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Systemic immune responses in patients with early localized or early disseminated Borrelia afzelii lyme borreliosis.

ABSTRACT:

Introduction

The role of host immune responses in the pathogenesis of borrelial dissemination in early Lyme borreliosis (LB) in the form of multiple erythema migrans (MEM) or LB-associated symptoms is incompletely understood.

Methods

In this study, fifteen cytokine or chemokine levels, representative of innate, Th1, and Th17 immune responses, were assessed using a bead-based Luminex multiplex assay in acute sera from 76 adult patients with skin culture-positive Borrelia afzelii solitary erythema migrans (SEM) and 58 patients with MEM at a single-center university hospital. Differences between the groups were tested by modeling each cytokine or chemokine concentration by means of left-censored regression using the classic Tobit model.

Results

Mean serum cytokine or chemokine levels were low. When taking into account the proportion of patients with cytokine or chemokine concentrations below the lowest detectable limit, only levels of CXCL10 (p = .03) and CCL19 (p = .02), representatives of the Th1 immune response, differed between patients with SEM and those with MEM; however, the differences did not reach statistical significance when adjusted for multiple comparisons. In addition, we did not find differences in systemic inflammatory responses when comparing patients with and those without LB-associated constitutional symptoms.

Conclusion

No significant differences in systemic immune responses represented by selected cytokines or chemokines in serum samples of patients with EM infected with B. afzelii suggest that systemic mediators are not pivotal in the pathogenesis of dissemination of early infection in the form of MEM or LB-associated symptoms. Localized immune responses in the skin or other pathogenetic mechanisms may be more important in this regard.

SUBMITTER: Cerar Kisek T

PROVIDER: S-EPMC8127568 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ImportanceMultiple erythema migrans (MEM) has been suggested as a risk factor for unfavorable antibiotic treatment outcome compared with solitary erythema migrans (EM). However, no direct comparison of early Lyme borreliosis manifested as MEM with solitary EM has been undertaken.ObjectiveTo investigate the potential differences in clinical course and treatment outcome between MEM and solitary EM.Design, setting, and participantsThis prospective cohort study was conducted from June 1, 2010, to October 31, 2015, at the University Medical Center Ljubljana, Slovenia. Data were analyzed from June 1, 2017, to January 3, 2018. Of the 778 consecutive adult patients with early Lyme borreliosis evaluated, 200 patients with MEM and 403 patients with solitary EM were enrolled. Patients were asked to refer a family member or a friend of similar age (±5 years) without a history of Lyme borreliosis to serve as a control participant. Clinical course and posttreatment outcome of MEM were compared with those of solitary EM. Outcome was assessed at 14 days and at 2, 6, and 12 months after enrollment. At each visit, patients completed a written questionnaire about their symptoms; controls completed the same questionnaire. Nonspecific symptoms reported by patients and controls without a history of Lyme borreliosis were compared.Main outcomes and measuresThe proportion of patients with incomplete response at 12 months after enrollment and the associated 2-sided 95% CI for the difference between MEM and solitary EM were estimated using the normal approximation with continuity correction.ResultsA total of 200 patients with MEM and 403 patients with solitary EM were included. Among the 200 patients with MEM, 94 (47.0%) were males and 106 (53.0%) were females, with a median (interquartile range [IQR]) age of 47 (35-58) years. Among the 403 patients with solitary EM, 182 (45.2%) were males and 221 (54.8%) were females, with a median (IQR) age of 55 (42-62) years. Patients with MEM reported Lyme borreliosis-associated constitutional symptoms at enrollment more often than those with solitary EM (93 [46.5%]; 95% CI, 39.4-53.7 vs 96 [23.8%]; 95% CI, 19.7-28.3; P?<?.001). During the initial 6 months after treatment, the proportion of patients with incomplete response was higher in the MEM group than in the solitary EM group (14 days: 62 of 193 [32.1%] vs 72 of 391 [18.4%]; P?<?.001; 2 months: 38 of 193 [19.7%] vs 55 of 394 [14.0%]; P?=?.28; 6 months: 29 of 182 [15.9%] vs 31 of 359 [8.6%]; P?=?.02). However, at the 12-month visit, the outcome was comparable: 10 of 170 (5.9%) patients with MEM vs 20 of 308 (6.5%) patients with solitary EM showed incomplete response (-0.6; 95% CI, -5.5 to 4.3; P?=?.95). The frequency of nonspecific symptoms in patients was similar to that in controls.Conclusions and relevanceThe long-term outcome at 12 months after treatment was comparable, regardless of dissemination. Follow-up of at least 12 months after treatment is thus recommended for future studies that investigate post-Lyme borreliosis symptoms.

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