Toll-like receptor 2 (TLR2) polymorphisms are associated with reversal reaction in leprosy.
BACKGROUND
Leprosy is characterized by a spectrum of clinical manifestations that depend on the type of immune response against the pathogen. Patients may undergo immunological changes known as "reactional states" (reversal reaction and erythema nodosum leprosum) that result in major clinical deterioration. The goal of the present study was to assess the effect of Toll-like receptor 2 (TLR2) polymorphisms on susceptibility to and clinical presentation of leprosy.


METHODS
Three polymorphisms in TLR2 (597C-->T, 1350T-->C, and a microsatellite marker) were analyzed in 431 Ethiopian patients with leprosy and 187 control subjects. The polymorphism-associated risk of developing leprosy, lepromatous (vs. tuberculoid) leprosy, and leprosy reactions was assessed by multivariate logistic regression models.


RESULTS
The microsatellite and the 597C-->T polymorphisms both influenced susceptibility to reversal reaction. Although the 597T allele had a protective effect (odds ratio [OR], 0.34 [95% confidence interval {CI}, 0.17-0.68]; P= .002 under the dominant model), homozygosity for the 280-bp allelic length of the microsatellite strongly increased the risk of reversal reaction (OR, 5.83 [95% CI, 1.98-17.15]; P= .001 under the recessive model). These associations were consistent among 3 different ethnic groups.


CONCLUSIONS
These data suggest a significant role for TLR-2 in the occurrence of leprosy reversal reaction and provide new insights into the immunogenetics of the disease.
Bochud
Pierre-Yves
PY
Institute for Systems Biology, Seattle, WA 98103-8904, USA. pyb@systemsbiology.org
Hawn
Thomas R
TR
Siddiqui
M Ruby
MR
Saunderson
Paul
P
Britton
Sven
S
Abraham
Isaac
I
Argaw
Azeb Tadesse
AT
Janer
Marta
M
Zhao
Lue Ping
LP
Kaplan
Gilla
G
Aderem
Alan
A
D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005002:Ethiopia; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007918:Leprosy / Q000208:ethnology / Q000235:genetics* / Q000276:immunology* / Q000503:physiopathology; D015810:Linkage Disequilibrium; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D051195:Toll-Like Receptor 2 / Q000235:genetics*
D051195:Toll-Like Receptor 2