Circulating Cytokine Profiles and Antineutrophil Cytoplasmic Antibody Specificity in Patients With Antineutrophil Cytoplasmic Antibody-Associated Vasculitis

被引:56
作者
Berti, Alvise [1 ,2 ,3 ]
Warner, Roscoe [4 ]
Johnson, Kent [4 ]
Cornec, Divi [1 ,5 ]
Schroeder, Darrell [1 ]
Kabat, Brian [1 ]
Langford, Carol A. [6 ]
Hoffman, Gary S. [6 ]
Fervenza, Fernanado C. [1 ]
Kallenberg, Cees G. M. [7 ]
Seo, Philip [8 ]
Spiera, Robert [9 ]
St Clair, E. William [10 ]
Brunetta, Paul [11 ]
Stone, John H. [12 ]
Merkel, Peter A. [13 ]
Specks, Ulrich [1 ]
Monach, Paul A. [14 ,15 ]
机构
[1] Mayo Clin, Coll Med & Sci, Rochester, MN 55905 USA
[2] San Raffaele Univ, Milan, Italy
[3] Santa Chiara Hosp, Trento, Italy
[4] Univ Michigan, Sch Med, Ann Arbor, MI USA
[5] Univ Bretagne Occidentale, CHU Brest, Brest, France
[6] Cleveland Clin, Cleveland, OH 44106 USA
[7] Univ Med Ctr Groningen, Groningen, Netherlands
[8] Johns Hopkins Univ, Baltimore, MD USA
[9] Hosp Special Surg, 535 E 70th St, New York, NY 10021 USA
[10] Duke Univ, Med Ctr, Durham, NC USA
[11] Genentech Inc, San Francisco, CA 94080 USA
[12] Massachusetts Gen Hosp, Boston, MA 02114 USA
[13] Univ Penn, Philadelphia, PA 19104 USA
[14] Boston Univ, Boston, MA 02215 USA
[15] VA Boston Healthcare Syst, Boston, MA USA
关键词
ANCA-ASSOCIATED VASCULITIS; CLINICAL UTILITY; INJURY;
D O I
10.1002/art.40471
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 [PR3-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, CXCL8/IL-8, CCL-17/thymus and activation-regulated chemokine [TARC], IL-18 binding protein [IL-18 BP], soluble IL-2 receptor [sIL-2R], and nerve growth factor [NGF]) were significantly higher in PR3-AAV than MPO-AAV, 4 cytokines (sIL6R, 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 PR3-AAV, 6 cytokines (IL-6, GM-CSF, IL-15, IL-18, sIL-2R, and NGF) 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 PR3-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-, sICAM-1, TARC, osteopontin, andkidney 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 PR3-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.
引用
收藏
页码:1114 / 1121
页数:8
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