Susceptibility to tuberculosis is associated with TLR1 polymorphisms resulting in a lack of TLR1 cell surface expression.

Human TLR1 plays an important role in host defense against Mycobacterium tuberculosis. Our aim was to analyze the association of the loss of TLR1 surface expression and TLR1 SNPs with susceptibility to TB. TLR1neg and TLR1pos cells from healthy individuals were identified by flow cytometry and compared by sequencing. TLR1 expression was measured using quantitative real-time PCR and immunoblotting. TLR1 SNP analyses of healthy individuals and TB patients from EU-C and Ghana were performed, and association of the TLR1 genotypes with increased risk of developing TB was statistically evaluated. Lack of TLR1 surface expression accompanied by impaired function was strongly associated with TLR1 SNP G743A. Genotyping of EU-C controls and TB patients revealed an association of TLR1 743A/1805G alleles [OR 2.37 (95% CI 1.13, 4.93), P=0.0219; OR 2.74 (95% CI 1.26, 6.05), P=0.0059] as well as TLR1neg 743AA/1805GG versus TLR1pos genotypes 743AG/1805TG [OR 4.98 (95% CI 1.64, 15.15), P=0.0034; OR 5.70 (95% CI 1.69, 20.35), P=0.0015] and 743AG + GG/1805TG + TT [OR 3.54 (95% CI 1.29, 9.90), P=0.0086; OR 4.17 (95% CI 1.52, 11.67), P=0.0025] with increased susceptibility to TB. No association of G743A with TB was found in Ghana as a result of a low frequency of genotype 743AA. Our data gain new insights in the role of TLR1 in M. tuberculosis defense and provide the first evidence that TLR1 variants are associated with susceptibility to TB in a low-incidence country.

Assessment of lymph node tuberculosis in northern Germany: a clinical review.

AIM OF STUDY: To evaluate patient profiles, diagnostic approaches, and treatment strategies in patients with lymph node tuberculosis. METHODS: Demographic data, diagnostic findings, and therapies were retrospectively analyzed in 60 patients with lymph node tuberculosis who were hospitalized between 1992 and 1999. RESULTS: Thirty percent (n = 18) of patients were natives, and 70% were immigrants (n = 42). The cervical lymph nodes were most frequently involved (63.3%), followed by the mediastinal lymph nodes (26.7%) and the axillary lymph nodes (8.3%). All patients (except one patient who was HIV-positive) showed a positive response to tuberculin skin testing. Lymph node excision and fine-needle aspiration (FNA) were similarly effective in obtaining sufficient material for histologic and microbiological analysis. Mycobacterium tuberculosis was identified in 43.3% of patients by microbiological testing, and culture methods showed the highest sensitivity. Despite standard treatment, the initial enlargement of the lymph nodes occurred in 20% of patients and local complications occurred in 10%. CONCLUSION: Lymph node tuberculosis is still an important issue in developed countries and has to be considered in differential diagnosis. The best approach appears to be a combination of skin testing and FNA. Negative results in the identification of M tuberculosis do not exclude the diagnosis of lymph node tuberculosis.