Polymyositis/dermatomyositis and nasopharyngeal carcinoma: The Epstein–Barr virus connection?

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Abstract

Background

Polymyositis (PM) and dermatomyositis (DM) are associated with high risk of nasopharyngeal carcinoma (NPC) in Asian countries. Epstein–Barr virus (EBV) might induce autoimmunity and malignancies in susceptible individuals.

Objectives

To investigate the association of EBV with PM/DM and NPC in PM/DM patients.

Study design

Serum levels of anti-EBV viral capsid antigens (VCA) and anti-EBV-coded nuclear antigens-1 (EBNA-1) antibodies were measured by ELISA, and EBV DNA loads were determined using real-time PCR for 98 PM/DM patients, 94 systemic lupus erythematosus (SLE) patients and 370 healthy controls (HC). Anti-transfer-RNA synthetase antibodies (ASA) were determined by radioimmunoprecipitation for PM/DM patients.

Results

Thirteen (13.3%) of PM/DM patients vs. none of SLE patients had detectable NPC. ASA were detectable in 31.7% of PM/DM without malignancy, while lack of ASA in any PM/DM patient with NPC. IgA anti-EBNA-1 were detectable in 30.6% of PM/DM patients and 31.9% of SLE patients, but only in 4.1% of HC (odds ratio [OR] 10.44 and 11.12 respectively, both p < 0.001). Significantly higher positivity for IgA anti-EBNA-1 were observed in PM/DM with NPC than in those without malignancy (OR 44.7, p < 0.01). Significantly higher positivity for EBV genome were observed in PM/DM with NPC than in those without malignancy (OR 43.9, p < 0.01), in SLE patients (OR 13.2, p < 0.05) and in HC (OR 99.4, p < 0.001). EBV DNA loads were significantly higher in PM/DM with NPC compared with those without malignancy and HC.

Conclusions

Our results showed a positive association of EBV with PM/DM and NPC. PM/DM patients who have IgA anti-EBNA-1 or increased EBV DNA loads should be highly suspected to have occult NPC.

Section snippets

Background

Polymyositis (PM)/dermatomyositis (DM) are inflammatory muscular diseases,1, 2 and are the outcome of autoimmunity that results in injuries to muscle fibers.3, 4, 5 The best defined myositis-specific autoantigens are transfer RNA-synthase, and the prevalence of anti-synthetase antibodies (ASA) is up to 20–37% in PM/DM patients.6, 7 However, the etiopathogenesis of PM/DM remains unclear.

Viral infection might induce autoimmunity in susceptible individuals.8, 9 The reported seasonal occurrence of

Objectives

This study is the first attempt to investigate the associations of EBV infection with clinical manifestations and the occurrence of NPC in PM/DM patients. We re-examine the association between EBV infection and PM/DM using serologic assays for IgA anti-EBNA-1 antibody responses to a fragment of EBNA-1 lacking cross-reactive epitopes, and using real-time quantitative polymerase chain reaction (RQ-PCR) to determine EBV DNA loads. To test whether the emergence of NPC in myositis patients was the

Patients and matched controls

Ninety-eight adult patients fulfilling the Bohan and Peter criteria of PM/DM30, 31 were enrolled. After investigation, all patients were treated with corticosteroids and immunosuppressive agents. Ninety-four consecutive patients fulfilling the 1997 revised criteria for SLE32 and continuously receiving immunosuppressant were enrolled as disease control. Three hundred and seventy healthy volunteers who had no rheumatic disease or malignancy served as healthy controls (HC) by matching for sex and

Clinical characteristics and laboratory findings

Thirteen (13.3%) PM/DM patients had a detectable NPC, while none of SLE patients developed NPC during the 10-year follow-up period. As illustrated in Table 1, significantly lower proportion of females and interstitial lung disease was observed in PM/DM patients with NPC compared with those without malignancy. Interestingly, a lack of detectable ASA was observed in any myositis patient with NPC. There were no significant differences in the mean doses of daily corticosteroids or the proportion of

Discussion

The etiology of PM/DM remains unclear, but various causative factors including autoantibodies, genetic susceptibility, and viral infection have been postulated.3, 35, 36, 37, 4, 5, 6, 7, 8 The role of EBV infection in PM/DM was suspected.37, 8 We showed a significantly higher positive rate for IgA anti-EBV EBNA-1 and EBV DNA genome in sera of PM/DM patients compared with HC, which supports an association of EBV with myositis. Similarly, significantly higher positive rates for IgA anti-EBV

Conflict of interest

None.

Acknowledgements

Funding: This study was supported by Taichung Veterans General Hospital and National Taichung Nursing College, Taiwan (Grant TCVGH-NTCNC-978502).

Competing interests: None declared.

Ethical approval: The study protocol was approved by the Ethics Committee of Taichung Veterans General Hospital.

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