中島 陽一

Background: The prevalence of asthma in industrialized countries has been increasing dramatically and asthma is now the most common chronic disease of children in the United States. The rapidity of the increase strongly suggests that changes in environmental exposures are the likely cause of this epidemic. Further, the early onset of allergic manifestations suggests that these exposures may act on the prenatal development of the immune system. We have focused on the potential effects of bisphenol A (BPA), a chemical pollutant with one of the largest productions, on the development of childhood asthma. We have reported that perinatal BPA exposure promotes the development of allergic asthma in a mouse model. The current study was designed to identify a critical period of BPA exposure and to begin elucidating the mechanisms for this susceptibility. Methods: Female BALB/c mice received 10 micro g/ml BPA in their drinking water from one week before pregnancy until the end of the study. Some of the pups were transferred in the first 48 h of life from their BPAloaded mother to an unexposed mother, or vice versa. Half of the pups were sensitized with a low dose of the experimental allergen ovalbumin (OVA), the rest received PBS as an unsensitized controls. On day 22, the pups were challenged by inhalations of ovalbumin or PBS followed by quantification of eosinophils in and hyperreactivity of their airways, major indicators of experimental asthma in this classical mouse model. Hepatic expression of two isoforms of UDP-glucuronosyltransferase (Ugt) was quantified by quantitative RT-PCR at various ages. Results: Pups exposed to BPA in utero and through breast milk, or in utero only, displayed an asthma phenotype in response to their "suboptimal" allergic sensitization, whereas, pups only exposed to BPA postnatally from breast milk, did not. The expression of Ugt2b1, an isoform related to BPA clearance in rats, was not detectable in mouse fetuses and newborn pups, but increased by day 5 and approached adult levels by day 25. Conclusions: Prenatal exposures that produce environmentally relevant burdens of BPA, followed by postnatal allergic sensitization and challenges, promote the development of experimental allergic asthma. Delayed expression of BPA-metabolizing enzymes may explain, at least in part, the enhanced fetal susceptibility to this common environmental contaminant.

オレンジアレルギー患者3例を経験したので、アレルゲンの解析結果を含めて報告した。症例1は22歳女で、10歳頃からオレンジ摂取後に咽頭のそう痒感・違和感が出現するようになった。症例2は17歳男で、3歳時に喘息で入院していたときオレンジ摂取によって口周囲に発赤・発疹が出現した。学童期から花粉症がひどくなり、オレンジを食べるたびに咽頭のそう痒感・イガイガ感が出現するようになった。症例3は31歳女で、学童期からスイカ・メロン摂取による咽頭そう痒感があり、17〜18歳頃からオレンジでも発症するようになった。3例とも全身症状は認めなかった。アレルゲン解析の結果、各種タンパクバンドのうち2例以上が反応したバンドは、13kDa、18kDa、23kDa、37kDa、53kDa付近にあった。2例は花粉症があり、他の1例もスギ花粉に感作されていたことから、スギ花粉との関連について検討した。その結果、オレンジ13kDa・75kDaタンパクに対するIgE結合がスギ花粉の添加によって抑制された。

Many immunedeficiency syndromes are associated with autoimmune disorders. We here report on a girl with a systemic lupus erythematosus-like disease who suffered from both hyperimmunoglobulin M syndrome (HIGMS) and Clq deficiency. Despite severe central nervous system-lupus like disease, probably due to Clq deficiency, kidney function was relatively spared. IgM autoantibody might play a protective role against lupus-glomerulonephritis.

Familial Mediterranean fever (FMF) is an autosomal recessive disorder characterized by recurrent and self-limited fever attacks and serositis/arthritis. The M694V, M694I, M680I, V726A, and E148Q mutations in MEFV, the gene responsible for FMF, account for most FMF cases in Mediterranean populations. In Japan, M694I and E148Q are most frequently detected; M694V, M680I, and V726A have not been identified so far. We report the first case of FMF associated with M680I in Japan.

我々は、鶏卵白アレルギーの発症、寛解に関与する遺伝子の網羅的な検討を、DNAマイクロアレイを用いて行い、病態の把握、診断に有用なマーカー遺伝子の探索を試みた。鶏卵アレルギー患者、非鶏卵アレルギー児を対象に、マイクロアレイ解析を行い、抗原刺激後にCD4+細胞にて、非鶏卵アレルギー児と比べて鶏卵アレルギー患者で発現が有意に増加する遺伝子としてcytokine inducible SH2-containing protein(CISH)を選択した。また、CISHはreal-time PCRの検討においても、鶏卵アレルギー児で有意な増加を示した。CISHが鶏卵アレルギーの病態形成に関与し、診断のマーカーとなる可能性が示唆された。(著者抄録)