{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T11:29:52Z","timestamp":1786361392806,"version":"build-2736575974"},"reference-count":44,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T00:00:00Z","timestamp":1786147200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"publisher","award":["101095052"],"award-info":[{"award-number":["101095052"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"award":["101095052"],"award-info":[{"award-number":["101095052"]}],"id":[{"id":"https:\/\/ror.org\/019w4f821","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Med. Sci.","Medical Sciences"],"abstract":"<jats:p>Background\/Objectives: Torque teno virus (TTV) is small non-pathogenic virus, currently under investigation as a potential biomarker to monitor immunocompetence in patients with rheumatoid arthritis (RA) receiving various immunosuppressive therapies. To allow for large-scale assessment of existing pan-European RA cohorts, minimal specimen (serum) input for TTV DNA detection through quantitative PCR (qPCR) needs to be identified in relation to the type and quantity of immunosuppression. Methods: TTV qPCR analysis was performed by measuring 1:1, 1:2, 1:4 and 1:8 dilutions of 278 human serum samples derived from patients with RA under different therapies. The smallest detectable difference (SSD) as well as the intra-class correlation (ICC) were assessed. The reproducibility of results was determined by measuring an additional 19 sample duplicates. Results: RA patient sera showed a mean TTV viral load equivalent of 2.9 log10 genome copies\/mL (SD \u00b1 1.47). A total of 32 samples (11.6%) were negative for TTV; 54 (19.6%) were below 2.4 log10, the manufacturer\u2019s lower limit of quantification; 44 (16%) were between 2.4 and 3.0 log10; and 145 (52.7%) showed a high viral load above 3.0 log10. Dilution and replication experiments showed a high stability and reproducibility of TTV measurements (overall ICC: 0.95 (95%CI: 0.951 to 0.966)). TTV differed between undiluted and 4-fold- as well as 8-fold-diluted samples (1 vs. 2: p = 0.993; 1 vs. 4: p &lt; 0.001; 1 vs. 8: p &lt; 0.001), aligned with decreasing ICC and less sensitivity. RA disease activity did not influence reproducibility. Conclusions: Quantitative TTV DNA detection in serum samples from RA patients yields highly reproducible results, including 2-fold-diluted serum samples.<\/jats:p>","DOI":"10.3390\/medsci14040467","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T09:24:53Z","timestamp":1786353893000},"page":"467","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Reproducibility and Potential for Input Reduction for Torque Teno Virus DNA Quantification in Rheumatoid Arthritis"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8895-6941","authenticated-orcid":false,"given":"Paul","family":"Studenic","sequence":"first","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine III, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaimae","family":"Akile","sequence":"additional","affiliation":[{"name":"LUCID Department of Medical Microbiology & Infection Prevention, Leiden University Medical Center, 2300 RC Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4227-052X","authenticated-orcid":false,"given":"Claudia Anna","family":"Hana","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine III, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1281-2295","authenticated-orcid":false,"given":"Daniela","family":"Sieghart","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine III, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4340-8519","authenticated-orcid":false,"given":"Thi Lan Vi","family":"Tran","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine III, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josef","family":"Baliko","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine III, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-1853-0065","authenticated-orcid":false,"given":"Francois","family":"Bonnay","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine III, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7285-7124","authenticated-orcid":false,"given":"Souzi","family":"Makri","sequence":"additional","affiliation":[{"name":"Cyprus League of People with Rheumatism, Nicosia 1056, Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Aletaha","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine III, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5993-9846","authenticated-orcid":false,"given":"Mariet C. W.","family":"Feltkamp","sequence":"additional","affiliation":[{"name":"LUCID Department of Medical Microbiology & Infection Prevention, Leiden University Medical Center, 2300 RC Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1136\/ard.60.8.806","article-title":"Prevalence of TTV DNA and GBV-C RNA in patients with systemic sclerosis, rheumatoid arthritis, and osteoarthritis does not differ from that in healthy blood donors","volume":"60","author":"Seemayer","year":"2001","journal-title":"Ann. Rheum. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1016\/j.cmi.2016.04.007","article-title":"Torquetenovirus: The human virome from bench to bedside","volume":"22","author":"Focosi","year":"2016","journal-title":"Clin. Microbiol. 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