Anti-Ro52/TRIM21 is independently associated with pulmonary arterial hypertension and mortality in a cohort of systemic sclerosis patients

Lee, A. Y.S.; Patterson, Karen; Tan, Daniel J; Wilson, Michelle; Proudman, Susanna; Stevens, Wendy; Nikpour, Mandana; Sahhar, Joanne; Ngian, Gene‐Siew; Roddy, Janet; Roberts‐Thomson, Peter; Walker, Jenny

doi:10.1080/03009742.2021.1887927

Cited by 16 publications

(10 citation statements)

References 21 publications

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“…In our cohort, Ro52 positivity was associated with presence of PAH. This association has also been discovered by others (21,74,75,78).Others have reported an association between Ro52 and ILD (79). However, Patterson et al (21) or Lee et al (78) were not able to replicate these findings.…”

Section: Discussionsupporting

confidence: 81%

“…This association has also been discovered by others (21,74,75,78).Others have reported an association between Ro52 and ILD (79). However, Patterson et al (21) or Lee et al (78) were not able to replicate these findings. In our study, we were neither able to find this association.…”

Section: Discussionsupporting

confidence: 81%

“…( 21 ) or Lee et al. ( 78 ) were not able to replicate these findings. In our study, we were neither able to find this association.…”

Section: Discussionmentioning

confidence: 88%

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Comprehensive autoantibody profiles in systemic sclerosis: Clinical cluster analysis

Höppner

Tabeling²,

Casteleyn³

et al. 2023

Front. Immunol.

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BackgroundSystemic sclerosis (SSc) belongs to the group of connective tissue diseases and is associated with the occurrence of disease-specific autoantibodies. Although it is still controversial whether these antibodies contribute to pathogenesis, there are new insights into the development of these specific antibodies and their possible pathophysiological properties. Interestingly, they are associated with specific clinical manifestations, but for some rarer antibodies this association is not fully clarified. The aim of this study is a comprehensive analysis of the serum autoantibody status in patients with SSc followed by correlation analyses of autoantibodies with the clinical course of the disease.MethodsSerum from SSc patients was analyzed using a line blot (EUROLINE, EUROIMMUN AG) for SSc-related autoantibodies. Autoantibodies to centromere, Topo-1, antimitochondrial antibodies (AMA) M2 subunit, angiotensin II type 1 receptors (AT1R) and endothelin-1 type-A-receptors (ETAR) were also determined by ELISA. We formed immunological clusters and used principal components analysis (PCA) to assign specific clinical characteristics to these clusters.ResultsA total of 372 SSc patients were included. 95.3% of the patients were antinuclear antibody positive and in 333 patients at least one SSc specific antibody could be detected. Four immunological clusters could be found by PCA. Centromere, Topo-1 and RP3 all formed own clusters, which are associated with distinct clinical phenotypes. We found that patients with an inverted phenotype, such as limited cutaneous SSc patients within the Topo-1 cluster show an increased risk for interstital lung disease compared to ACA positive patients. Anti-AT1R and anti-ETAR autoantibodies were measured in 176 SSc patients; no association with SSc disease manifestation was found. SSc patients with AMA-M2 antibodies showed an increased risk of cardiovascular events.ConclusionIn our in large cluster analysis, which included an extended autoantibody profile, we were able to show that serologic status of SSc patients provides important clues to disease manifestation, co-morbidities and complications. Line blot was a reliable technique to detect autoantibodies in SSc and detected rarer autoantibodies in 42% of our patients.

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Section: Discussionsupporting

confidence: 81%

Section: Discussionsupporting

confidence: 81%

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Comprehensive autoantibody profiles in systemic sclerosis: Clinical cluster analysis

Höppner

Tabeling²,

Casteleyn³

et al. 2023

Front. Immunol.

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“…21,82 79,80 Others have reported an association between Ro52 and ILD. 83 However, Patterson et al 21 or Lee et al 82 were not able to replicate these findings. In our study, we were neither able to find this association.…”

Section: Discussionmentioning

confidence: 96%

Comprehensive Autoantibody Profiles in Systemic Sclerosis: Clinical Cluster Analysis

Höppner

Tabeling

Casteleyn

et al. 2022

Preprint

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Background: Systemic sclerosis (SSc) belongs to the group of connective tissue diseases and is associated with the occurrence of disease-specific autoantibodies. Although it is still controversial whether these antibodies contribute to pathogenesis, there are new insights into the development of these specific antibodies and their possible pathophysiological properties. Interestingly, they are associated with specific clinical manifestations, but for some rarer antibodies this association is not fully clarified. The aim of this study is a comprehensive analysis of the serum autoantibody status in patients with SSc followed by correlation analyses of autoantibodies with the clinical course of the disease. Methods: Serum from SSc patients was analyzed using a line blot (EUROLINE, EUROIMMUN AG) for SSc-related autoantibodies. Autoantibodies to centromere, Topo-1, antimitochondrial antibodies (AMA) M2 subunit, angiotensin II type 1 receptors (AT1R) and endothelin-1 type-A-receptors (ETAR) were also determined by ELISA. We formed immunological clusters and used principal components analysis (PCA) to assign specific clinical characteristics to these clusters. Results: A total of 372 SSc patients were included. 95.3% of the patients were antinuclear antibody positive and in 333 patients at least one SSc specific antibody could be detected. Four immunological clusters could be found by PCA. Centromere, Topo-1 and RP3 all formed own clusters, which are associated with distinct clinical phenotypes. We found that patients with an inverted phenotype, such as limited cutaneous SSc patients within the Topo-1 cluster show an increased risk for ILD compared to ACA positive patients. Anti-AT1R and anti-ETAR autoantibodies were measured in 176 SSc patients; no association with SSc disease manifestation was found. SSc patients with AMA-M2 antibodies showed an increased risk of cardiovascular events. Conclusion: In our in large cluster analysis, which included an extended autoantibody profile, we were able to show that serologic status of SSc patients provides important clues to disease manifestation, co-morbidities and complications. Line blot was a reliable technique to detect autoantibodies in SSc and detected rarer autoantibodies in 42% of our patients.

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“…The autoantibody is not disease-specific and may be found in a range of systemic autoimmune diseases (SADs) such as Sjögren’s syndrome (SS) and organ-specific autoimmune disorders, such as primary biliary cirrhosis (PBC) [ 2 ]. Nevertheless, anti-Ro52/TRIM21 IgG has clinical utility and may be a useful prognostic marker of severity in a number of SADs such inflammatory myositides and systemic sclerosis [ 3 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

Anti-Ro52/TRIM21 serological subsets identify differential clinical and laboratory parameters

2022

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Introduction Anti-Ro52/tripartite motif-containing protein 21 (TRIM21) IgG is one of the most common autoantibodies found in systemic autoimmune diseases and is typically found in conjunction with anti-Ro60 and/or anti-La. A retrospective, cross-sectional study was undertaken to examine the clinical and laboratory features of two serological subsets: patients with anti-Ro52/TRIM21 autoantibodies in the absence of anti-Ro60 and anti-La (isolated anti-Ro52/TRIM21) and patients with anti-Ro52/TRIM21 in the presence of anti-Ro60 and/or anti-La. Methods Over a 12-month period, patients tested positive for anti-Ro52/TRIM21 via line immunoassay (LIA) at the Westmead Hospital (Australia) immunopathology laboratory were included. The presence of anti-Ro60 and/or anti-La via same LIA was noted. Associated laboratory and medical records were perused to extract demographic, laboratory, and clinical information. Results There were 346 patients within the study period, and 39.9% of the patients positive for anti-Ro52/TRIM21 lacked anti-Ro60/anti-La autoantibodies. Isolated anti-Ro52/TRIM21 patients tend to be older, have lower anti-Ro52/TRIM21 titres, have lower rheumatoid factors, and have lower proportions of neutropaenia compared to patients who were positive for anti-Ro52/TRIM21 and anti-Ro60/La. This occurred independent to diagnoses of Sjögren’s syndrome or systemic lupus erythematosus. Coexisting neurological syndromes, pulmonary pathologies, and malignancies were more prevalent in the isolated anti-Ro52/TRIM21 subset. Conclusions Patients with isolated anti-Ro52/TRIM21 tend to have distinct and important clinical and laboratory associations. It is unclear if these patients evolve or remain a stable subset and how they originate immunologically. Longitudinal and prospective studies are required to ascertain the overall predictive and prognostic value of this stratification. Key Points• Anti-Ro52/TRIM21 is an autoantibody found in autoimmunity and non-immunological conditions.• Sixty percent of anti-Ro52/TRIM21 patients are positive for anti-Ro60.• Isolated anti-Ro52/TRIM21 has reduced anti-Ro52/TRIM21 and rheumatoid factor titres.• Isolated anti-Ro52/TRIM21 is associated with anaemia and malignancies.

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Anti-Ro52/TRIM21 is independently associated with pulmonary arterial hypertension and mortality in a cohort of systemic sclerosis patients

Cited by 16 publications

References 21 publications

Comprehensive autoantibody profiles in systemic sclerosis: Clinical cluster analysis

Comprehensive autoantibody profiles in systemic sclerosis: Clinical cluster analysis

Comprehensive Autoantibody Profiles in Systemic Sclerosis: Clinical Cluster Analysis

Anti-Ro52/TRIM21 serological subsets identify differential clinical and laboratory parameters

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