Although intensive studies have attempted to elucidate the genetic background of bronchial asthma (BA), one of the most common of the chronic inflammatory diseases in human populations, genetic factors associated with its pathogenesis are still not well understood. We surveyed 29 possible candidate genes for this disease for single nucleotide polymorphisms (SNPs), the most frequent type of genetic variation, in genomic DNAs from Japanese BA patients. We identified 33 SNPs, only four of which had been reported previously, among 14 of those genes. We also performed association studies using 585 BA patients and 343 normal controls for these SNPs. Of the 33 SNPs tested, 32 revealed no positive association with BA, but a T924C polymorphism in the thromboxane A2 receptor gene showed significant association (chi2=4.71, P=0.030), especially with respect to adult patients (chi2=6.20, P=0.013). Our results suggest that variants of the TBXA2R gene or some nearby gene(s) may play an important role in the pathogenesis of adult BA.

Asthma is a phenotypically heterogeneous disorder with many etiologic factors and clinical characteristics. T-bet, a Th1-specific transcription factor of T-box family, has been found to control interferon-gamma (IFN-gamma) expression in T cells. Mice lacking the T-bet gene (tbx21) demonstrate multiple physiological and inflammatory features reminiscent of human asthma. In order to examine whether polymorphisms in the candidate gene, TBX21, located on chromosome 17q21.32, are related to the risk of human asthma phenotypes, we have searched for genetic variations in the human TBX21 gene and identified 24 single nucleotide polymorphisms (SNPs), including five novel SNPs, by direct sequencing in Japanese subjects. Among asthma phenotypes, a promoter -1993T-->C SNP, which is in linkage disequilibrium with a synonymous coding 390A-->G SNP in exon 1, is significantly associated with a risk of aspirin-induced asthma (AIA; P = 0.004, P(c) = 0.016). This association has also been confirmed in additional independent samples of asthma with nasal polyposis (P = 0.008), regardless of aspirin hypersensitivity. Furthermore, our data indicate that the -1993T-->C substitution increases the affinity of a particular nuclear protein to the binding site of TBX21 covering the -1993 position, resulting in increased transcriptional activity of the TBX21 gene. Thus, in addition to the antigen-driven excess Th2 response, increased T-bet (and subsequent IFN-gamma) production in human airways of individuals with the -1993T-->C polymorphism could contribute to the development of certain asthma-related phenotypes, such as AIA.

This is the first proposal for diagnosis and classification of CD by the Japanese group. Further studies are required to validate whether they can distinguish CD from other inflammatory diseases and to determine their sensitivity and specificity.

The aim of this study was to investigate long-term prognosis and relapse of dermatomyositis complicated with interstitial pneumonia (DMIP) according to anti-aminoacyl tRNA synthetase (ARS) antibodies and anti-melanoma differentiation-associated gene 5 (MDA5) antibody. This retrospective study comprised 36 patients with DMIP who were divided into the anti-ARS antibody-positive group (ARS+) (n = 12), anti MDA5 antibody-positive group (MDA5+) (n = 11), double-negative group (ARS-/MDA5-) (n = 11), and double-positive group (ARS+/MDA5+) (n = 1). Clinical features, treatment, prognoses, and relapses during the 2 years after initiation of treatment were compared between three groups excluding ARS+/MDA5+ group. Although short-term (24-week) mortality in MDA+ was higher than that in ARS+ or ARS-/MDA5- (P = 0.004), there was no difference in long-term (2-year) mortality between the three groups. Relapse rate in ARS+ was higher than that in MDA5+ and ARS-/MDA5- during the 2 years after initiation of treatment (P = 0.044). There was no difference in serum KL-6 levels at the initiation of treatment between ARS+ and MDA5+, but serum ferritin levels in MDA5+ were significantly higher than those in ARS+ (P = 0.406, 0.042, respectively). Serum KL-6 and ferritin levels at 2 years after initiation of treatment in ARS+ were significantly higher than those in MDA5+ (P = 0.008, 0.034, respectively). We found that in MDA5+ DMIP, acute alveolar inflammation caused a poor prognosis early in the disease course, and in ARS+ DMIP, chronic injury to the alveolar epithelial cells or basement membrane caused long-term recurrence.

Background An increased incidence of pneumococcal infection triggered by influenza infection has been reported. Objective To examine the effectiveness of the additive inoculation of influenza vaccine (I-V) and 23-valent pneumococcal vaccine (P-V)