TY - JOUR KW - Adolescent KW - Adult KW - Case-Control Studies KW - Child KW - Child, Preschool KW - Ethiopia KW - Female KW - Genetic Predisposition to Disease KW - Haplotypes KW - Humans KW - Infant KW - Infant, Newborn KW - leprosy KW - Linkage Disequilibrium KW - Male KW - Microsatellite Repeats KW - Middle Aged KW - Polymorphism, Genetic KW - Polymorphism, Single Nucleotide KW - Toll-Like Receptor 2 AU - Bochud P AU - Hawn TR AU - Siddiqui RM AU - Saunderson P AU - Britton S AU - Abraham I AU - Argaw AT AU - Janer M AU - Zhao LP AU - Kaplan G AU - Aderem A AB -

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.

BT - The Journal of infectious diseases C1 - http://www.ncbi.nlm.nih.gov/pubmed/18177245?dopt=Abstract DA - 2008 Jan 15 DO - 10.1086/524688 IS - 2 J2 - J. Infect. Dis. LA - eng N2 -

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.

PY - 2008 SP - 253 EP - 61 T2 - The Journal of infectious diseases TI - Toll-like receptor 2 (TLR2) polymorphisms are associated with reversal reaction in leprosy. UR - http://jid.oxfordjournals.org/content/197/2/253.full.pdf+html?sid=64d8458a-d31d-4e85-a05a-5e5d1a69b0d4 VL - 197 SN - 0022-1899 ER -