Torque Teno Virus quantification for monitoring of immunomodulation with biologic compounds in the treatment of rheumatoid arthritis

Abstract

Objectives Rheumatoid arthritis (RA) patients who fail to respond to methotrexate (MTX) can receive biologic disease-modifying antirheumatic drugs (bDMARDs). The Torque Teno Virus (TTV) is a potential novel candidate for monitoring of immunosuppression. We explore TTV in these patients and association with clinical response to bDMARDs. Methods The BioBio Study is a multicentre randomized open-label trial, including RA patients with insufficient response to MTX. Patients were randomized to either TNFi (infliximab, INF), anti-IL-6 (tocilizumab, TCZ), CTLA4-Ig (abatacept, ABA) or anti-CD20 (rituximab, RTX) in addition to MTX. PCR was used to quantify TTV in the peripheral blood. Results TTV was measured in 95 patients (INF, n = 23; TCZ, n = 22; ABA, n = 27; RTX; n = 23). TTV increased by a median of 4.5*104 copies/ml (c/ml; inter quartile range [IQR] 0–7.5*105) after 3 months. TTV levels at month 3 were associated with SDAI (p= 0.03) and CDAI response (p= 0.026) at month 6. A TTV cut-off level of 1.2*106 c/ml at month 3 had a positive likelihood ratio of 2.7 for prediction of SDAI85% response at month 6. Conclusion Our data suggest that TTV levels increase upon TNF, CD20 and co-stimulation blockade and associate with clinical response to bDMARDs in RA patients. Trial registration ClinicalTrials.gov; https://clinicaltrials.gov; NCT01638715

Obesity is associated with a higher Torque Teno viral load compared to leanness

“…Following our primary hypothesis, the main finding of the present study was a linear, robust and independent association between obesity and TTV load. TTV is known to associate with the hosts’ immune function ( 12 , 14 , 16 – 18 , 22 , 34 , 35 ). Thus, the high TTV load described in our cohort of individuals with obesity might reflect a compromised immune response.…”

“…Thus, TTV load might indirectly reflect the function of the immune system. Besides T cell function, TTV might also reflect other major domains of adaptive and innate immunity, including B cells, antigen presenting cells, natural killer cells, toll-like receptor antigen recognition, interferon alpha, and the complement system ( 17 – 22 ). Intriguingly, studies in the general aging population show that TTV load inversely associates with CD3+ and CD4+ T-cell counts and positively associates with mortality ( 21 , 23 ).…”

SARS-CoV-2 IgG spike protein antibody response in mRNA-1273 Moderna® vaccinated patients on maintenance immunoapheresis – a cohort study

“…Our study cohort comprises a mixed repertoire of immunocompromised patients, either due to comorbidities, such as liver or metabolic disease, or due to additional immunosuppressive medications. TTV, a highly prevalent and non-pathogenic small nonenveloped DNA virus, is an emerging marker to monitor immunosuppression in recipients of solid organ transplantations ( 17 , 20 ) and in patients with rheumatologic disease ( 21 ). Moreover, TTV is associated with immunocompetence in patients with HIV ( 22 ) and with response to SARS-CoV-2 vaccination in immunocompromised patients ( 18 , 23 ).…”

Integrated Immunologic Monitoring in Solid Organ Transplantation: The Road Toward Torque Teno Virus-guided Immunosuppression

“…53 Disease-modifying drugs (eg, anti-CD20) have been shown to increase TTV load in patients with rheumatoid arthritis, thereby suggesting that B cells contribute to TTV control. 54 Toll-like receptor TTV antigenrecognition 55 and interferon-α has been suggested to limit TTV replication. [56][57][58] Viral immune evasion is partly based on the ability of ORF2 to interfere with the host's inflammatory response via the suppression of NF-κB translocation.…”