Strong association of Torque teno virus/Torque teno-like minivirus to Kikuchi-Fujimoto lymphadenitis (histiocytic necrotizing lymphadenitis) on quantitative analysis

Introduction Kikuchi-Fujimoto disease (KFD) is a rare benign lymphadenitis that mainly involves cervical lymph nodes of young Asian women with unknown etiology. Recently, we experienced a case of KFD found with Torque teno virus/Torque teno-like mini virus (TTV/TTMV) from a 26-year-old woman. TTV/TTMV is a genus of Circoviridae that causes necrotizing lymphadenitis in pigs, which shares the key histologic finding of KFD. The purpose of this study is to investigate the pathogenic role of TTV/TTMV in KFD by quantitative polymerase chain reaction (qPCR) analysis. Method We performed two-step qPCR specific to TTV/TTMV with formalin-fixed paraffin-embedded tissue of sequentially selected 100 KFD patients and 50 randomly selected, matched normal controls. Consequent direct sequencing was done for confirmation with PCR products. Results PCR amplification of TTV and TTMV was found in a significantly higher proportion in KFDs than normal controls (TTV, 85% vs. 18%, p < 0.000; TTMV, 91% vs. 24%, p < 0.000). After the sequencing, KFD samples showed more sequence matching than control samples for TTMV (94% vs. 30%, p < 0.000). Conclusion This finding strongly suggests the possible implication of TTV/TTMV in the pathogenesis of KFD. Animal or in vivo experimental design should be followed in the future. Key Points • Kikuchi-Fujimoto disease (KFD) is rare and its etiology is still unclear. • Torque teno/Torque teno-like minivirus (TTV/TTMV) is a recently introduced virus in the Circoviridae family that causes necrotizing lymphadenitis in pigs, histologically similar to KFD. • We discovered the significantly increased TTV/TTMV viral loads in the KFD patients than normal controls, which implicates TTV/TTMV in the pathogenesis of KFD.