Identification of Three Rheumatoid Arthritis Disease Subtypes by Machine Learning Integration of Synovial Histologic Features and RNA Sequencing Data.

Autor: Orange DE; Hospital for Special Surgery, The Rockefeller University, and New York Genome Center, New York, New York., Agius P; New York Genome Center, New York, New York., DiCarlo EF; Hospital for Special Surgery, New York, New York., Robine N; New York Genome Center, New York, New York., Geiger H; New York Genome Center, New York, New York., Szymonifka J; Hospital for Special Surgery, New York, New York., McNamara M; Hospital for Special Surgery, New York, New York., Cummings R; Hospital for Special Surgery, New York, New York., Andersen KM; Hospital for Special Surgery, New York, New York., Mirza S; Hospital for Special Surgery, New York, New York., Figgie M; Hospital for Special Surgery, New York, New York., Ivashkiv LB; Hospital for Special Surgery, New York, New York., Pernis AB; Hospital for Special Surgery, New York, New York., Jiang CS; The Rockefeller University Hospital, New York, New York., Frank MO; The Rockefeller University and New York Genome Center, New York, New York., Darnell RB; The Rockefeller University and New York Genome Center, New York, New York., Lingampali N; Stanford University School of Medicine, Stanford, California., Robinson WH; Stanford University School of Medicine, Stanford, California., Gravallese E; University of Massachusetts Memorial Medical Center, Worcester., Bykerk VP; Hospital for Special Surgery, New York, New York., Goodman SM; Hospital for Special Surgery, New York, New York., Donlin LT; Hospital for Special Surgery, New York, New York.
Jazyk: angličtina
Zdroj: Arthritis & rheumatology (Hoboken, N.J.) [Arthritis Rheumatol] 2018 May; Vol. 70 (5), pp. 690-701. Date of Electronic Publication: 2018 Apr 02.
DOI: 10.1002/art.40428
Abstrakt: Objective: In this study, we sought to refine histologic scoring of rheumatoid arthritis (RA) synovial tissue by training with gene expression data and machine learning.
Methods: Twenty histologic features were assessed in 129 synovial tissue samples (n = 123 RA patients and n = 6 osteoarthritis [OA] patients). Consensus clustering was performed on gene expression data from a subset of 45 synovial samples. Support vector machine learning was used to predict gene expression subtypes, using histologic data as the input. Corresponding clinical data were compared across subtypes.
Results: Consensus clustering of gene expression data revealed 3 distinct synovial subtypes, including a high inflammatory subtype characterized by extensive infiltration of leukocytes, a low inflammatory subtype characterized by enrichment in pathways including transforming growth factor β, glycoproteins, and neuronal genes, and a mixed subtype. Machine learning applied to histologic features, with gene expression subtypes serving as labels, generated an algorithm for the scoring of histologic features. Patients with the high inflammatory synovial subtype exhibited higher levels of markers of systemic inflammation and autoantibodies. C-reactive protein (CRP) levels were significantly correlated with the severity of pain in the high inflammatory subgroup but not in the others.
Conclusion: Gene expression analysis of RA and OA synovial tissue revealed 3 distinct synovial subtypes. These labels were used to generate a histologic scoring algorithm in which the histologic scores were found to be associated with parameters of systemic inflammation, including the erythrocyte sedimentation rate, CRP level, and autoantibody levels. Comparison of gene expression patterns to clinical features revealed a potentially clinically important distinction: mechanisms of pain may differ in patients with different synovial subtypes.
(© 2018, American College of Rheumatology.)
Databáze: MEDLINE
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