Circulating MicroRNAs in Graves' Disease in Relation to Clinical Activity.
Understanding the roles of circulating microRNAs (miRNAs) can provide important and novel information regarding disease pathogenesis and a patient's clinical condition. Circulating miRNAs, such as exosomal miRNA, may regulate various bioactivities related to intercellular communication. However, the circulation of miRNAs in Graves' disease (GD) in relation to disease activity has never been elucidated. This study aimed to identify circulating miRNAs in GD in relation to disease activity and whether their exosomes play a role in the pathogenesis of GD.



Circulating miRNAs were measured in serum obtained from seven intractable GD patients, seven GD patients in remission, and seven healthy controls using the miScript miRNA PCR Array. Altered miRNAs selected from array data were validated in 65 subjects. To investigate exosome biology, peripheral blood mononuclear cells (PBMCs) were incubated with exosomes isolated from the subjects' sera. mRNAs were quantified for cytokines using quantitative real-time polymerase chain reaction.



Circulating miR-23b-5p and miR-92a-39 were increased in GD patients in remission compared with intractable GD patients (p < 0.05). On the other hand, let-7g-3p and miR-339-5p were decreased in GD patients in remission compared with intractable GD patients (p < 0.05). Exosomes from intractable GD patients stimulated mRNA expression for IL-1β and TNF-α compared with GD patients in remission or healthy controls.



This study demonstrates that different levels of circulating miRNAs are associated with intractable GD. Moreover, serum exosomes of patients with intractable GD may activate immune cells, which may play an important role in GD pathogenesis.
1 Department of Endocrinology and Metabolism, Fujita Health University School of Medicine , Aichi, Japan .
Izumi
I
Hiratsuka
2 Department of Hygiene, Fujita Health University School of Medicine , Aichi, Japan .
Hiroya
H
Yamada
3 Department of Biochemistry, Fujita Health University School of Medicine , Aichi, Japan .
Eiji
E
Munetsuna
2 Department of Hygiene, Fujita Health University School of Medicine , Aichi, Japan .
Shuji
S
Hashimoto
1 Department of Endocrinology and Metabolism, Fujita Health University School of Medicine , Aichi, Japan .
Mitsuyasu
M
Itoh
D000328:Adult; D013956:Antithyroid Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D002478:Cells, Cultured; D004351:Drug Resistance; D055354:Exosomes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006111:Graves Disease / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008713:Methimazole / Q000627:therapeutic use; D035683:MicroRNAs / Q000097:blood* / Q000378:metabolism; D008875:Middle Aged; D012074:Remission Induction; D012720:Severity of Illness Index
D013956:Antithyroid Agents; D015415:Biomarkers; C552430:MIRN23a microRNA, human; C543820:MIRN339 microRNA, human; C541874:MIRN92 microRNA, human; D035683:MicroRNAs; C487931:mirnlet7 microRNA, human; D008713:Methimazole