Elevated levels of IL-23 in a subset of patients with post-lyme disease symptoms following erythema migrans.
BACKGROUND
The causes of post-Lyme disease symptoms are unclear. Herein, we investigated whether specific immune responses were correlated with such symptoms.


METHODS
The levels of 23 cytokines and chemokines, representative of innate and adaptive immune responses, were assessed in sera from 86 antibiotic-treated European patients with erythema migrans, 45 with post-Lyme symptoms and 41 without symptoms, who were evaluated prior to treatment and 2, 6, and 12 months thereafter.


RESULTS
At study entry, significant differences between groups were observed for the type 1 helper T cell (TH1)-associated chemokines CXCL9 and CXCL10, which were associated with negative Borrelia cultures, and the type 17 helper T cell (TH17)-associated cytokine interleukin 23 (IL-23), which was associated with positive cultures and the development of post-Lyme symptoms (P ≤ .02). Moreover, of the 41 patients with detectable IL-23 levels, 25 (61%) developed post-Lyme symptoms, and all 7 with IL-23 levels ≥ 230 ng/mL had such symptoms. Furthermore, antibody responses to the ECGF autoantigen were more common in patients with post-Lyme symptoms (P = .07) and were correlated directly with IL-23 levels (P = .02). Despite the presence of post-Lyme symptoms, all posttreatment culture results were negative, antiborrelial antibody responses declined, and there were no objective signs of disseminated disease, suggesting that spirochetal eradication had occurred with treatment in all patients.


CONCLUSIONS
High TH1-associated responses correlated with more effective immune-mediated spirochetal killing, whereas high TH17-associated immune responses, often accompanied by autoantibodies, correlated with post-Lyme symptoms, providing a new paradigm for the study of postinfectious symptoms in a subset of patients with Lyme disease.
Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital and Harvard Medical School, Boston.
Klemen
K
Strle
Daša
D
Stupica
Elise E
EE
Drouin
Allen C
AC
Steere
Franc
F
Strle
D000293:Adolescent; D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood; D015787:Erythema Chronicum Migrans / Q000276:immunology*; D005060:Europe; D005260:Female; D006801:Humans; D053759:Interleukin-23 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology; D013939:Thymidine Phosphorylase / Q000276:immunology; D055815:Young Adult
D001323:Autoantibodies; D053759:Interleukin-23; C543750:TYMP protein, human; D013939:Thymidine Phosphorylase
IL-23; Lyme disease; TH17; inflammation; post–Lyme disease symptoms