Unique Sjogren's syndrome patient subsets defined by molecular features

被引：46

作者：

James, Judith A. ^{[1
,2
,3
]}

Guthridge, Joel M. ^{[1
,2
]}

Chen, Hua ^{[1
]}

Lu, Rufei ^{[1
,2
]}

Bourn, Rebecka L. ^{[1
]}

Bean, Krista ^{[1
]}

Munroe, Melissa E. ^{[1
]}

Smith, Miles ^{[1
]}

Chakravarty, Eliza ^{[1
]}

Baer, Alan N. ^{[4
]}

Noaiseh, Ghaith ^{[5
]}

Parke, Ann ^{[6
]}

Boyle, Karen ^{[7
]}

Keyes-Elstein, Lynette ^{[7
]}

Coca, Andreea ^{[8
]}

Utset, Tammy ^{[9
]}

Genovese, Mark C. ^{[10
]}

Pascual, Virginia ^{[11
]}

Utz, Paul J. ^{[10
]}

Holers, V. Michael ^{[12
]}

Deane, Kevin D. ^{[12
]}

Sivils, Kathy L. ^{[1
]}

Aberle, Teresa ^{[1
]}

Wallace, Daniel J. ^{[13
]}

McNamara, James ^{[14
]}

Franchimont, Nathalie ^{[15
]}

St Clair, E. William ^{[16
]}

机构：

[1] Oklahoma Med Res Fdn, Arthrit & Clin Immunol, 825 NE 13th St, Oklahoma City, OK 73104 USA

[2] Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK USA

[3] Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK USA

[4] Johns Hopkins Univ, Sch Med, Dept Med, Div Rheumatol, Baltimore, MD 21205 USA

[5] Univ Pittsburgh, Dept Med, Div Rheumatol & Clin Immunol, Med Ctr, Pittsburgh, PA USA

[6] Univ Connecticut, Div Rheumat Dis, Farmington, CT USA

[7] Rho Fed Syst Div, Chapel Hill, NC USA

[8] Univ Rochester, Med Ctr, Dept Med, Rochester, NY 14642 USA

[9] Univ Chicago, Dept Med, 5841 S Maryland Ave, Chicago, IL 60637 USA

[10] Stanford Univ, Immunol & Rheumatol, Sch Med, Stanford, CA USA

[11] Weill Cornell Med, Drukier Inst Childrens Hlth, New York, NY USA

[12] Univ Colorado, Div Rheumatol, Sch Med, Aurora, CO USA

[13] Cedars Sinai Med Ctr, Dept Med, West Hollywood, CA USA

[14] NIAID, Div Allergy Immunol & Transplantat, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA

[15] Biogen, Cambridge, MA USA

[16] Duke Univ, Sch Med, Dept Med, Div Rheumatol & Immunol, Durham, NC 27706 USA

来源：

RHEUMATOLOGY | 2020年 / 59卷 / 04期

基金：

美国国家卫生研究院;

关键词：

Sjogren's syndrome; precision medicine; biomarkers; interferon; SYSTEMIC-LUPUS-ERYTHEMATOSUS; INTERFERON TYPE-I; T-CELLS; DISEASE-ACTIVITY; EXPRESSION; CD40; SIGNATURES; CYTOKINE; RECEPTOR; LIGHT;

D O I：

10.1093/rheumatology/kez335

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Objective. To address heterogeneity complicating primary SS (pSS) clinical trials, research and care by characterizing and clustering patients by their molecular phenotypes. Methods. pSS patients met American-European Consensus Group classification criteria and had at least one systemic manifestation and stimulated salivary flow of 0.1 ml/min. Correlated transcriptional modules were derived from gene expression microarray data from blood (n = 47 with appropriate samples). Patients were clustered based on this molecular information using an unbiased random forest modelling approach. In addition, multiplex, bead-based assays and ELISAs were used to assess 30 serum cytokines, chemokines and soluble receptors. Eleven autoantibodies, including anti-Ro/SSA and anti-La/SSB, were measured by Bio-Rad Bioplex 2200. Results. Transcriptional modules distinguished three clusters of pSS patients. Cluster 1 showed no significant elevation of IFN or inflammation modules. Cluster 2 showed strong IFN and inflammation modular network signatures, as well as high plasma protein levels of IP-10/CXCL10, MIG/CXCL9, BLyS (BAFF) and LIGHT. Cluster 3 samples exhibited moderately elevated IFN modules, but with suppressed inflammatory modules, increased IP-10/CXCL10 and B cell-attracting chemokine 1/CXCL13 and trends toward increased MIG/CXCL9, IL-1 alpha, and IL-21. Anti-Ro/SSA and anti-La/SSB were present in all three clusters. Conclusion. Molecular profiles encompassing IFN, inflammation and other signatures can be used to separate patients with pSS into distinct clusters. In the future, such profiles may inform patient selection for clinical trials and guide treatment decisions.

引用

页码：860 / 868

页数：9

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