Nontuberculous mycobacterial cervicofacial lymphadenitis in children from the multicenter, randomized, controlled trial in The Netherlands: relevance of polymorphisms in candidate host immunity genes.
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.
Haverkamp
Margje H
MH
Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands. M.H.Haverkamp@lumc.nl
Lindeboom
Jerome A
JA
de Visser
Adriëtte W
AW
Kremer
Dennis
D
Kuijpers
Taco W
TW
van de Vosse
Esther
E
van Dissel
Jaap T
JT
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005787:Gene Frequency; D005820:Genetic Testing; D006579:Heterozygote; D006801:Humans; D007223:Infant; D016753:Interleukin-10 / Q000235:genetics*; D053583:Interleukin-1beta / Q000235:genetics*; D008199:Lymphadenitis / Q000453:epidemiology / Q000235:genetics* / Q000382:microbiology*; D009154:Mutation; D009164:Mycobacterium Infections / Q000453:epidemiology*; D009426:Netherlands / Q000453:epidemiology; D010518:Periodontitis / Q000235:genetics; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011159:Population Surveillance; D011446:Prospective Studies; D017471:Receptors, Interferon / Q000235:genetics; D014078:Tooth Eruption; D000096743:Interferon gamma Receptor
D016753:Interleukin-10; D053583:Interleukin-1beta; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor; C508609:IL10 protein, human; C508585:IL1B protein, human