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Borrelia burgdorferi is a bacterial spirochete that can cause Lyme disease (LD) after infecting a susceptible host. Immune responses to the bacteria are highly variable and host specific. The murine substrain, C3H/HeJ, is a frequently utilized model for LD. Interestingly, we observed dermatitis with flaky lesions of the tail skin on C3H/HeJ after a year of infection with B. burgdorferi. Female C3H/HeJ mice aged 6-8 weeks, 1 year, or 2 years were infected intraperitoneally with 105B. burgdorferi spirochetes. Mouse tails were evaluated by gross examination and histology either 2 months or 24 months post-infection. Dermatitis worsened over the course of untreated infection, with ulceration, hemorrhaging, flaking, hair loss, and dark lesions as well as spongiosis and acanthosis. These features of atopic dermatitis were present in infected mice after 1 year of age. This relationship among LD, atopic dermatitis, and host age seen in the C3H/HeJ mouse model is consistent with a large pool of human epidemiological data (342,499 individuals) from Finland. We identified 5,248 individuals with LD and 17,233 with atopic dermatitis in FinnGen. Retrospective analysis shows LD is associated with atopic dermatitis (OR = 1.91 [1.68 −2.37], P < 2e−16). Repeat visits for LD complications (3 or more visits versus 1 visit) were associated with atopic dermatitis (OR = 2.19 [1.35-3.55], P = 0.0014) and risk of developing atopic dermatitis over time (HR=2.26 [1.54-3.95], P = 0.0017). Data from mice and humans reveal a novel relationship among LD, age, and atopic dermatitis. Through defined pathological scoring, we demonstrate that the onset of murine Lyme disease associated atopic dermatitis is exacerbated by increased host age at time of B. burgdorferi infection. In humans, a diagnosis of Lyme disease in FinnGen was associated with atopic dermatitis and further research is warranted to establish causation.ETHICS APPROVAL/CONSENT TO PARTICIPATEAnimal studies were performed at the Stanford School of Medicine Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC) accredited Rodent Animal Facility (Palo Alto, CA). All procedures and care guidelines were approved by the Stanford University Administrative Panel on Laboratory Animal Care (Protocol #30109).Patients and control subjects in FinnGen provided informed consent for biobank research, based on the Finnish Biobank Act. Alternatively, separate research cohorts, collected prior the Finnish Biobank Act came into effect (in September 2013) and start of FinnGen (August 2017), were collected based on study-specific consents and later transferred to the Finnish biobanks after approval by Fimea (Finnish Medicines Agency), the National Supervisory Authority for Welfare and Health. Recruitment protocols followed the biobank protocols approved by Fimea. The Coordinating Ethics Committee of the Hospital District of Helsinki and Uusimaa (HUS) statement number for the FinnGen study is Nr HUS/990/2017. |
