Latent Neoehrlichia mikurensis Infections May Be Reactivated in Patients With B-Cell Lymphomas Treated With Rituximab

The intracellular, tick-borne bacterium Neoehrlichia (N.) mikurensis can cause neoehrlichiosis in patients with compromised B-cell defences, while immunocompetent individuals are frequently healthy carriers of the infection. We hypothesised that N. mikurensis induces latent infections that reactivate when B-cell immunity is compromised. We tested this hypothesis by determining the incidence of N. mikurensis reactivation in 97 patients with B-cell lymphomas who were treated with anti-CD20 antibody therapy (rituximab) and evaluating the presence of N. mikurensis-specific T cells in latently infected individuals. Four patients (4%) reactivated N. mikurensis infection and four patients (4%) had asymptomatic infection before the initiation of B-cell suppression. All eight patients who were infected with N. mikurensis had N. mikurensis-specific, perforin-expressing Th1 and CD8+ T-cell populations with up-regulation of CXCL10 and IFN-γ, in contrast to the noninfected lymphoma patients who lacked these T-cell subsets. The infected lymphoma patients also had expanded γδ T-cell populations. This study supports the notion of latent, reactivatable N. mikurensis infections.