Open AccessThe Endogenous Plasma Small RNAome of Rheumatoid Arthritis
Author(s) -
Ormseth Michelle J.,
Solus Joseph F.,
Sheng Quanhu,
Ye Fei,
Song Haocan,
Wu Qiong,
Guo Yan,
Oeser Annette M.,
Allen Ryan M.,
Vickers Kasey C.,
Stein C. Michael
Publication year - 2020
Publication title -
acr open rheumatology
Language(s) - English
Resource type - Journals
ISSN - 2578-5745
DOI - 10.1002/acr2.11098
Subject(s) - small rna , transfer rna , microrna , competing endogenous rna , rheumatoid arthritis , endogeny , biology , rna , gene , disease , case control study , biomarker , medicine , genetics , bioinformatics , immunology , endocrinology , long non coding rna
Objective Small RNA ( sRNA ) sequencing has revealed new sRNA classes beyond micro RNA s (mi RNA s). These sRNA s can regulate genes and act as biomarkers. The aim of this study was to determine if the endogenous plasma sRNA landscape is altered in patients with rheumatoid arthritis ( RA ) compared with control subjects and to determine its association with disease‐related parameters in RA. Methods sRNA sequencing was performed on plasma from 165 RA and 90 control subjects who were frequency‐matched for age, race, and sex. Endogenous sRNA s, such as mi RNA s, isomiRs, sRNA s derived from small nuclear RNA s (sn DR s), small nucleolar RNA s (sno DR s), Y RNA s ( yDR s), transfer‐derived RNA s ( tDR s), long noncoding RNA s (lnc DR s) as well as miscellaneous sRNA s (misc RNA s), were quantified using Tools for Integrative Genome analysis of Extracellular sRNA s ( TIGER ). Individual and categories of sRNA s were compared between RA and controls, and significantly altered sRNA s and sRNA categories were correlated with disease activity and general laboratory measures in RA. Results Patients with RA had more mi RNA s (1.42‐fold, P = 0.01), more tDR s (1.14‐fold, P = 0.04), and fewer yDR s (−1.41‐fold, P = 0.009) compared with control subjects. Disease duration was inversely associated with yDR s. Disease‐related parameters, such as Disease Activity Score‐28 ( DAS 28), swollen joint count, and inflammatory markers were significantly positively associated with tDR s and misc RNA s, and miR‐22‐3p and related sequences and isomiRs were most significantly associated with DAS28. Conclusion Endogenous plasma sRNA s are altered in RA compared with control subjects. Although individual mi RNA s have been well studied and many are excellent biomarkers in RA , several non‐mi RNA sRNA s were significantly associated with disease‐related parameters as classes and may represent novel biomarkers for RA.