Lesional and Nonlesional Skin From Patients With Untreated Juvenile Dermatomyositis Displays Increased Numbers of Mast Cells and Mature Plasmacytoid Dendritic Cells
Lesional and Nonlesional Skin From Patients With Untreated Juvenile Dermatomyositis Displays Increased Numbers of Mast Cells and Mature Plasmacytoid Dendritic Cells
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DOI：
10.1002/art.27529
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发表时间：
2010-09-01
影响因子：
--
通讯作者：
Pachman, Lauren M.
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文献类型：
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作者：
Shrestha, Sheela;Wershil, Barry;Pachman, Lauren M.
目标。研究未经治疗的青少年皮肌炎（DM）患儿成对肌肉和皮肤（病变/非病变）中肥大细胞和树突状细胞（DC）亚群的分布。将7例可能/明确的幼年型糖尿病患者的肌肉和皮肤活检样本（4例伴有活动性皮疹的皮肤活检样本）与10例健康儿童对照的肌肉和皮肤样本进行比较。甲苯胺蓝染色评估肥大细胞分布和数量，学生t检验分析。采用针对DC-LAMP、血树突状细胞抗原1 （BDCA-1）和BDCA-2的抗体进行免疫组化分析，分别鉴定成熟的树突状细胞、髓样树突状细胞（MDCs）和浆细胞样树突状细胞（PDCs）。黏液病毒抗性蛋白A （MxA）染色提示I型干扰素（IFN）信号活跃；阳性染色半定量评分，采用Mann-Whitney U检验分析。少年型糖尿病患者的炎症和非病变皮肤都比儿童对照组含有更多的肥大细胞（P = 0.029），病变和非病变皮肤中肥大细胞的数量相当。有趣的是，幼年型糖尿病患者皮肤的肥大细胞数量比成对肌肉组织的肥大细胞数量多（P = 0.014），而幼年型糖尿病患者肌肉的肥大细胞数量与对照肌肉相比没有增加。青少年期DM患者的肌肉和皮肤的成熟PDCs和MxA染色均高于对照组织（P < 0.05）。在青少年糖尿病患者的肌肉和皮肤以及儿童对照肌肉中，MDCs少于PDCs，并且在儿童对照皮肤样本中MDCs和PDCs的分布相似。肥大细胞存在于幼年型糖尿病患者的皮肤中（与皮疹无关），但不存在于成对的肌肉组织中，这表明肥大细胞在幼年型糖尿病皮肤病理生理中具有特殊作用。在幼年型糖尿病患者的皮肤中，PDCs数量的增加和I型ifn诱导蛋白表达的增加表明对T细胞分化和随后的效应功能有选择性影响。
Objective. To investigate the distribution of mast cells and dendritic cell (DC) subsets in paired muscle and skin (lesional/nonlesional) from untreated children with juvenile dermatomyositis (DM).Methods. Muscle and skin biopsy samples (4 skin biopsy samples with active rash) from 7 patients with probable/definite juvenile DM were compared with muscle and skin samples from 10 healthy pediatric controls. Mast cell distribution and number were assessed by toluidine blue staining and analyzed by Student's t-test. Immunohistochemical analysis was performed to identify mature DCs, myeloid DCs (MDCs), and plasmacytoid DCs (PDCs) by using antibodies against DC-LAMP, blood dendritic cell antigen 1 (BDCA-1), and BDCA-2, respectively. Myxovirus resistance protein A (MxA) staining indicated active type I interferon (IFN) signaling; positive staining was scored semiquantitatively and analyzed using the Mann-Whitney U test.Results. Both inflamed and nonlesional skin from patients with juvenile DM contained more mast cells than did skin from pediatric controls (P = 0.029), and comparable numbers of mast cells were present in lesional and nonlesional skin. Interestingly, mast cell numbers were greater in skin than in paired muscle tissue from patients with juvenile DM (P = 0.014) and were not increased in muscle from patients with juvenile DM compared with control muscle. Both muscle and skin from patients with juvenile DM showed more mature PDCs and MxA staining than did their corresponding control tissues (P < 0.05). In both muscle and skin from patients with juvenile DM and in pediatric control muscle, there were fewer MDCs than PDCs, and the distributions of MDCs and PDCs were similar in pediatric control skin samples.Conclusion. The identification of mast cells in skin (irrespective of rash) from patients with juvenile DM, but not in paired muscle tissue, suggests that they have a specific role in juvenile DM skin pathophysiology. In skin from patients with juvenile DM, increased numbers of PDCs and increased expression of type I IFN-induced protein suggest a selective influence on T cell differentiation and subsequent effector function.