Machine learning identifies clusters of longitudinal autoantibody profiles predictive of systemic lupus erythematosus disease outcomes

被引：43

作者：

Choi, May Yee ^{[1
]}

Chen, Irene ^{[2
]}

Clarke, Ann Elaine ^{[1
]}

Fritzler, Marvin J. ^{[1
]}

Buhler, Katherine A. ^{[1
]}

Urowitz, Murray ^{[3
]}

Hanly, John ^{[4
,5
,6
]}

St-Pierre, Yvan ^{[7
]}

Gordon, Caroline ^{[8
]}

Bae, Sang-Cheol ^{[9
,10
]}

Romero-Diaz, Juanita ^{[11
]}

Sanchez-Guerrero, Jorge ^{[12
,13
]}

Bernatsky, Sasha ^{[14
,15
]}

Wallace, Daniel J. ^{[16
]}

Isenberg, David Alan ^{[17
]}

Rahman, Anisur ^{[17
]}

Merrill, Joan T. ^{[18
]}

Fortin, Paul R. ^{[19
]}

Gladman, Dafna D. ^{[3
]}

Bruce, Ian N. ^{[20
]}

Petri, Michelle ^{[21
]}

Ginzler, Ellen M. ^{[22
]}

Dooley, Mary Anne ^{[23
]}

Ramsey-Goldman, Rosalind ^{[24
,25
]}

Manzi, Susan ^{[26
]}

Jonsen, Andreas ^{[27
]}

Alarcon, Graciela S. ^{[28
]}

van Vollenhoven, Ronald F. ^{[29
]}

Aranow, Cynthia ^{[30
]}

Mackay, Meggan ^{[30
]}

Ruiz-Irastorza, Guillermo ^{[31
]}

Lim, Sam ^{[32
]}

Inanc, Murat ^{[33
]}

Kalunian, Kenneth ^{[34
]}

Jacobsen, Soren ^{[35
]}

Peschken, Christine ^{[36
]}

Kamen, Diane L. ^{[37
]}

Askanase, Anca ^{[38
]}

Buyon, Jill P. ^{[39
]}

Sontag, David ^{[2
]}

Costenbader, Karen H. ^{[40
,41
]}

机构：

[1] Univ Calgary, Med, Cumming Sch Med, Calgary, AB, Canada

[2] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA USA

[3] Univ Toronto, Toronto Western Hosp, Ctr Prognosis Studies Rheumat Dis, Lupus Clin, Toronto, ON, Canada

[4] Queen Elizabeth 2 Hlth Sci Ctr, Dept Med, Div Rheumatol, Halifax, NS, Canada

[5] Queen Elizabeth 2 Hlth Sci Ctr, Dept Pathol, Halifax, NS, Canada

[6] Dalhousie Univ, Halifax, NS, Canada

[7] McGill Univ, Med, Res Inst, Hlth Ctr, Montreal, PQ, Canada

[8] Univ Birmingham, Inst Inflammat & Ageing, Coll Med & Dent Sci, Rheumatol Res Grp,Med Sch, Birmingham, England

[9] Hanyang Univ, Hanyang Univ Hosp Rheumat Dis, Inst Rheumatol, Rheumatol, Seoul, South Korea

[10] Hanyang Univ, Inst Biosci & Biotechnol, Seoul, South Korea

[11] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Immunol & Rheumatol, Mexico City, DF, Mexico

[12] Univ Toronto, Mt Sinai Hosp, Toronto, ON, Canada

[13] Univ Toronto, Univ Hlth Network, Toronto, ON, Canada

[14] McGill Univ, Hlth Ctr, Div Rheumatol, Montreal, PQ, Canada

[15] McGill Univ, Hlth Ctr, Div Clin Epidemiol, Montreal, PQ, Canada

[16] UCLA, Div Rheumatol, Cedars Sinai David Geffen Sch Med, Los Angeles, CA USA

[17] UCL, Ctr Rheumatol, Dept Med, London, England

[18] Oklahoma Med Res Fdn, Dept Clin Pharmacol, Oklahoma City, OK USA

[19] Univ Laval, Div Rheumatol, CHU Quebec, Quebec City, PQ, Canada

[20] Univ Manchester, Epidemiol Unit, Manchester, England

[21] Johns Hopkins Univ, Div Rheumatol, Sch Med, Baltimore, MD USA

[22] SUNY Downstate Med Ctr, Dept Med, Brooklyn, NY USA

[23] Univ North Carolina Chapel Hill, Thurston Arthrit Res Ctr, Chapel Hill, NC USA

[24] Northwestern Univ, Dept Med, Div Rheumatol, Chicago, IL USA

[25] Feinberg Sch Med, Chicago, IL USA

[26] Allegheny Hlth Network, Med, Pittsburgh, PA USA

[27] Lund Univ, Clin Sci, Lund, Sweden

[28] Univ Alabama Birmingham, Dept Med, Heersink Sch Med, Birmingham, AL USA

[29] Univ Amsterdam, Rheumatol & Immunol Ctr, Amsterdam, Netherlands

[30] Feinstein Inst Med Res, Div Autoimmune & Musculoskeletal Dis, Manhasset, NY USA

[31] Univ Basque Country, Hosp Univ Cruces, BioCruces Hlth Res Inst, Dept Internal Med,Autoimmune Dis Res Unit, Baracaldo, Spain

[32] Emory Univ, Div Rheumatol, Sch Med, Atlanta, GA USA

[33] Istanbul Univ, Istanbul Med Fac, Dept Internal Med, Div Rheumatol, Istanbul, Turkiye

[34] Univ Calif San Diego, Dept Rheumatol Allergy & Immunol, La Jolla, CA USA

[35] Copenhagen Univ Hosp, Dept Rheumatol, Rigshosp, Copenhagen, Denmark

[36] Univ Manitoba, Internal Med, Winnipeg, MB, Canada

[37] Med Univ South Carolina, Div Rheumatol & Immunol, Charleston, SC USA

[38] NYU, Hosp Joint Dis, Seligman Ctr Adv Therapeut, New York, NY USA

[39] NYU, Div Rheumatol, Sch Med, New York, NY USA

[40] Brigham & Womens Hosp, Dept Med, Div Rheumatol Inflammat & Immun, Boston, MA USA

[41] Harvard Med Sch, Med, Boston, MA USA

来源：

ANNALS OF THE RHEUMATIC DISEASES | 2023年 / 82卷 / 07期

基金：

新加坡国家研究基金会; 加拿大健康研究院; 英国惠康基金;

关键词：

systemic lupus erythematosus; autoantibodies; autoimmunity; ANTIPHOSPHOLIPID ANTIBODIES; NEUROPSYCHIATRIC EVENTS; ANTINUCLEAR ANTIBODIES; INDEX; CLASSIFICATION; SEROCONVERSION; CRITERIA; SUBSETS; DAMAGE; TIME;

D O I：

10.1136/ard-2022-223808

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

ObjectivesA novel longitudinal clustering technique was applied to comprehensive autoantibody data from a large, well-characterised, multinational inception systemic lupus erythematosus (SLE) cohort to determine profiles predictive of clinical outcomes. MethodsDemographic, clinical and serological data from 805 patients with SLE obtained within 15 months of diagnosis and at 3-year and 5-year follow-up were included. For each visit, sera were assessed for 29 antinuclear antibodies (ANA) immunofluorescence patterns and 20 autoantibodies. K-means clustering on principal component analysis-transformed longitudinal autoantibody profiles identified discrete phenotypic clusters. One-way analysis of variance compared cluster enrolment demographics and clinical outcomes at 10-year follow-up. Cox proportional hazards model estimated the HR for survival adjusting for age of disease onset. ResultsCluster 1 (n=137, high frequency of anti-Smith, anti-U1RNP, AC-5 (large nuclear speckled pattern) and high ANA titres) had the highest cumulative disease activity and immunosuppressants/biologics use at year 10. Cluster 2 (n=376, low anti-double stranded DNA (dsDNA) and ANA titres) had the lowest disease activity, frequency of lupus nephritis and immunosuppressants/biologics use. Cluster 3 (n=80, highest frequency of all five antiphospholipid antibodies) had the highest frequency of seizures and hypocomplementaemia. Cluster 4 (n=212) also had high disease activity and was characterised by multiple autoantibody reactivity including to antihistone, anti-dsDNA, antiribosomal P, anti-Sjogren syndrome antigen A or Ro60, anti-Sjogren syndrome antigen B or La, anti-Ro52/Tripartite Motif Protein 21, antiproliferating cell nuclear antigen and anticentromere B). Clusters 1 (adjusted HR 2.60 (95% CI 1.12 to 6.05), p=0.03) and 3 (adjusted HR 2.87 (95% CI 1.22 to 6.74), p=0.02) had lower survival compared with cluster 2. ConclusionFour discrete SLE patient longitudinal autoantibody clusters were predictive of long-term disease activity, organ involvement, treatment requirements and mortality risk.

引用

页码：927 / 936

页数：10

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