Kiuru-Enari S, Keski-Oja J, Haltia M
Department of Neurology, Helsinki University Central Hospital, Haartmaninkatu 4, FIN-00290 Helsinki, Finland.
Br J Dermatol. 2005 Feb;152(2):250-7. doi: 10.1111/j.1365-2133.2004.06276.x.
Hereditary gelsolin amyloidosis (AGel amyloidosis) is an age-associated systemic disease with global distribution, caused by a G654A or G654T gelsolin gene mutation. Cutis laxa is a principal clinical manifestation of this disease. However, only few data on the dermatological involvement are available, and the pathogenesis of this amyloidosis-associated form of cutis laxa has remained unknown.
To elucidate the pathomechanism of this less well-known genodermatosis.
We performed systematic clinical, histological, immunohistochemical and ultrastructural skin biopsy studies in 12 patients with a G654A gelsolin gene mutation. For comparison, skin specimens from 10 control subjects were analysed.
All patients had clinically characteristic cutis laxa, and frequently other signs of symptomatic skin disease such as increased fragility and risk for intracutaneous bleeding. All patients showed cutaneous deposition of gelsolin amyloid (AGel), mainly attached to basement membranes or basal laminae of various cutaneous structures, dermal nerves and blood vessel walls, and elastic fibres, particularly in the lower reticular dermis. AGel often encircled the elastic fibres, and colocalized with amyloid P component (AP), an elastic fibre microfibrillar sheath-associated protein. Fragmentation and loss of elastic fibres, epidermal atrophy, and reduction of dermal appendages were also common. Antibodies to wild-type gelsolin bound to S-100-positive epidermal dendritic cells, a previously unrecognized immunoreaction. Patients had fewer gelsolin-positive dendritic cells than controls.
Widespread skin involvement with AGel deposition and elastic fibre involvement are essential pathological features in AGel amyloidosis, and contribute to the characteristic cutis laxa, dramatic in old age. Codistribution of AGel and AP, with demonstrated specific binding affinity for amyloid fibrils, suggests that elastic fibre-associated AP acts as a matrix for cutaneous amyloid deposition in AGel amyloidosis.
遗传性凝溶胶蛋白淀粉样变性（AGel淀粉样变性）是一种与年龄相关的全身性疾病，全球均有分布，由凝溶胶蛋白基因G654A或G654T突变引起。皮肤松弛是该疾病的主要临床表现。然而，关于皮肤受累的资料很少，且这种与淀粉样变性相关的皮肤松弛的发病机制尚不清楚。
阐明这种鲜为人知的遗传性皮肤病的发病机制。
我们对12例携带G654A凝溶胶蛋白基因突变的患者进行了系统的临床、组织学、免疫组织化学和超微结构皮肤活检研究。作为对照，分析了10名对照受试者的皮肤标本。
所有患者均有临床特征性的皮肤松弛，且常伴有其他症状性皮肤病体征，如皮肤脆性增加和皮内出血风险。所有患者均显示凝溶胶蛋白淀粉样物质（AGel）在皮肤沉积，主要附着于各种皮肤结构、真皮神经和血管壁以及弹性纤维的基底膜或基底层，尤其是在真皮下部网状层。AGel常环绕弹性纤维，并与淀粉样P成分（AP）共定位，AP是一种与弹性纤维微原纤维鞘相关的蛋白质。弹性纤维断裂和缺失、表皮萎缩以及皮肤附属器减少也很常见。野生型凝溶胶蛋白抗体与S-100阳性表皮树突状细胞结合，这是一种以前未被认识的免疫反应。患者的凝溶胶蛋白阳性树突状细胞比对照组少。
AGel沉积广泛累及皮肤和弹性纤维受累是AGel淀粉样变性的基本病理特征，导致了特征性的皮肤松弛，在老年时更为明显。AGel和AP的共分布以及对淀粉样纤维的特异性结合亲和力表明，弹性纤维相关的AP在AGel淀粉样变性中作为皮肤淀粉样沉积的基质。
