Nontuberculous mycobacterial cervicofacial lymphadenitis in children from the multicenter, randomized, controlled trial in The Netherlands: Relevance of polymorphisms in candidate host immunity genes

Haverkamp, Margje H.; Lindeboom, Jerome A.; de Visser, Adriëtte W.; Kremer, Dennis; Kuijpers, Taco W.; van de Vosse, Esther; van Dissel, Jaap T.

doi:10.1016/j.ijporl.2010.03.031

« Previous Next »International Journal of Pediatric Otorhinolaryngology
Volume 74, Issue 7 , Pages 752-754, July 2010

Nontuberculous mycobacterial cervicofacial lymphadenitis in children from the multicenter, randomized, controlled trial in The Netherlands: Relevance of polymorphisms in candidate host immunity genes

Margje H. Haverkamp
- Department of Infectious Diseases, Leiden University Medical Center, Albinusdreef 2, 2300 RC Leiden, The Netherlands
- Corresponding author. Tel.: +31 71 5262613; fax: +31 71 5266758.
Jerome A. Lindeboom
- Department of Oral and Maxillofacial Surgery, Academic Medical Center and Academic Center for Dentistry, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
Adriëtte W. de Visser
- Department of Infectious Diseases, Leiden University Medical Center, Albinusdreef 2, 2300 RC Leiden, The Netherlands
Dennis Kremer
- Department of Molecular Epidemiology, Leiden University Medical Center, Albinusdreef 2, 2300 RC Leiden, The Netherlands
Taco W. Kuijpers
- Emma Kinderziekenhuis AMC (EKZ), University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
Esther van de Vosse
- Department of Infectious Diseases, Leiden University Medical Center, Albinusdreef 2, 2300 RC Leiden, The Netherlands
Jaap T. van Dissel
- Department of Infectious Diseases, Leiden University Medical Center, Albinusdreef 2, 2300 RC Leiden, The Netherlands

Received 27 January 2010; accepted 16 March 2010.

Abstract

Objective

The annual incidence of nontuberculous mycobacterial (NTM) cervicofacial lymphadenitis in otherwise healthy children is unexpectedly high (8 per million). It mostly arises as localized cervicofacial lymphadenitis. Previous research has suggested environmental risk factors for oral exposure to NTM and a temporal association with eruption of teeth. We studied 22 polymorphisms in relevant candidate genes, some related to periodontitis, in children with NTM lymphadenitis. We also tested for the most common mutation in IFNGR1.

Methods

We analyzed DNA from 81 Dutch children with NTM from a nationwide surveillance study and 215 community controls for 22 polymorphisms in CD209, IL1B, IL8, IL10, IL12B, IL12RB1, IL18, PTX3, TLR4, TNF, VDR and SLC11A1 by MassArray platform (Sequenom) and CONTING. We screened for 818del4 in IFNGR1 by PCR and VspI restriction enzyme cleavage.

Results

We found a positive association between NTM lymphadenitis and +3953TT in IL1B (OR 2.9; 95%-CI: 1.2–7.2). Furthermore, our results showed that −592C/A heterozygosity in IL10 is linked to protection from disease (OR 0.54; 95%-CI: 0.3–0.95), but that other polymorphisms were unrelated to localized NTM disease. However, these associations were not robust to Bonferroni's correction for multiple testing. None of the children carried the IFNGR1 818del4 mutation.

Conclusions

Dominance of environmental factors over genetic ones and insufficient sample size might explain the fragility of this study's results. Nevertheless, the association between NTM lymphadenitis and 3953C>T, a polymorphism previously linked to periodontitis, supports our hypothesis that oral exposure to mycobacteria during eruption of teeth plays a role in the etiology of cervical NTM lymphadenitis.

Keywords: Nontuberculous mycobacteria, Single nucleotide polymorphism, Cervicofacial lymphadenitis, Periodontitis