Nagamori Tsunehisa, Ishibazawa Emi, Yoshida Yoichiro, Izumi Kengo, Sato Masayuki, Ichimura Yuki, Okiyama Naoko, Nishino Ichizo, Azuma Hiroshi
Department of Pediatrics, Asahikawa Medical University, Asahikawa, Hokkaido, Japan.
Department of Pediatrics, Asahikawa Kosei General Hospital, Asahikawa, Hokkaido, Japan.
J Med Cases. 2022 Jun;13(6):290-296. doi: 10.14740/jmc3940. Epub 2022 Jun 2.
Anti-nuclear matrix protein-2 (NXP2) antibody is associated with the severe, chronic myositis phenotype in juvenile dermatomyositis (JDM). Although hyperproduction of type I interferon is considered to play an important role in JDM, sequential changes in biomarkers associated with this pathophysiology have not yet been described in detail. An 8-year-old boy who presented with muscle weakness, heliotrope rash, and Gottron's papules was diagnosed with JDM. With regard to myositis-specific autoantibodies, anti-NXP2 was detected. Although the increase of serum myogenic enzymes was modest at onset, two courses of methyl-prednisolone (mPSL) pulse therapy followed by oral prednisolone and methotrexate were insufficient to initiate remission. Therefore, additional treatment, with intravenous cyclophosphamide (IVCY) and intravenous immunoglobulin (IVIG) was required to obtain a favorable outcome. We also retrospectively evaluated serum concentration of several cytokines: interleukin (IL)-6, soluble tumor necrotizing factor receptor (sTNFR)-1, sTNFR-2, IL-18, and CXC-motif chemokine ligand (CXCL)-10. The cytokine profile of this patient at onset showed a CXCL-10-dominant pattern. Additionally, sequential evaluation of CXCL-10 revealed an aberrantly high level of CXCL-10 persistent despite two courses of mPSL pulse therapy, and the level of this cytokine only gradually decreased after initiation of IVCY and IVIG. The hyperproduction of CXCL-10, presumably reflecting the hyperproduction of type I interferon in the affected tissue, may persist for a certain period, even after the initiation of multiple courses of mPSL pulse therapy. With regard to the fact that anti-NXP2 is associated with subcutaneous calcification, our data suggest the importance of aggressive intervention in cases of anti-NXP2-positive JDM as well as the need for the development of a more pathophysiologically specific treatment.
抗核基质蛋白2（NXP2）抗体与青少年皮肌炎（JDM）的严重慢性肌炎表型相关。虽然I型干扰素的过度产生被认为在JDM中起重要作用，但与这种病理生理学相关的生物标志物的连续变化尚未得到详细描述。一名8岁男孩出现肌肉无力、向阳疹和Gottron丘疹，被诊断为JDM。在肌炎特异性自身抗体方面，检测到抗NXP2。虽然发病时血清肌源性酶的升高不明显，但两疗程的甲泼尼龙（mPSL）冲击治疗，随后口服泼尼松龙和甲氨蝶呤，不足以引发缓解。因此，需要额外的治疗，即静脉注射环磷酰胺（IVCY）和静脉注射免疫球蛋白（IVIG），以获得良好的结果。我们还回顾性评估了几种细胞因子的血清浓度：白细胞介素（IL）-6、可溶性肿瘤坏死因子受体（sTNFR）-1、sTNFR-2、IL-18和CXC基序趋化因子配体（CXCL）-10。该患者发病时的细胞因子谱显示以CXCL-10为主。此外，对CXCL-10的连续评估显示，尽管进行了两疗程的mPSL冲击治疗，但CXCL-10水平持续异常升高，且该细胞因子水平仅在开始IVCY和IVIG治疗后才逐渐下降。CXCL-10的过度产生可能反映了受影响组织中I型干扰素的过度产生，即使在进行多疗程的mPSL冲击治疗后，也可能持续一段时间。鉴于抗NXP2与皮下钙化相关，我们的数据表明，在抗NXP2阳性的JDM病例中进行积极干预的重要性，以及开发更具病理生理学特异性治疗方法的必要性。
