Detection of human antibody responses to tick-borne Neoehrlichia mikurensis

Tick-borne Neoehrlichia mikurensis is the cause of neoehrlichiosis, an infectious disease that features fever and vascular events. Compromised B-cell immunity is a risk factor for severe neoehrlichiosis, indicating the importance of antibodies in host defense. The development of serological assays has been hampered by the difficulty of culturing these intracellular bacteria. Here we present the first serological test for N. mikurensis, an ELISA for human IgM and IgG antibody responses to a P44/Msp2 protein of N. mikurensis. Serum or plasma from immunocompetent (n = 44) and immunosuppressed (n = 60) Swedish adults infected with N. mikurensis, with and without symptoms, were analyzed and compared with blood samples from non-infected immunocompetent individuals (n = 17). Sera from non-infected children (n = 23) and plasma from cord blood (n = 10) were also analyzed. Immunocompetent neoehrlichiosis adults had higher IgM and IgG antibody levels compared with immunosuppressed neoehrlichiosis patients treated with the B-cell suppressive agent rituximab. There were no significant differences in the IgM or IgG antibody levels between immunocompetent individuals with symptomatic versus asymptomatic N. mikurensis infection. Sera from healthy children contained high levels of IgM antibodies, despite no evidence of current infection with N. mikurensis nor previous exposure to tick bites as reflected by negative Borrelia serology. This IgM response was absent in cord blood plasma (n = 10), indicating it was not due to natural IgM antibodies. The high constitutional IgM antibody levels to N. mikurensis in children may explain why there have been no reports of pediatric neoehrlichiosis.