High Prevalence of Immunoglobulin A Antibody Against Epstein-Barr Virus Capsid Antigen in Adult Patients with Lupus with Disease Flare: Case Control Studies

CHUNG-JEN CHEN, KUEI-HSIANG LIN, SHIH-CHANG LIN, WEN-CHAN TSAI, JENG-HSIEN YEN, SHUN-JEN CHANG, SHENG-NAN LU, and HONG-WEN LIU

ABSTRACT.

Objective. Systemic lupus erythematosus (SLE) is a severe autoimmune disease with rare remission and recurrent flare. Epstein-Barr virus (EBV) infection has been reported to be strongly associated with SLE in the United States, but with an inconclusive role in Asia. We investigated the role of EBV infection in patients with SLE in Taiwan, with one of the highest population densities in Asia.

Methods. We conducted case-control studies to test whether EBV infection was associated with adult SLE in Taiwan. In the first study, 36 adults with SLE and 36 sex and age matched controls were enrolled for examination of serum IgG, IgM, and IgA antibody against EBV-virus capsid antigen (EBV-VCA). In the second study, another 36 adult lupus cases and 36 matched controls were enrolled to confirm the high prevalence of IgA antibody against EBV-VCA found in the first study. Further, both groups of SLE patients were combined to analyze the association between the existence of IgA antibody against EBV-VCA and disease activity (determined by SLEDAI score) and disease flare in patients with SLE.

Results. In the first study, IgA antibody against EBV-VCA was the only marker with significantly higher prevalence in adults with SLE compared to healthy adults (36.1% vs 5.6%; p < 0.005). In the second study, we confirmed that the prevalence of IgA antibody against EBV-VCA was indeed higher in adults with SLE (38.9% vs 2.8%; p < 0.001). With further analysis (pooling analysis), adult SLE patients with IgA antibody against EBV-VCA had higher disease activity compared to SLE patients without IgA antibody against EBV-VCA (SLEDAI 7.8 ± 6.6 vs 3.3 ± 2.1; p < 0.001). SLE patients with flare showed much higher prevalence of IgA antibody against EBV-VCA compared to those without flare (81.3% vs 25.0%; p < 0.001).

Conclusion. This is the first evidence that IgA antibody against EBV-VCA is strongly associated with disease flare in SLE patients. It suggests that EBV reactivation may contribute toward the disease flare of SLE. (J Rheumatol 2005;32:44-7)

Key Indexing Terms:

SYSTEMIC LUPUS ERYTHEMATOSUS
FLARE
EPSTEIN-BARR VIRUS
REACTIVATION

---

From the Department of Internal Medicine and Department of Clinical Laboratory, Kaohsiung Medical University, Kaohsiung; Department of Internal Medicine, Chang Gung Memorial Hospital at Kaohsiung, Kaohsiung Hsien; and Department of Internal Medicine, Cathay General Hospital, Taipei, Taiwan.

Supported by Yu-Zu Memorial Prize for Lupus Research, Kaohsiung Medical University (Grant No. KMU 92-A-03), and Chang Gung Memorial Hospital (Grant No. BMRP743).

C. Chen, MD, Associate Professor, Department of Internal Medicine, Chang Gung Memorial Hospital at Kaohsiung; K. Lin, PhD, Associate Professor, Department of Clinical Laboratory, Kaohsiung Medical University; S. Lin, MD, PhD, Assistant Professor, Department of Internal Medicine, Cathay General Hospital; W. Tsai, MD, PhD, Associate Professor, Department of Internal Medicine, Kaohsiung Medical University; J. Yen, MD, PhD, Professor, Department of Internal Medicine, Kaohsiung Medical University; S. Chang, PhD, Associate Professor, Department of Public Health, Kaohsiung Medical University; S. Lu, MD, PhD, Associate Professor, Department of Internal Medicine, Chang Gung Memorial Hospital at Kaohsiung; H. Liu, MD, Professor, Department of Internal Medicine, Kaohsiung Medical University.

Address reprint requests to Prof. H.W. Liu, Department of Internal Medicine, Kaohsiung Medical University, No. 100, Shih-Chuan 1st Road, Kaohsiung, Taiwan 80708. E-mail: liuhow@kmu.edu.tw

Submitted September 23, 2003; revision accepted August 13, 2004.

---