Session Information
Title: Systemic Sclerosis, Fibrosing Syndromes and Raynaud's - Pathogenesis, Animal Models and Genetics
Session Type: Abstract Submissions (ACR)
Background/Purpose: Systemic sclerosis (SSc) is a serious autoimmune disease with clinical phenotypes of different prognosis, progression rate, and different extent of involvement of internal organs. Specific circulating autoantibody profiles contribute to forecasting the prognosis of SSc cases. Circulating micro-RNA (miRNA) profiles also are characteristic in SSc but clinical phenotypes, autoantibody profiles, and circulating miRNA profiles have not yet been correlated. The aim of the study, therefore, was to evaluate the expression profiles of cell-free plasma miRNAs in SSc and study their correlation with disease subgroups (limited cutaneous SSc (lcSSc) and diffuse cutaneous SSc (dcSSc)) and with clinical and paraclinical parameters including circulating autoantibody profiles.
Methods: Total RNA was purified from plasma and the abundance of 45 mature miRNAs were measured using quantitative polymerase chain reaction assays after reverse transcription. A total of 95 SSc patients (n=94 fulfilling the ACR criteria for SSc, n=1 with limited SSc) were included (lcSSc, n=63; dcSSc, n=32). The patients represented the following autoantibody subgroups: anti-centromere group (ACA, n=35); anti-DNA topoisomerase I group (ATA, n=20), anti-RNA polymerase III group (ARA, n=20); and anti-U1-RNP group (RNP, n=20). MiRNA expression data, clinical data, autoantibody data, and other paraclinical data were analyzed for correlations. Regression analysis was performed to optimize models for prediction of SSc disease subgroups and autoantibody classes.
Results: A total of 36 miRNAs were measurable in all samples. Six of these miRNAs were statistically significantly differently expressed between the lcSSc and dcSSc groups in univariate tests and three (miRNAs -223, -181b, and 342-3p) remained significant after correction for multiple comparisons. Ten miRNAs exhibited statistically significant different levels in one or more autoantibody groups and three of these miRNAs were also found to differ between the dcSSc and lcSSc groups. Five miRNAs (miRNAs -409-3p, -184, -92a, -29a, and -101) retained significance after correction for multiple comparisons. Analysis of patterns of miRNA levels and clinical and paraclinal parameters showed correlations between C-reactive protein and glomerular filtration rates and the specific regulation of distinct miRNAs.
Conclusion: The profile of circulating miRNAs from plasma samples of SSc patients differ between patients classified as lcSSc and dcSSc and between the four autoantibody groups. Especially the ACA group is distinctive in terms of its specific circulating miRNA profile. This is the first time autoantibody profiles, disease phenotypes, and plasma miRNA profiles have been shown to correlate in an autoimmune disease. The data supports the role of miRNAs in SSc by showing that specific miRNAs are associated with autoantibody profiles of known diagnostic and prognostic value.
Disclosure:
D. Wuttge,
None;
A. L. Carlsen,
None;
G. Teku,
None;
S. Steen,
None;
M. Wildt,
None;
M. Vihinen,
None;
R. Hesselstrand,
None;
N. H. H. Heegaard,
None.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/specific-autoantibody-profiles-and-disease-subgroups-correlate-with-circulating-micro-rna-in-systemic-sclerosis/