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Increased antibodies to Epstein–Barr virus and cytomegalovirus in patients with drug-induced lupus indicate their contribution to the development of the disease.

EpsteinBarr virus (EBV) and cytomegalovirus (CMV) are implicated in systemic lupus erythematosus (SLE) pathogenesis. Drug-induced lupus (DIL) is a lupus-like disease resulting from therapeutic drug intake. DIL represents approximately 1015% of all lupus cases. It has yet to be determined whether EBV and CMV infections contribute to the development of DIL. 

A study published in the journal Viruses assessed the presence of antibodies to EBV and CMV in DIL patients to determine if these viral infections are linked to the onset of DIL. In the study, sera from patients of DIL and drug-induced vasculitis (DIV) were collected. DIV sera were used as negative lupus controls. Sera from SLE patients and healthy controls (HCs) were also obtained. 

CMV pp52 and recombinant EBV early antigen–diffuse (EA/D) IgG levels in patient and control sera were assessed by direct enzyme-linked immunosorbent assay (ELISA). In total, 40 HC, 30 SLE, and 40 DIL samples were analyzed for reactivity to CMV pp52. The same samples and 20 DIV samples were tested for reactivity to EBV EA/D.

IgG Titers in Lupus Patients and Controls

Elevated IgG titers to both EBV EA/D and CMV pp52 were found in DIL and SLE serum samples compared to HCs. As a result, a virus-specific IgG correlation analysis was performed between the two disease groups; however, no correlation was established between EA/D and CMV pp52 IgG in the SLE and DIL samples.

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Total IgG and Antibody Concentrations in Autoimmune Diseases and Controls

Competitive ELISA was used to analyze individual DIL, DIV, SLE, and HC serum samples to determine the total IgG levels. DIL samples showed significantly lower total IgG levels than HCs (p = 0.0048) and SLE samples (p = 0.0177). The total IgG levels in the DIV samples were significantly reduced compared to HCs (p = 0.0130), but not when compared to DIL and SLE samples (p > 0.05).

Elevated EBV EA/D and CMV pp52 IgG Levels Observed

Subsequently, antibody concentrations normalized relative to mg IgG were analyzed. The pattern appeared to be independent of the total IgG concentrations. DIL and SLE samples showed significantly elevated EBV EA/D and CMV pp52 IgG levels compared to HCs. Similarly, significantly decreased EBV EA/D IgG concentrations were detected in DIV samples compared to SLE samples.

This study suggests a significant relationship between EBV, CMV, and DIL, as evidenced by elevated antibodies to viral antigens. A larger prospective study in the future would help to consolidate these findings.


Knudsen, J., Trier, N. H., Draborg, A. H., Nielsen, C. T., Jacobsen, S., Højrup, P., & Houen, G. (2023). Elevated Antibody Titers to Epstein–Barr Virus and Cytomegalovirus in Patients with Drug-Induced Lupus. Viruses, 15(4), 986. https://doi.org/10.3390/v15040986