論文

The ultrastructural characteristics and immunolocalization of in vivo bound immunoglobulin G (IgG) in skin affected by anti-p200 pemphigoid have not been elucidated. To give insight into the mechanism of blister formation we report a new case of anti-p200 pemphigoid, studied with stage-oriented morphological analysis and immunoelectron microscopy. Skin biopsy specimens were evaluated ultrastructurally and histologically with immunohistochemistry. By observing the nonblister site, the blister edge and centre of the blister, we determined that neutrophil infiltration increases gradually at the dermoepidermal junction in association with the destruction of type IV collagen. Ultrastructurally, many neutrophils were observed under the lamina densa, with vacuole formation in the dermis. At the periphery of the blister, the lamina densa became fragmented and was observed either at the roof or the floor of the blister. At the centre of the blister, the lamina densa was mainly observed at the blister floor. Postembedding immunoelectron microscopy demonstrated that the IgG, bound in vivo, localized at the lamina lucida, while the area beneath the hemidesmosomes was spared. Together with the early involvement of neutrophils and the destruction of the basal lamina, we suggest that the binding of autoantibodies to the nonhemidesmosomal lamina lucida may induce inflammation with neutrophils, resulting in blister formation.

BACKGROUND: Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are potentially fatal blistering diseases caused by autoantibodies targeting desmoglein (Dsg) adhesion proteins. Previous studies have shown an IgG4 > IgG1 predominance of anti-Dsg antibodies in pemphigus; however, no studies have examined total serum IgG4 levels in pemphigus. IgG4 is induced by chronic antigen stimulation, which could occur with persistent skin blistering and potentially elevate the total serum IgG4 relative to other IgG subclasses in patients with pemphigus. OBJECTIVES: The primary aim of the study was to quantitate total and Dsg-specific IgG subclasses in patients with pemphigus. METHODS: IgG subclasses and Dsg-specific IgG1 and IgG4 were quantitated in patients with PV and PF, and in sera from age-matched controls using a subclass enzyme-linked immunosorbent assay. The effectiveness of IgG4 depletion in blocking IgG pathogenicity in PV was determined using a keratinocyte dissociation assay. RESULTS: Dsg-specific antibodies comprised a median of 7.1% and 4.2% of total IgG4 in patients with PV and PF, respectively, with eightfold and fourfold enrichment in IgG4 vs. IgG1. Total serum IgG4, but not other IgG subclasses, was enriched in patients with PV and PF compared with age-matched controls (P = 0.004 and P = 0.005, respectively). IgG4 depletion of PV sera reduced pathogenicity in a keratinocyte dissociation assay and showed that affinity-purified IgG4 is more pathogenic than other serum IgG fractions. CONCLUSIONS: Dsg-specific autoantibodies are significantly enriched in IgG4, which may explain the enrichment of total serum IgG4 in some patients with pemphigus. By preferentially targeting autoimmune rather than beneficial immune antibodies, IgG4-targeted therapies may offer safer treatment options for pemphigus.

An extremely rare case of intractable ulcer caused by Mycobacterium shinshuense is described. A 59-year-old Japanese woman developed an ulcerated subcutaneous induration on the upper arm. Ziehl-Neelsen staining revealed positive bacilli. Tissue culture isolated Mycobacterium species, but standard identification techniques (including molecular biological approaches such as DNA-DNA hybridization) could not distinguish the precise causative pathogen, although it was narrowed down to three possibilities: Mycobacterium marinum, Mycobacterium ulcerans and M. shinshuense. Finally, a novel 16S rRNA sequencing method enabled the diagnosis of M. shinshuense infection. The epidemiology of the cutaneous infection caused by this mycobacterium has yet to be elucidated, but a review of reported cases indicated that ulcers having some resemblance to those caused by M. ulcerans infection were found in nonendemic areas and that M. shinshuense could be considered as the cause. The approach introduced in this report could provide a powerful tool for the identification of this organism.

ダカルバジンを含む化学療法に不応となったIV期悪性黒色腫9例に海外で主に2nd lineの化学療法として使用されるカルボプラチン＋パクリタキセル（CP）療法を施行した．1例が部分奏効（PR），3例が安定（SD），5例が進行（PD）し，無増悪生存期間（PFS）中央値は2.8カ月，全生存期間中央値は10.6カ月であった．忍容性は一般に良好で，44%の症例がCP療法により制御（PR＋SD）され，PRとSD症例のPFSは7.0～11.6カ月とPD症例よりも有意に長かったことから，本邦においてもCP療法はIV期悪性黒色腫に対する救済化学療法の1つになりうることが示唆された．

尋常性天疱瘡（PV）は抗デスモグレイン（Dsg）抗体により皮膚や粘膜に水疱，びらんを呈する疾患である．脱毛もPVの症状とされるが頻度は少ない．我々は脱毛を伴うPVの症例を経験し，その特徴や臨床的意義の明確化を試みた．特記すべきは脱毛斑ではなく外毛根鞘を付けた成長期毛が抵抗なく抜去される易脱毛性であった．採取毛の表皮細胞間にはIgGが沈着し，Dsg1, 3の発現の低い部分に棘融解像が見られた．また皮膚所見の軽快とともに抜毛されなくなったことから，PVの脱毛の本態はNikolsky現象であり，その評価は臨床経過のモニタリングに有用と考えられた．