The role of human herpesvirus 6 (HHV-6) in connective tissue-related interstitial lung disease

Connective Tissue Diseases (CTD) are chronic inflammatory multisystemic rheumatic disease. In this disease, the respiratory system is frequently involved, expecially interstitial lung disease (ILD). Viruses are thought to play a role in the etiology of both connective tissue diseases and interstitial lung disase. Herpes viruses are also among the accused factors. In this study, we aimed to investigate the role of HHV-6 in interstitial lung disease due to Connective Tissue Diseases. 60 patients with CTD who applied to Gaziantep University Medical Faculty Rheumatology Outpatient Clinic and 26 healthy controls were included in the study. It consisted of 29 patients with CTD (non-ILD) and 31 patients with interstitial lung disease due to connective tissue disease (CTD-ILD). Serum samples were collected from all individuals participating in the study. In addition, sputum samples were taken from the patients in a sterile container. The study was carried out in Gaziantep University Faculty of Medicine Microbiology Laboratory. In serum samples, HHV-6 IgG antibodies were analyzed by ELISA method (Sunred Biological Technology, Shanghai, China). HHV-6 DNA was investigated by Real-Time PCR (Qiagen, Germany) method in all serum samples and sputum samples taken from patients In positive samples, to investigate the replication status of the virus, the U42 and U94 gene regions were evaluated by RT PCR using separate primers for mRNAs. The first PCR was performed to investigate the presence of the virus, and the second to investigate the latency of the virus and whether it was reactivated. In the study, when the HHV-6 IgG serum titers were compared between the healthy controls and CTD and CTD-ILD groups, no significant difference was found (p=0.108). HHV-6 DNA was not detected in the serum sample analyzes of the healthy control group. On the other hand, HHV-6 DNA (U94 and/or U42 positive) was found positive in 33 (55%) of the patient sera, and a statistically significant difference was found compared to the control group. (p=0.001). . There was no significant difference between CTD-ILD and CTD in terms of serum HHV-6 DNA positivity (p=0.979). Sputum HHV-6 DNA (U94 gene) positivity was detected in 14 (45.2%) patients in CTD-ILD and in 5 samples (17.2%) in CTD patients. Statistically, sputum HHV-6 DNA (U94 gene) positivity was found to be significantly higher in CTD-ILD (p=0.020). Among the HHV-6 DNA positive samples, only two patients were found to be positive for HHV-6 mRNA (U42 and U94) in their serum, and these patients who had CTD-ILD. The results of this study demostrate that interstitial lung disease due to connective tissue diseases may related to HHV-6. In addition this study show that more comprehensive studies are needed to better understand this relationship.