidase (MPO). A-ANCA are found in a variety of clinical conditions, namely rheumatoid arthritis, inflammatory bowel diseases, chronic hepatic diseases and several infections including HIV infection. They are directed against a variety of still ill-defined neutrophil antigens and most frequently yield a perinuclear pattern (P-ANCA) of binding by indirect immunofluorescence on ethanol fixed neutrophils. This paper reviews the literature on A-ANCA and our recent data suggesting that, among others, cathepsin G is one of the predominant antigen targets of A-ANCA. From a clinical point of view, the distinction between MPO-ANCA and A-ANCA is not possible by indirect immunofluorescence (IIF). The determination of ANCA antigens by specific ELISA is therefore necessary to differentiate P-ANCA with MPO specificity from those with undefined specificity. This is of importance because the clinical value of MPO-ANCA is clearly established while the presence of A-ANCA is difficult to interpret given their occurrence in a large variety of clinical conditions.
Department of Nephrology, Hôpital Necker, Paris, France.
P
P
Lesavre
L H
LH
Noël
S
S
Gayno
P
P
Nusbaum
D
D
Reumaux
S
S
Erlinger
J P
JP
Grünfeld
L
L
Halbwachs-Mecarelli
D019268:Antibodies, Antineutrophil Cytoplasmic; D000918:Antibody Specificity; D001172:Arthritis, Rheumatoid / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology*; D056649:Cathepsin G; D002403:Cathepsins / Q000276:immunology; D003593:Cytoplasm / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D006801:Humans; D007239:Infections / Q000276:immunology; D015212:Inflammatory Bowel Diseases / Q000276:immunology; D008107:Liver Diseases / Q000276:immunology; D053146:Myeloblastin; D009504:Neutrophils / Q000276:immunology* / Q000648:ultrastructure; D010196:Pancreatic Elastase / Q000276:immunology; D009195:Peroxidase / Q000276:immunology; D012697:Serine Endopeptidases / Q000276:immunology
D019268:Antibodies, Antineutrophil Cytoplasmic; D001323:Autoantibodies; D001324:Autoantigens; D009195:Peroxidase; D002403:Cathepsins; D012697:Serine Endopeptidases; C534094:CTSG protein, human; D056649:Cathepsin G; D010196:Pancreatic Elastase; D053146:Myeloblastin