- The study addressed the lack of clarity and precision in the literature regarding autoantibodies against Telomerase RNA Ro y-RNAs and Vault RNAs Domain Family Member 2 (TROVE2)/Ro60 and Tripartite Motif 21 (TRIM21)/Ro52.
- Researchers conducted a systematic review of 891 publications (301 systemic lupus erythematosus, 493 Sjögren disease, 97 mixed) followed by a Delphi consensus process with 17 international experts.
- The review found that only 20.9% of studies tested and reported these autoantibodies separately, with 16 different terms for anti-TROVE2/Ro60 and 11 for anti-TRIM21/Ro52.
- The authors concluded that the distinction and clinical associations of anti-TROVE2/Ro60 and anti-TRIM21/Ro52 autoantibodies were frequently unclear and imprecise in the literature.
- To enhance understanding, the terms anti-TROVE2/Ro60 and anti-TRIM21/Ro52 autoantibodies are recommended for future studies and publications to clarify clinical associations.
Clarifying Autoantibody Terminology in Autoimmune Disease
The identification of specific autoantibodies is a cornerstone in the diagnosis and management of systemic autoimmune diseases, offering crucial prognostic information and guiding therapeutic choices [1, 2]. While the presence of certain autoantibodies can predate clinical symptoms by years, their full clinical utility depends on precise and consistent reporting [2]. Unfortunately, inconsistent terminology and testing practices can obscure important distinctions between different autoantibodies, hindering a clear understanding of their specific roles in disease [3, 4, 5]. A recent consensus statement, informed by a comprehensive literature review, addresses this challenge for two frequently confused autoantibodies central to rheumatology.
The Challenge of Ambiguous Autoantibody Reporting
The focus of the expert consensus was on autoantibodies directed against two distinct proteins: Telomerase RNA Ro y-RNAs and Vault RNAs Domain Family Member 2, or TROVE2/Ro60, and Tripartite Motif 21, or TRIM21/Ro52. Although modern laboratory methods allow for their separate detection, these two autoantibodies are often conflated under the historical umbrella of SSA/Ro autoantigens. This persistent confusion in both clinical and research settings has created significant imprecision in the medical literature. Failing to consistently distinguish between anti-TROVE2/Ro60 and anti-TRIM21/Ro52 obscures their individual clinical associations, which may differ in conditions like systemic lupus erythematosus (SLE) and Sjögren disease (SjD), thereby limiting their potential value for diagnosis, prognosis, and patient stratification.
Systematic Review Reveals Widespread Inconsistency
To quantify the extent of this problem, an international group of experts began by conducting a systematic literature review. The analysis methodically searched for primary publications on SLE and SjD published between January 1, 2000, and May 26, 2025, that mentioned testing for either autoantibody. The review captured a total of 891 publications, comprising 301 on SLE, 493 on SjD, and 97 on mixed patient cohorts. The findings confirmed a profound lack of standardized reporting. A striking 75.0% of studies failed to test for and report the two autoantibodies separately, while only 20.9% did so. Another 4.2% of studies performed separate tests but did not report the results distinctly. This inconsistency was further complicated by what the authors termed nomenclatural heterogeneity, a confusing variety of names for the same markers. The review identified 16 different terms used for anti-TROVE2/Ro60 and 11 different terms for anti-TRIM21/Ro52, highlighting a critical barrier to clear communication and data synthesis.
Expert Consensus for Clearer Clinical Communication
The systematic review's findings provided the foundation for a Delphi consensus exercise, a structured process designed to achieve expert agreement through iterative rounds of discussion and voting. The panel consisted of 17 international physicians and laboratory scientists with expertise in autoimmune disease. After two rounds of voting, the panel reached a unanimous decision. They recommend the specific terms anti-TROVE2/Ro60 and anti-TRIM21/Ro52 autoantibodies for all future use. The authors argue that adopting this precise nomenclature is essential for clinical practice. It will enable the medical community to clarify the distinct clinical associations of each autoantibody, potentially improving diagnostic accuracy, prognostic assessments, and the ability to compare findings across studies. This standardization is presented as a necessary step to strengthen the clinical utility of these two important biomarkers in patient care.
References
1. Choi MY, FitzPatrick RD, Buhler KA, Mähler M, Fritzler MJ. A review and meta-analysis of anti-ribosomal P autoantibodies in systemic lupus erythematosus. Autoimmunity Reviews. 2020. doi:10.1016/j.autrev.2020.102463
2. Arbuckle MR, McClain MT, Rubertone MV, et al. Development of Autoantibodies before the Clinical Onset of Systemic Lupus Erythematosus. New England Journal of Medicine. 2003. doi:10.1056/nejmoa021933
3. Wingerchuk DM, Banwell B, Bennett JL, et al. International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology. 2015. doi:10.1212/wnl.0000000000001729
4. Keeling D, Mackie I, Moore G, Greer IA, Greaves M. Guidelines on the investigation and management of antiphospholipid syndrome. British Journal of Haematology. 2012. doi:10.1111/j.1365-2141.2012.09037.x
5. Aletaha D, Neogi T, Silman AJ, et al. 2010 Rheumatoid arthritis classification criteria: An American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis & Rheumatism. 2010. doi:10.1002/art.27584