Juvenile onset systemic lupus erythematosus thyroid dysfunction: A subgroup with mild disease?

The aim of this study was to evaluate the frequency of thyroid dysfunction and thyroid antibodies in patients with juvenile onset Systemic Lupus Erythematosus (JOSLE) and its association with clinical and immunological features. Seventy-seven patients with JOSLE, 64 females, median age 19 years, were consecutively enrolled from March to December 2007. Clinical data related to thyroid dysfunction and lupus were obtained by chart review and patient interview. Serum levels of TSH, free T4, anti-thyroglobulin (TgAb), anti-thyroperoxidase (TPOAb), TRAb and lupus related autoantibodies were analyzed by standard techniques. Nine patients were diagnosed as hypothyroidism and 4 hyperthyroidism. 28% JOSLE patients had moderate/high titer of thyroid antibodies: 23% TgAb, 2.6% TPOAb and 3.9% TRAb. JOSLE patients with positive thyroid autoantibodies had higher frequency of anti-U1RNP antibodies than patients without these antibodies (40.9 vs. 14.5%, OR:0.25, CI:0.08–0.76, p = 0.017). Furthermore, renal/neurological/hematological involvement was less frequently observed in patients with hypothyroidism (55.6 vs. 87.5%, OR:0.18, CI:0.04–0.81, p = 0.035) and with thyroid antibodies (68.4 vs. 90.9%, OR:0.22, CI:0.06–0.82, p = 0.027) than in patients without these alterations. No association with PTPN22 polymorphism was found. In conclusion, JOSLE patients have high prevalence of subclinical hypothyroidism. The novel association of anti-thyroid antibodies with anti-U1RNP antibodies in JOSLE seems to identify a subgroup of patients with less life-threatening organ involvement.     

HLA-DRB1*15 Confers Susceptibility to Juvenile SLE But is Not Associated with Disease Presentation: An Egyptian Study

The etiology of Systemic lupus erythematosus (SLE) seems to be multifactorial including environmental as well as genetic factors. Major histocompatibility complex (MHC) genes especially HLA-DRB1 and HLA-DQB1 are strongly implicated in susceptibility to SLE. Moreover ethnicity has been found to have a significant role in both disease susceptibility and disease expression. This study was carried out to determine HLA-DRB1 allele association with SLE susceptibility and disease presentation in Egyptian children with juvenile onset SLE. HLA-DRB1 allele typing was done using polymerase chain reaction-sequence-specific oligonucleotide probe for 65 juvenile Egyptian SLE patients and 150 healthy controls. p-values were corrected for the number of the alleles tested (Pc). HLA-DRB1*15 g allele was significantly increased in SLE children versus controls (OR = 4.76; 95% CI = 1.83–12.4; p = 0.001 and Pc = 0.012). No HLA-DRB1 allele was found to be statistically significant associated with musculoskeletal, cutaneous, hematologic, cardiac or neuropsychiatric manifestations in SLE patients (p > 0.05). Moreover no statistically significant association was found between HLA-DRB1 alleles and clinical presentation or histologic classes of lupus nephritis. The current work suggests that HLA-DRB1*15g allele may be a susceptibility allele in Egyptian children with SLE but is not related to clinical presentation of SLE.     

幼年特发性关节炎合并葡萄膜炎15例病例系列报告

背景 葡萄膜炎为幼年特发性关节炎(JIA)最常见的关节外表现,治疗不及时可导致严重并发症,有致盲风险.目的 探讨JIA合并葡萄膜炎的临床特征.设计病例系列报告.方法 纳入首都儿科研究所附属儿童医院风湿免疫科2018年3月至2020年5月收治的JIA合并葡萄膜炎患儿,从病历中截取人口学资料、实验室检查、JIA分型、眼部表...     

儿童类风湿关节炎高贡献率易感基因的研究

目的通过对小儿类风湿关节炎全基因组基因拷贝数变异(copy number variations,CNVs)的研究,为该病易感基因筛选和发病机制研究提供理论基础。方法选取小儿类风湿关节炎患者(Juvenile rheumatoid arthritis,JRA)20例作为患病组,随机从体检中心选取无类风湿关节炎患病史健康儿童20例作为健康对照组。采用测序仪分别对类风湿关节炎患病组和健康组的DNA-pool进行全基因组重测序,用生物信息学软件对测序数据进行分析。结果我们采用CNVnator软件对患病组和健康组的测序数据进行检测,发现CNV位点分别为7479个和5201个。通过生物信息学分析筛选,患病组与健康组比较发现有825个CNVs位点,其中有192个位于内含子区域,有93个位于外显子区域,19个位于上游位置,25个位于下游位置。结论本研究揭示了儿童期类风湿关节炎患者的基因组拷贝数变异的变化,并发现了编码区的KIR3DL1、CD247、PPIP5K1、MIOX、ANK3、HK3基因可能为类风湿关节炎的易感基因。     

幼年型粒单核细胞白血病19例分析并文献复习

目的分析幼年型粒单核细胞白血病(JMML)的临床特点。方法对19例JMML患儿的临床资料进行分析。结果 (1)JMML临床主要以发热、腹胀为主要症状,多见肝脾肿大。(2)外周血平均白细胞计数为37.29×109/L,血红蛋白平均80.7 g/L,血小板平均72.7×109/L,单核细胞绝对值均增高(>1.0×109/L)。(3)JMML均有HbF增高。(4)无Ph染色体。结论 JMML临床少见,依据目前诊断标准诊断不难,本病预后不良,目前唯一可以治愈本病的方法是异基因造血干细胞移植,而靶向治疗尚处于体外试验阶段。     

Quantitative MR characterization of disease activity in the knee in children with juvenile idiopathic arthritis: a longitudinal pilot study

Background The development of a quantifiable and noninvasive method of monitoring disease activity and response to therapy is vital for arthritis management. Objective The purpose of this study was to investigate the utility of quantitative dynamic contrast-enhanced MRI (DCE-MRI) based on pharmacokinetic (PK) modeling to evaluate disease activity in the knee and correlate the results with the clinical assessment in children with juvenile idiopathic arthritis (JIA). Materials and methods A group of 17 children with JIA underwent longitudinal clinical and laboratory assessment and DCE-MRI of the knee at enrollment, 3 months, and 12 months. A PK model was employed using MRI signal enhancement data to give three parameters, K^{trans ′} (min⁻¹), k_ep (min⁻¹), and V_p ^′ and to calculate synovial volume. Results The PK parameters, synovial volumes, and clinical and laboratory assessments in most children were significantly decreased (P < 0.05) at 12 months when compared to the enrollment values. There was excellent correlation between the PK and synovial volume and the clinical and laboratory assessments. Differences in MR and clinical parameter values in individual subjects illustrate persistent synovitis when in clinical remission. Conclusion A decrease in PK parameter values obtained from DCE-MRI in children with JIA likely reflects diminution of disease activity. This technique may be used as an objective follow-up measure of therapeutic efficacy in patients with JIA. MR imaging can detect persistent synovitis in patients considered to be in clinical remission.     

细胞免疫在幼年特发性关节炎发病机制中的作用

幼年特发性关节炎(JIA)是儿童时期常见的一种以慢性关节炎为主要特点的自身免疫性疾病,其发病机制尚不明确,而其免疫发病机制是目前研究的重点,以往研究多集中在体液免疫方面,目前的研究认为细胞免疫在JIA的发病过程中起重要作用.T淋巴细胞、巨噬细胞、树突状细胞(DC)、NK细胞、中性粒细胞、血小板及红细胞均是参与细胞免疫过程的细胞,在JIA慢性炎症的维持及关节损害中发挥着重要的作用.     

Frontal cognitive dysfunction in juvenile myoclonic epilepsy

PURPOSE: The aim of the present study was to investigate the possible frontal cognitive dysfunction in patients with juvenile myoclonic epilepsy (JME) and to compare the results with those of patients with frontal lobe epilepsy (FLE) and temporal lobe epilepsy (TLE), as well as with controls. METHODS: A total of 50 patients with JME, 40 patients with FLE, 40 patients with TLE, and 40 normal controls, all matched for age, education, and IQ, were administered tests to assess frontal functions (the Word Fluency Test and the Wisconsin Card Sorting Test [WCST]). All participants had a normal intelligence level based on the Wechsler Adult Intelligence Scale, and did not take medications other than antiepileptics (AEDs) or have a psychiatric history. RESULTS: Patients with JME had severe impairment in all administered tasks, similar to that of patients with FLE; TLE patients and controls followed in order. Multiple regression analysis did not disclose any significant effect of clinical variables on the cognitive deficits. DISCUSSION: These results clearly suggest that JME patients can show some frontal dysfunction, which may affect both epileptogenic features and cognitive processes. Further studies are needed to confirm these findings.     

Spinal interleukin-6 contributes to central sensitisation and persistent pain hypersensitivity in a model of juvenile idiopathic arthritis

Pain is the most debilitating symptom in juvenile idiopathic arthritis. As pain correlates poorly to the extent of joint pathology, therapies that control joint inflammation are often inadequate as analgesics. We test the hypothesis that juvenile joint inflammation leads to sensitisation of nociceptive circuits in the central nervous system, which is maintained by cytokine expression in the spinal cord. Here, transient joint inflammation was induced in postnatal day (P)21 and P40 male Sprague-Dawley rats with a single intra-articular ankle injection of complete Freund’s adjuvant. Hindpaw mechanical pain sensitivity was assessed using von Frey hair and weight bearing tests. Spinal neuron activity was measured using in vivo extracellular recording and immunohistochemistry. Joint and spinal dorsal horn TNFα, IL1β and IL6 protein expression was quantified using western blotting. We observed greater mechanical hyperalgesia following joint inflammation in P21 compared to P40 rats, despite comparable duration of swelling and joint inflammatory cytokine levels. This is mirrored by spinal neuron hypersensitivity, which also outlasted the duration of active joint inflammation. The cytokine profile in the spinal cord differed at the two ages: prolonged upregulation of spinal IL6 was observed in P21, but not P40 rats. Finally, spinal application of anti-IL-6 antibody (30 ng) reduced the mechanical hyperalgesia and neuronal activation. Our results indicate that persistent upregulation of pro-inflammatory cytokines in the spinal dorsal horn is associated with neuronal sensitisation and mechanical hyperalgesia in juvenile rats, beyond the progress of joint pathology. In addition, we provide proof of concept that spinal IL6 is a key target for treating persistent pain in JIA.     

The effect of disc repositioning and post-operative functional splint for the treatment of anterior disc displacement in juvenile patients with Class II malocclusion

Purpose

To evaluate the effect of temporomandibular joint (TMJ) disc repositioning and post-operative functional splint for the treatment of anterior disc displacement (ADD) in juvenile patients with Class II malocclusion.