title: IgA- and SIgA anti-PR3 antibodies in serum versus organ involvement and disease activity in PR3-ANCA-associated vasculitis.
abstract: Circulating immunoglobulin (Ig)A class anti-neutrophil cytoplasm antibodies (ANCA) directed against proteinase 3 (PR3) have been reported in ANCA-associated vasculitis (AAV) with mucosal involvement. However, secretory IgA (SIgA) PR3-ANCA has not been reported previously. In this study we compared serum levels of SIgA PR3-ANCA and IgA PR3-ANCA with IgG PR3-ANCA in relation to disease characteristics. Among 73 patients with AAV and PR3-ANCA at diagnosis, 84% tested positive for IgG PR3-ANCA, 47% for IgA-ANCA and 36% for SIgA PR3-ANCA at the time of sampling for the present study. IgA and IgG PR3-ANCA were represented similarly among patients with different organ manifestations, i.e. upper airway, lung or kidney at time of sampling. However, SIgA PR3-ANCA was significantly less represented among patients with upper airway involvement. During active disease, the proportions of IgA PR3-ANCA and SIgA PR3-ANCA-positive patients were significantly higher compared to inactive disease. Eight patients were sampled prospectively during 24 months from onset of active disease. In these patients, IgA PR3-ANCA and SIgA PR3-ANCA turned negative more often after remission induction compared to IgG PR3-ANCA. Our findings suggest that serum IgA PR3-ANCA and SIgA PR3-ANCA are related more closely to disease activity in AAV compared to IgG PR3-ANCA. Further studies are required to reveal if this has implications for disease activity monitoring. The mean number of PR3-ANCA isotypes increased along with disease activity, suggesting a global B cell activation during active disease.
authors.affiliation: Department of Rheumatology and Department of Clinical and Experimental Medicine.
authors.forename: C
authors.initials: C
authors.lastname: Sandin
authors.affiliation: Department of Rheumatology and Department of Clinical and Experimental Medicine.
authors.forename: P
authors.initials: P
authors.lastname: Eriksson
authors.affiliation: Division of Nephrology and Division of Drug Research, Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Segelmark
authors.affiliation: Department of Rheumatology and Department of Clinical and Experimental Medicine.
authors.forename: T
authors.initials: T
authors.lastname: Skogh
authors.affiliation: Department of Rheumatology and Department of Clinical and Experimental Medicine.
authors.forename: A
authors.initials: A
authors.lastname: Kastbom
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000097:blood* / Q000276:immunology; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000097:blood* / Q000276:immunology; D005260:Female; D006801:Humans; D007071:Immunoglobulin A, Secretory / Q000097:blood* / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood* / Q000276:immunology; D007668:Kidney / Q000473:pathology; D008168:Lung / Q000473:pathology; D008297:Male; D008875:Middle Aged; D053146:Myeloblastin / Q000276:immunology*; D055815:Young Adult
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D007071:Immunoglobulin A, Secretory; D007074:Immunoglobulin G; D053146:Myeloblastin
keywords: ANCA-associated vasculitis; IgA PR3-ANCA; disease; mucosal immunity activity