LACC1 缺乏症会导致幼年关节炎和贫血。

IF 4.5 3区 医学 Q2 IMMUNOLOGY Clinical immunology Pub Date : 2024-06-27 DOI:10.1016/j.clim.2024.110290
Tingyan He , Linlin Wang , Xiaomei Huang, Ruohang Weng, Jun Yang
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引用次数: 0

摘要

目的:由功能缺失 LACC1 基因突变引起的幼年关节炎的特点是早期发病的对称性慢性关节炎,并伴有炎症标志物的升高。我们的目的是描述一名因 LACC1 新型复合杂合子变异引起多关节炎和贫血的患者的血清细胞因子水平、探索 I 型干扰素途径并评估治疗效果:收集了一名 LACC1 复合杂合子变异患者的临床数据。对诊断时、疾病发作时和治疗后的血清细胞因子水平和 IFN 刺激的细胞因子基因进行了分析。通过 RNA 分析检测了 LACC1 的全长 cDNA。对 PBMCs 进行了单细胞 RNA 测序:结果:在一名患有多关节炎和贫血的患者身上发现了 LACC1 基因的两个新变异。LACC1-cDNA 在健康对照组中正常表达,但在该患者体内未观察到 1384 bp 处的目标产生。与九名非系统性幼年特发性关节炎患者对照组相比,该患者的血清白细胞介素(IL)-6水平明显升高。患者、其母亲和对照组的 IFN 中位数分别为 118、8 和 4.9。JAK抑制剂与泼尼松或托珠单抗联合治疗后,患者获得了完全应答,包括关节症状缓解、贫血消退、IFN刺激的细胞因子基因表达减少,以及CRP、ESR、SAA和血清IL-6等炎症指标水平恢复正常:结论:LACC1可能在多种炎症信号通路中发挥关键作用。结论:LACC1可能在多种炎症信号通路中发挥关键作用。JAK抑制剂和托珠单抗的联合疗法可能对部分难治性患者有效。
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LACC1 deficiency leading to juvenile arthritis and anemia

Objective

Juvenile arthritis caused by loss-of-function LACC1 mutations is characterized by early onset of symmetric and chronic arthritis, associated with an elevation of inflammatory markers. We aimed to describe serum cytokine levels, explore the type I interferon pathway, and evaluate the efficacy of treatment in a patient presenting with polyarthritis and anemia caused by novel compound heterozygous variations in LACC1.

Methods

Clinical data of a patient with compound heterozygous variations in LACC1 was collected. Serum cytokine levels and IFN-stimulated cytokine genes were analyzed at diagnosis, at disease flare, and after treatment. Full-length cDNA of LACC1 was checked by RNA analysis. Single-cell RNA sequencing was performed in PBMCs.

Results

Two novel variants in the LACC1 gene were identified in a patient presenting with polyarthritis and anemia. LACC1-cDNA was normally expressed in the healthy control, the target production at 1384 bp was not observed in the patient. Compared to nine patient controls with non-systemic juvenile idiopathic arthritis, serum interleukin(IL)-6 level was significantly elevated in the affected patient. The median IFN score for the patient, her mother, and controls were 118, 8, and 4.9, respectively. The combined treatment of JAK inhibitors with prednisone or tocilizumab led to a complete response, including remission of joint symptoms, resolution of anemia, reduced expression of IFN-stimulated cytokine genes, and normalized levels of inflammatory markers, including CRP, ESR, SAA, and serum IL-6.

Conclusion

LACC1 may play a crucial role in multiple inflammatory signaling pathways. The combination therapy of JAK inhibitors and tocilizumab may be effective for a subset of refractory patients.

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来源期刊
Clinical immunology
Clinical immunology 医学-免疫学
CiteScore
12.30
自引率
1.20%
发文量
212
审稿时长
34 days
期刊介绍: Clinical Immunology publishes original research delving into the molecular and cellular foundations of immunological diseases. Additionally, the journal includes reviews covering timely subjects in basic immunology, along with case reports and letters to the editor.
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