Sex-Based Differences in the Immune Response in Lyme Disease Over Time

Background:

Lyme disease, caused by the spirochete Borrelia burgdorferi, is an inflammatory illness with early and late manifestations. Chemokines such as CCL19 are involved in directing the immunologic response in Lyme disease. Sex-based differences in immunologic response have been described in other infectious diseases. Despite its increasing prevalence, little research has been done regarding sex-based differences in the immune response or clinical symptoms in early Lyme disease.

Methods:

Eighty-six participants (45 men and 41 women) with clinically diagnosed erythema migrans were enrolled in a prospective cohort study prior to standard antibiotic treatment and followed at five time points over one year. At every visit, a physical exam, health interview and blood draw were performed. Serum immune proteins were measured using a Luminex-based system. Data were analyzed using a statistical package for microarray analysis and SAS statistical software.  Patient values were also compared to values from 26 matched controls.

Results:
Male and female non-Lyme controls did not differ significantly in level of the chemokine CCL19 (p=0.52). Female Lyme patients had a higher CCL19 level than male patients at the pre-treatment visit (Figure 1, p=0.003). A subset of largely female patients had elevated CCL19 values at one or more of the subsequent visits. This “tail” was not observed among non-Lyme controls of either sex. Using the third quartile (Q₃) as a cut-off, female Lyme patients were significantly more likely to fall above the Q₃ at the pre-treatment (p=0.001), 4-week (p=0.04), 3-month (p=0.007) and 6-month visits (p=0.02). Patients above the Q₃ were also more likely to report persistent symptoms at each of the post-treatment follow-up visits, up to 6-months (p= 0.01, p=0.02, p=0.02, p=0.04, respectively).

Conclusion:

These results suggest clear sex-based differences in initial and later CCL19 reactivity to early Lyme disease.  Post-treatment elevations of CCL19 may be a risk factor for development of persistent symptoms, which appear to be more common in women than men. Clinically relevant sex-based differences in the immune response to early Lyme disease merit future research and may call for different disease management and treatment approaches.