A comprehensive genetic map of cytokine responses in Lyme borreliosis

Javier Botey-Bataller; Hedwig D. Vrijmoeth; Jeanine Ursinus; Bart-Jan Kullberg; Cees C. van den Wijngaard; Hadewych ter Hofstede; Ahmed Alaswad; Manoj K. Gupta; Lennart M. Roesner; Jochen Huehn; Thomas Werfel; Thomas F. Schulz; Cheng-Jian Xu; Mihai G. Netea; Joppe W. Hovius; Leo A. B. Joosten; Yang Li

doi:10.1038/s41467-024-47505-z

A comprehensive genetic map of cytokine responses in Lyme borreliosis

Javier Botey-Bataller, Hedwig D. Vrijmoeth, Jeanine Ursinus, Bart-Jan Kullberg, Cees C. van den Wijngaard, Hadewych ter Hofstede, Ahmed Alaswad, Manoj K. Gupta, Lennart M. Roesner, Jochen Huehn, Thomas Werfel, Thomas F. Schulz, Cheng-Jian Xu, Mihai G. Netea, Joppe W. Hovius, Leo A. B. Joosten, Yang Li

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

The incidence of Lyme borreliosis has risen, accompanied by persistent symptoms. The innate immune system and related cytokines are crucial in the host response and symptom development. We characterized cytokine production capacity before and after antibiotic treatment in 1,060 Lyme borreliosis patients. We observed a negative correlation between antibody production and IL-10 responses, as well as increased IL-1Ra responses in patients with disseminated disease. Genome-wide mapping the cytokine production allowed us to identify 34 cytokine quantitative trait loci (cQTLs), with 31 novel ones. We pinpointed the causal variant at the TLR1-6-10 locus and validated the regulation of IL-1Ra responses at transcritpome level using an independent cohort. We found that cQTLs contribute to Lyme borreliosis susceptibility and are relevant to other immune-mediated diseases. Our findings improve the understanding of cytokine responses in Lyme borreliosis and provide a genetic map of immune function as an expanded resource.

Original language	English
Article number	3795
Journal	Nature communications
Volume	15
Issue number	1
DOIs	https://doi.org/10.1038/s41467-024-47505-z
Publication status	Published - 1 Dec 2024

Access to Document

10.1038/s41467-024-47505-z

Cite this

Botey-Bataller, J., Vrijmoeth, H. D., Ursinus, J., Kullberg, B.-J., van den Wijngaard, C. C., ter Hofstede, H., Alaswad, A., Gupta, M. K., Roesner, L. M., Huehn, J., Werfel, T., Schulz, T. F., Xu, C.-J., Netea, M. G., Hovius, J. W., Joosten, L. A. B., & Li, Y. (2024). A comprehensive genetic map of cytokine responses in Lyme borreliosis. Nature communications, 15(1), Article 3795. https://doi.org/10.1038/s41467-024-47505-z

@article{6fc64230d56c49f38e519ff2b4390986,

title = "A comprehensive genetic map of cytokine responses in Lyme borreliosis",

abstract = "The incidence of Lyme borreliosis has risen, accompanied by persistent symptoms. The innate immune system and related cytokines are crucial in the host response and symptom development. We characterized cytokine production capacity before and after antibiotic treatment in 1,060 Lyme borreliosis patients. We observed a negative correlation between antibody production and IL-10 responses, as well as increased IL-1Ra responses in patients with disseminated disease. Genome-wide mapping the cytokine production allowed us to identify 34 cytokine quantitative trait loci (cQTLs), with 31 novel ones. We pinpointed the causal variant at the TLR1-6-10 locus and validated the regulation of IL-1Ra responses at transcritpome level using an independent cohort. We found that cQTLs contribute to Lyme borreliosis susceptibility and are relevant to other immune-mediated diseases. Our findings improve the understanding of cytokine responses in Lyme borreliosis and provide a genetic map of immune function as an expanded resource.",

author = "Javier Botey-Bataller and Vrijmoeth, {Hedwig D.} and Jeanine Ursinus and Bart-Jan Kullberg and {van den Wijngaard}, {Cees C.} and {ter Hofstede}, Hadewych and Ahmed Alaswad and Gupta, {Manoj K.} and Roesner, {Lennart M.} and Jochen Huehn and Thomas Werfel and Schulz, {Thomas F.} and Cheng-Jian Xu and Netea, {Mihai G.} and Hovius, {Joppe W.} and Joosten, {Leo A. B.} and Yang Li",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2024.",

year = "2024",

month = dec,

day = "1",

doi = "10.1038/s41467-024-47505-z",

language = "English",

volume = "15",

journal = "Nature communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

number = "1",

}

Botey-Bataller, J, Vrijmoeth, HD, Ursinus, J, Kullberg, B-J, van den Wijngaard, CC, ter Hofstede, H, Alaswad, A, Gupta, MK, Roesner, LM, Huehn, J, Werfel, T, Schulz, TF, Xu, C-J, Netea, MG, Hovius, JW, Joosten, LAB & Li, Y 2024, 'A comprehensive genetic map of cytokine responses in Lyme borreliosis', Nature communications, vol. 15, no. 1, 3795. https://doi.org/10.1038/s41467-024-47505-z

TY - JOUR

T1 - A comprehensive genetic map of cytokine responses in Lyme borreliosis

AU - Botey-Bataller, Javier

AU - Vrijmoeth, Hedwig D.

AU - Ursinus, Jeanine

AU - Kullberg, Bart-Jan

AU - van den Wijngaard, Cees C.

AU - ter Hofstede, Hadewych

AU - Alaswad, Ahmed

AU - Gupta, Manoj K.

AU - Roesner, Lennart M.

AU - Huehn, Jochen

AU - Werfel, Thomas

AU - Schulz, Thomas F.

AU - Xu, Cheng-Jian

AU - Netea, Mihai G.

AU - Hovius, Joppe W.

AU - Joosten, Leo A. B.

AU - Li, Yang

PY - 2024/12/1

Y1 - 2024/12/1

N2 - The incidence of Lyme borreliosis has risen, accompanied by persistent symptoms. The innate immune system and related cytokines are crucial in the host response and symptom development. We characterized cytokine production capacity before and after antibiotic treatment in 1,060 Lyme borreliosis patients. We observed a negative correlation between antibody production and IL-10 responses, as well as increased IL-1Ra responses in patients with disseminated disease. Genome-wide mapping the cytokine production allowed us to identify 34 cytokine quantitative trait loci (cQTLs), with 31 novel ones. We pinpointed the causal variant at the TLR1-6-10 locus and validated the regulation of IL-1Ra responses at transcritpome level using an independent cohort. We found that cQTLs contribute to Lyme borreliosis susceptibility and are relevant to other immune-mediated diseases. Our findings improve the understanding of cytokine responses in Lyme borreliosis and provide a genetic map of immune function as an expanded resource.

AB - The incidence of Lyme borreliosis has risen, accompanied by persistent symptoms. The innate immune system and related cytokines are crucial in the host response and symptom development. We characterized cytokine production capacity before and after antibiotic treatment in 1,060 Lyme borreliosis patients. We observed a negative correlation between antibody production and IL-10 responses, as well as increased IL-1Ra responses in patients with disseminated disease. Genome-wide mapping the cytokine production allowed us to identify 34 cytokine quantitative trait loci (cQTLs), with 31 novel ones. We pinpointed the causal variant at the TLR1-6-10 locus and validated the regulation of IL-1Ra responses at transcritpome level using an independent cohort. We found that cQTLs contribute to Lyme borreliosis susceptibility and are relevant to other immune-mediated diseases. Our findings improve the understanding of cytokine responses in Lyme borreliosis and provide a genetic map of immune function as an expanded resource.

UR - http://www.scopus.com/inward/record.url?scp=85192222937&partnerID=8YFLogxK

U2 - 10.1038/s41467-024-47505-z

DO - 10.1038/s41467-024-47505-z

M3 - Article

C2 - 38714679

SN - 2041-1723

VL - 15

JO - Nature communications

JF - Nature communications

IS - 1

M1 - 3795

ER -

A comprehensive genetic map of cytokine responses in Lyme borreliosis

Abstract

Access to Document

Other files and links

Cite this