Study of microRNAs (miRNAs) that are predicted to target the autoantigens Ro/SSA and La/SSB in primary Sjögren's Syndrome

Abstract

1 These authors contributed equally to the study. SummaryThe elevated tissue expression of Ro/SSA and La/SSB autoantigens appears to be crucial for the generation and perpetuation of autoimmune humoral responses against these autoantigens in Sj€ ogren's syndrome (SS). The mechanisms that govern their expression are not known. miRNAs, the posttranscriptional regulators of gene expression, might be implicated. We have identified previously the miRNAs let7b, miR16, miR181a, miR200b-3p, miR200b-5p, miR223 and miR483-5p that are predicted to target Ro/SSA [Ro52/tripartite motif-containing protein 21 (TRIM21), Ro60/TROVE domain family, member 2 (TROVE2)] and La/SSB mRNAs. To study possible associations with autoantigen mRNA expression and disease features, their expression was investigated in minor salivary gland (MSG) tissues, peripheral blood mononuclear cells (PBMC) and long-term cultured non-neoplastic salivary gland epithelial cells (SGEC) from 29 SS patients (20 of 29 positive for autoantibodies to Ro/SSA and La/SSB) and 24 sicca-complaining controls. The levels of miR16 were up-regulated in MSGs, miR200b-3p in SGECs and miR223 and miR483-5p in PBMCs of SS patients compared to siccacomplaining controls. The MSG levels of let7b, miR16, miR181a, miR223 and miR483-5p were correlated positively with Ro52/TRIM21-mRNA. miR181a and miR200b-3p were correlated negatively with Ro52/TRIM21 and Ro60/ TROVE2 mRNAs in SGECs, respectively, whereas let7b, miR200b-5p and miR223 associated with La/SSB-mRNA. In PBMCs, let7b, miR16, miR181a and miR483-5p were correlated with Ro52/TRIM21, whereas let7b, miR16 and miR181a were also associated with La/SSB-mRNA expression. Significantly lower miR200b-5p levels were expressed in SS patients with mucosa-associated lymphoid tissue (MALT) lymphoma compared to those without. Our findings indicate that miR16, miR200b-3p, miR223 and miR483-5p are deregulated in SS, but the exact role of this deregulation in disease pathogenesis and autoantigen expression needs to be elucidated.

Decreased microRNA-181a and -16 expression levels in the labial salivary glands of Sj�gren syndrome patients

“…The Ro/SSA and La/SSB intracellular ribonucleoproteins are the major targets of autoimmune humoral responses in SS (18). A literature review found that there were ~30 miRNAs, including miR-181a, miR-16, target Ro/SSA (Ro52/E3 ubiquitin-protein ligase TRIM21 or Ro60/60 kDa SS-A/Ro ribonucleoprotein) and La/SSB mRNAs (19).…”

World Workshop on Oral Medicine VII: Biomarkers predicting lymphoma in the salivary glands of patients with Sjögren’s syndrome—A systematic review

“…Significantly lower levels of miR200b‐5p, a miRNA which regulates expression of autoantibodies directed to intracellular autoantigens, La/SSB, were characterized in SS patients with MALT lymphoma compared with those without ( p < 0.05; Gourzi, Kapsogeorgou, Kyriakidis, & Tzioufas, ). Similarly, in the study of Kapsogeorgou, Papageorgiou, Protogerou, Voulgarelis, and Tzioufas (), miR200b‐5p was significantly downregulated in patients with SS who would develop or had NHL, and was able to discriminate this subset ( p < 0.0001) from those without lymphoma or those with non‐SS sialadenitis.…”

“…Significantly lower levels of miR200b-5p, a miRNA which regulates expression of autoantibodies directed to intracellular autoantigens, La/ SSB, were characterized in SS patients with MALT lymphoma compared with those without (p < 0.05; Gourzi, Kapsogeorgou, Kyriakidis, & Tzioufas, 2015). Similarly, in the study of Kapsogeorgou, Papageorgiou, Protogerou, Voulgarelis, and Tzioufas (2018) Barone et al (2008) reported that CXCL12 was principally detected in infiltrated ducts and malignant B cells in the salivary glands of patients with SS.…”

Comparison of MicroRNA Expression in Tears of Normal Subjects and Sjögren Syndrome Patients

“…Some studies reported the overexpression of miR-146a and miR-155 in the PBMC of patients with primary SS. [24][25][26] Gourzi et al 27 identified miRNAs suspected to target Ro/SSA and La/SSB mRNAs in primary SS as follows: let-7b, miR-16, miR-181a, miR-200b-3p, miR-200b-5p, miR-223, and miR-483-5p. The overexpression of miR-16 in minor salivary glands (MSGs), miR-200b-3p in salivary gland epithelial cells (SGECs), and miR-223 collectively with miR-483-5p in PBMCs of SS patients compared to those in the sicca complaining controls has been reported.…”