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

ABSTRACT 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.