Background/Purpose: The detection of Ro52/TRIM21 autoantibodies has been considered an independent prognostic marker in different rheumatic conditions. However, the information about the expression of Ro52/TRIM21 in subsets of peripheral blood mononuclear cells (PBMCs) in autoimmune diseases is scant. Specifically, its role in idiopathic inflammatory myopathies (IIM) has not been elucidated, and the evaluation of its expression in these diseases is the aim of the present study. 

Methods: We included active, untreated patients with recent diagnosis (<1 month) of IIM according to Bohan and Peter’s criteria, who attended a tertiary care center from March 2013 to April 2014. Patients with diagnosis of dermatomyositis (DM), polymyositis (PM) and antisynthetase syndrome (AAS), as well as age and gender-matched healthy controls were recruited. All subjects gave informed consent and the study was approved by the institutional ethics committee. PBMCs were isolated by Ficoll-Hypaque method and different subsets of PBMCs (CD4⁺, CD8⁺, CD14⁺) were purified by magnetic selection. The expression of Ro52/TRIM21 was evaluated by Western Blot. Descriptive statistics are shown with mean and standard deviation. Student’s T test or Mann-Whitney U test was used to analyze differences between groups.

Results: We included 14 patients with IIM (1 PM, 3 AAS, 10 DM), as well as 14 healthy controls. Sixty percent of subjects were female, with a mean age of 43±15 years. CPK levels at diagnosis were 4534±2235 UI/L and lymphocyte count was 1021±170 cells/uL. The presence of myositis-specific and associated autoantibodies was assessed by ELISA. The autoantibodies found in DM patients were anti-Ro52 (20%) anti-PL7 (20%), anti-Ku (20%), anti-PL12 (10%), anti-SRP (10%) and anti-Mi2 (10%). In AAS patients, anti-Ro52 (33.3%), anti-Jo1 (33.3%) and anti-PMScl75 (33.3%) were identified. We did not find any specific nor associated autoantibodies in the patient with PM. Patients with IIM showed decreased protein expression of Ro52/TRIM21 in comparison to healthy controls in different PBMC subsets: total PBMC (0.971±0.603 vs 1.849±0.927, p=0.016), CD4⁺ lymphocytes (0.797±0.540 vs 2.413±0.786 p=0.017), and monocytes (0.875±0.358 vs 1.890±0.209 p<0.001). CD8⁺ lymphocytes from IIM patients also showed a trend towards lower Ro52/TRIM21 expression (0.902±0.708 vs1.610±0.540, p=0.133). We did not find significant differences among each of the IIM groups. 

Conclusion: Our findings suggest that patients with IIM are characterized by deficient expression of the ubiquitin ligase Ro52/TRIM21 in different PBMC subsets (CD4⁺ lymphocytes and monocytes). Further insights into the function of this protein will have profound implications for the understanding of its role in IIM. TRIM21 deficiency could be particularly related to decreased IRF ubiquitination and degradation, which could enhance type 1 interferon signaling.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/deficiency-of-ro52trim21-in-different-subsets-of-peripheral-blood-mononuclear-cells-from-patients-with-inflammatory-myopathies/