Patients with active systemic lupus erythematosus (SLE) and receiving immunosuppressive therapy are at risk of developing cytomegalovirus (CMV) infection due to an attenuated CMV-specific immune response, according to the results of a study published in Open Forum Infectious Diseases. In individuals with active autoimmune disease, CMV has emerged as a source of opportunistic infection, and CMV-specific cell-mediated immunity is vital for controlling the infection.

Investigators prospectively monitored adult patients with active SLE and receiving intensive immunosuppressive therapy for clinically significant CMV infection by quantifying CMV DNA loads in plasma samples. CMV-specific T-cell responses were measured via the QuantiFERON-CMV (QF) assay, and results were either reactive (QF-positive), nonreactive (QF-negative), or indeterminate (also QF-negative). The investigators assessed patients at baseline and at 1 and 3 months of immunosuppressive therapy.

The analysis included 55 patients who had active SLE; mean age was 34 years (SD 13 years), 93% were women, 93% received intravenous methylprednisolone as immunosuppressive therapy, and 95% were seropositive for CMV.


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Of 42 evaluable patients at baseline, 4/16 (25%) patients with clinically significant CMV infection were QF-positive and 8/26 (28.6%) patients with clinically significant CMV were QF-negative (P =.69). Of 35 evaluable patients after 1 month of immunosuppressive therapy, 2/17 (11.8%) patients with clinically significant CMV infection were QF-positive and 8/18 (44.4%) patients with clinically significant CMV infection were QF-negative (P =.03). However, among 19 patients whose full data were available before and after immunosuppressive therapy, there was no significant trend in QF status for clinically significant CMV infection (P =.63).

Although  pre-immunosuppression QF status did not predict CMV infection in this patient population, a Cox proportional hazard model showed that 1 month after immunosuppression, QF-negative status in patients with active SLE was significantly associated with clinically significant CMV infection in both univariate (hazard ratio [HR] 4.89; 95% CI, 1.06-22.74, P =.04) and multivariate (adjusted HR 4.97; 95% CI, 1.07-23.10, P =.04) analysis.

Neuropsychiatric symptoms of SLE had a marginal association with CMV infection (HR 2.73; 95% CI, 0.84-8.88, P =.09). Other factors such as age, sex, SLE Disease Activity Index 2000 (SLEDAI-2K) score, immunosuppressant type, and lymphopenia were not associated with clinically significant CMV infection.

Study limitations include the small sample size, missing QF data for some patients, and the lack of an established cutoff for CMV DNA loads to initiate pre-emptive immunosuppressive therapy.

The study authors wrote that their results “increase awareness of CMV prevention in patients with autoimmune diseases scheduled to receive aggressive doses of immunosuppressants.” Anti-CMV IgG traditionally predicts CMV infection risk, yet several patients in this study who were CMV seropositive had QF-negative status. The QF assay therefore “could identify individuals at higher risk of infection,” the study authors added.

Reference

Bruminhent J, Autto S, Rotjanapan P, et al; and the Ramathibodi Clinical and Immunological Disease (RCID) Study Group. A prospective study of cytomegalovirus-specific cell-mediated immune monitoring and cytomegalovirus infection in patients with active systemic lupus erythematosus receiving immunosuppressants. Open Forum Infect Dis. Published online May 16, 2021. doi:10.1093/ofid/ofab248