PDF(Pubmed)
Abstract：
UNASSIGNED: Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA syndrome), and Kawasaki disease (KD) are both considered to be disorders of the innate immune system, and the potential role of inflammasome activation in the immunopathogenesis of both diseases has been previously described.
UNASSIGNED: Herein, we report the clinical courses of three patients who presented a rare combination of PFAPA syndrome and KD. Two patients who presented KD later developed the PFAPA syndrome, of whom one developed recurrent KD 2 years after the initial diagnosis. The third patient developed KD one year after the onset of PFAPA syndrome. The presence of both of these conditions within individual patients, combined with the knowledge that inflammasome activation is involved in both PFAPA syndrome and KD, suggests a shared background of inflammatory dysregulation. To elucidate the mechanism underlying shared inflammatory dysregulation, we investigated the roles of Nod-like receptors (NLRs) and their downstream inflammasome-related genes. All the patients had a frameshift variant in CARD8 (CARD8-FS). A previous study demonstrated a higher frequency of CARD8-FS, whose product loses CARD8 activity and activates the NLRP3 inflammasome, in patients with the PFAPA syndrome. Additionally, the NLRP3 inflammasome is known to be activated in patients with KD. Together, these results suggest that the CARD8-FS variant may also be essential in KD pathogenesis. As such, we analyzed the CARD8 variants among patients with KD. However, we found no difference in the variant frequency between patients with KD and the general Japanese population.
UNASSIGNED: We report the clinical courses of three patients with a rare combination of PFAPA syndrome and KD. All the patients had the CARD8-FS variant. However, we could not find a difference in the variant frequency between patients with KD and the general Japanese population. As the frequency of KD is much higher than that of PFAPA among Japanese patients, and the cause of KD is multifactorial, it is possible that only a small portion of patients with KD harbor CARD8-FS as a causative gene.
UNASSIGNED: Herein, we report the clinical courses of three patients who presented a rare combination of PFAPA syndrome and KD. Two patients who presented KD later developed the PFAPA syndrome, of whom one developed recurrent KD 2 years after the initial diagnosis. The third patient developed KD one year after the onset of PFAPA syndrome. The presence of both of these conditions within individual patients, combined with the knowledge that inflammasome activation is involved in both PFAPA syndrome and KD, suggests a shared background of inflammatory dysregulation. To elucidate the mechanism underlying shared inflammatory dysregulation, we investigated the roles of Nod-like receptors (NLRs) and their downstream inflammasome-related genes. All the patients had a frameshift variant in CARD8 (CARD8-FS). A previous study demonstrated a higher frequency of CARD8-FS, whose product loses CARD8 activity and activates the NLRP3 inflammasome, in patients with the PFAPA syndrome. Additionally, the NLRP3 inflammasome is known to be activated in patients with KD. Together, these results suggest that the CARD8-FS variant may also be essential in KD pathogenesis. As such, we analyzed the CARD8 variants among patients with KD. However, we found no difference in the variant frequency between patients with KD and the general Japanese population.
UNASSIGNED: We report the clinical courses of three patients with a rare combination of PFAPA syndrome and KD. All the patients had the CARD8-FS variant. However, we could not find a difference in the variant frequency between patients with KD and the general Japanese population. As the frequency of KD is much higher than that of PFAPA among Japanese patients, and the cause of KD is multifactorial, it is possible that only a small portion of patients with KD harbor CARD8-FS as a causative gene.
摘要：
■周期性发烧，口疮性口炎，咽炎,和颈椎炎（PFAPA综合征），和川崎病（KD）都被认为是先天免疫系统的疾病，先前已经描述了炎症小体激活在两种疾病的免疫发病机制中的潜在作用。
■这里，我们报道了3例出现罕见的PFAPA综合征和KD组合的患者的临床过程.两名出现KD的患者后来发展为PFAPA综合征，其中一人在初次诊断后2年出现复发性KD。第三名患者在PFAPA综合征发作一年后发展为KD。这两种情况在个体患者中的存在，结合炎症小体激活参与PFAPA综合征和KD的知识，提示炎症失调的共同背景。为了阐明共同炎症失调的潜在机制，我们研究了Nod样受体（NLRs）及其下游炎症相关基因的作用。所有患者在CARD8（CARD8-FS）中有移码变异。先前的研究表明CARD8-FS的频率更高，其产品失去CARD8活性并激活NLRP3炎性体，PFAPA综合征患者。此外,已知KD患者的NLRP3炎性体被激活.一起,这些结果表明,CARD8-FS变异体也可能在KD发病机制中发挥重要作用.因此，我们分析了KD患者的CARD8变异.然而,我们发现KD患者和日本普通人群的变异频率没有差异.
■我们报告了3例罕见的PFAPA综合征和KD患者的临床过程。所有患者都有CARD8-FS变异。然而,我们没有发现KD患者与日本普通人群之间的变异频率有差异.由于日本患者中KD的频率远高于PFAPA，KD的原因是多方面的，可能只有一小部分KD患者携带CARD8-FS作为致病基因.
■这里，我们报道了3例出现罕见的PFAPA综合征和KD组合的患者的临床过程.两名出现KD的患者后来发展为PFAPA综合征，其中一人在初次诊断后2年出现复发性KD。第三名患者在PFAPA综合征发作一年后发展为KD。这两种情况在个体患者中的存在，结合炎症小体激活参与PFAPA综合征和KD的知识，提示炎症失调的共同背景。为了阐明共同炎症失调的潜在机制，我们研究了Nod样受体（NLRs）及其下游炎症相关基因的作用。所有患者在CARD8（CARD8-FS）中有移码变异。先前的研究表明CARD8-FS的频率更高，其产品失去CARD8活性并激活NLRP3炎性体，PFAPA综合征患者。此外,已知KD患者的NLRP3炎性体被激活.一起,这些结果表明,CARD8-FS变异体也可能在KD发病机制中发挥重要作用.因此，我们分析了KD患者的CARD8变异.然而,我们发现KD患者和日本普通人群的变异频率没有差异.
■我们报告了3例罕见的PFAPA综合征和KD患者的临床过程。所有患者都有CARD8-FS变异。然而,我们没有发现KD患者与日本普通人群之间的变异频率有差异.由于日本患者中KD的频率远高于PFAPA，KD的原因是多方面的，可能只有一小部分KD患者携带CARD8-FS作为致病基因.
