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Brief Report: Circulating Cytokine Profiles and Antineutrophil Cytoplasmic Antibody Specificity in Patients With Antineutrophil Cytoplasmic Antibody–Associated Vasculitis
Author(s) -
Berti Alvise,
Warner Roscoe,
Johnson Kent,
Cornec Divi,
Schroeder Darrell,
Kabat Brian,
Langford Carol A.,
Hoffman Gary S.,
Fervenza Fernanado C.,
Kallenberg Cees G. M.,
Seo Philip,
Spiera Robert,
St.Clair E. William,
Brunetta Paul,
Stone John H.,
Merkel Peter A.,
Specks Ulrich,
Monach Paul A.
Publication year - 2018
Publication title -
arthritis and rheumatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.106
H-Index - 314
eISSN - 2326-5205
pISSN - 2326-5191
DOI - 10.1002/art.40471
Subject(s) - microscopic polyangiitis , anti neutrophil cytoplasmic antibody , proteinase 3 , medicine , granulomatosis with polyangiitis , immunology , myeloperoxidase , cytokine , vasculitis , proinflammatory cytokine , osteopontin , inflammation , disease
Objective To evaluate circulating cytokine profiles in patients with antineutrophil cytoplasmic antibody–associated vasculitis ( AAV ), classified by antineutrophil cytoplasmic antibody ( ANCA ) specificity (proteinase 3 ANCA [ PR 3‐ ANCA ] versus myeloperoxidase ANCA [ MPO ‐ ANCA ]) or by clinical diagnosis (granulomatosis with polyangiitis [ GPA ] versus microscopic polyangiitis [ MPA ]). Methods A panel of 29 cytokines was tested in 186 patients with active AAV at inclusion into the Rituximab in AAV trial. Cytokine concentrations were compared between groups within each classification system. Multivariable analyses adjusted for age, sex, and renal insufficiency were performed, with each biomarker as a dependent variable and ANCA specificity and clinical diagnosis as explanatory variables of interest. Results Levels of 9 circulating cytokines (interleukin‐6 [ IL ‐6], granulocyte–macrophage colony‐stimulating factor [ GM ‐ CSF ], IL ‐15, IL ‐18, CXCL 8/ IL ‐8, CCL ‐17/thymus and activation–regulated chemokine [ TARC ], IL ‐18 binding protein [ IL ‐18 BP ], soluble IL ‐2 receptor α [ sIL ‐2Rα], and nerve growth factor β [ NGF β]) were significantly higher in PR 3‐ AAV than MPO ‐ AAV , 4 cytokines ( sIL 6R, soluble tumor necrosis factor receptor type II [ sTNFRII ], neutrophil gelatinase–associated lipocalin [ NGAL ], and soluble intercellular adhesion molecule 1 [ sICAM ‐1]) were higher in MPO ‐ AAV than in PR 3‐ AAV , 6 cytokines ( IL ‐6, GM ‐ CSF , IL ‐15, IL ‐18, sIL ‐2Rα, and NGF β) were higher in GPA than in MPA , and 3 cytokines (osteopontin, sTNFRII , and NGAL ) were higher in MPA than in GPA (all P < 0.05). For nearly all cytokines, the difference between PR 3‐ AAV and MPO ‐ AAV was larger than that between GPA and MPA . The multivariate analysis showed that 8 cytokines ( IL ‐15, IL ‐8, IL ‐18 BP , NGF ‐β, sICAM ‐1, TARC , osteopontin, and kidney injury molecule 1 ( P < 0.05) distinguished patients with AAV better (lower P values and larger effect sizes) when grouped by ANCA specificity than by clinical diagnosis. Conclusion Distinct cytokine profiles were identified for PR 3‐ AAV versus MPO ‐ AAV and for GPA versus MPA . Differences in these circulating immune mediators are more strongly associated with ANCA specificity than with clinical diagnosis, suggesting that heterogeneity in the AAV subtypes extends beyond clinical phenotypes.