Toll-Like Receptor 2 (TLR2) Polymorphisms Are Associated with Reversal Reaction in Leprosy

• Published in: The Journal of infectious diseases Vol. 197; no. 2; pp. 253 - 261
• Main Authors: Bochud, Pierre-Yves, Hawn, Thomas R., Siddiqui, M. Ruby, Saunderson, Paul, Britton, Sven, Abraham, Isaac, Argaw, Azeb Tadesse, Janer, Marta, Zhao, Lue Ping, Kaplan, Gilla, Aderem, Alan
• Format: Journal Article
• Language: English
• Published: Chicago, IL The University of Chicago Press 15.01.2008; University of Chicago Press
• Subjects: Adolescent; Adult; Bacteria; Bacterial diseases; Biological and medical sciences; Case-Control Studies; Child; Child, Preschool; Ethiopia; Ethnic groups; Ethnicity; Female; Genetic Predisposition to Disease; Haplotypes; Human bacterial diseases; Humans; Infant; Infant, Newborn; Infectious diseases; Leprosy; Leprosy - ethnology; Leprosy - genetics; Leprosy - immunology; Leprosy - physiopathology; Linkage Disequilibrium; Male; Medical genetics; Medical sciences; Microbial genetics; Microsatellite Repeats; Microsatellites; Middle Aged; Polymorphism, Genetic; Polymorphism, Single Nucleotide; rev genes; Toll like receptors; Toll-Like Receptor 2 - genetics; Tropical bacterial diseases; Ethiopia; Infection; Skin disease; Bacteriosis; Leprosy; Toll like receptor; Mycobacterial infection; Leprosy reaction; Polymorphism
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/524688

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.