Viral load of Torquetenovirus correlates with Sano’s score and levels of total bilirubin and aspartate aminotransferase in Kawasaki disease

Abstract

Cause of Kawasaki disease (KD) is unknown. KD is often resistant to treatment with intravenous immunoglobulin (IVIG). Sano’s score, which is derived from total bilirubin (TBIL), aspartate aminotransferase (AST) and C-reactive protein (CRP), is predictive of IVIG resistance in Japan. A recent study reported that Torquetenovirus (TTV), especially TTV7, was present at a high viral load in the patients with KD. We used PCR to quantify TTV load and amplicon next generation sequencing to detect individual TTV species. We used serum samples that were collected between 2002 and 2005 from 57 Japanese KD patients before IVIG treatment. Correlations between TTV load and Sano’s score, the biomarkers that constitute this score, and IVIG resistance were examined. TTV load was positively correlated with Sano’s score (P = 0.0248), TBIL (P = 0.0004), and AST (P = 0.0385), but not with CRP (P = 0.6178). TTV load was marginally correlated with IVIG resistance (P = 0.1544). Presence of TTV7 was correlated with total TTV load significantly (P = 0.0231). The correlations between biomarkers for KD and TTV load suggested that TTV may play a role in the pathophysiology of KD. We hypothesize that TTV7 may be associated with a higher total viral load in KD.

Torque Teno Virus (TTV) in Renal Transplant Recipients: Species Diversity and Variability

“…However, we were able to demonstrate that a combination of techniques like RCA, UAvI-PCR and NGS is a valuable tool for obtaining whole-genome TTV sequences. This combination was previously used by Spezia et al, 2023 [ 29 ] to successfully identify TTV species in patients with Kawasaki disease. These tools will contribute to a deeper understanding of TTV viral epidemiology due to the small number of studies currently available.…”

“…A whole-genome, amplicon-based, next-generation sequencing (NGS) technique was used to detect individual TTV species, as previously described [ 29 ].…”

“…According to the previous International Committee on Taxonomy of Viruses (ICTV) guidelines, the 29 TTV species described were divided into five genogroups: genogroup I (TTV 1-5), genogroup II (TTV 6-8), genogroup III (TTV [13][14][15][16][17][18][19][20][21][22][23][24], genogroup IV (TTV [25][26][27][28][29] and genogroup V (TTV 9-12). In the latest ICTV update, TTV species were recategorized into 22 species, based on a sequence identity threshold of 69% for the ORF1 coding region [11].…”

Emerging evidence of microbial infection in causing systematic immune vasculitis in Kawasaki disease

“…The torque teno virus (TTV), which is a single-stranded circular DNA virus, was first found in the lymph node of a KD patient ( Katano et al, 2012 ). For instance, a high viral load of torque teno virus 7 (TTV7) was identified in KD patients ( Thissen et al, 2018 ; Spezia et al, 2023a ), and the viral load of TTV positively correlated with the level of total bilirubin and aspartate aminotransferase in KD patients ( Spezia et al, 2023b ), suggesting that TTV might play a critical role in the pathophysiology of patients with KD.…”