UNASSIGNED: Henoch-Schönlein purpura (HSP) is the most common systemic vasculitis in children. HSP is a multifactorial inflammatory disease, but its pathogenesis is still unclear. The pathogenicity of familial Mediterranean fever gene (MEFV) variants in HSP remains controversial. The objective of this study was to evaluate relationships between MEFV variants and susceptibility to HSP and their associations with clinical outcomes. We also investigated levels of IL-33 and soluble suppression of tumorigenicity 2 (sST2) in children with HSP and their clinical significance.
UNASSIGNED: We selected 100 children with HSP as the case group. The control group consisted of 50 children who visited the hospital for physical health examinations. All subjects were screened for MEFV gene exon mutations, and levels of IL-33 and sST2 were measured.
UNASSIGNED: The frequency of MEFV variants was significantly greater in HSP patients than in healthy controls. The variant with the highest frequency was E148Q. The frequency of the C allele of the MEFV variant E148Q was 32 % in HSP patients and 18 % in controls (P-adjust = 0.04). Patients with the MEFV E148Q variant had more frequent joint involvement and recurrent purpura and higher levels of IL-33 and C-reactive protein (CRP). Levels of IL-33 and sST2 in children with HSP were significantly higher than those in the control group, and the sST2/IL-33 ratio in children with HSP was unbalanced (P-adjust <0.05). Logistic regression analysis revealed the presence of E148Q and an unbalanced sST2/IL-33 ratio to be independent risk factors for HSP.
UNASSIGNED: The results of this study suggest that the MEFV variant E148Q is associated with HSP susceptibility in Chinese children and that carriers of the variant may have more severe clinical manifestations and greater inflammatory responses. E148Q and the sST2/IL-33 ratio may play important roles in the pathogenesis of HSP.

暂无摘要。

UNASSIGNED: Yao syndrome (YAOS, OMIM 617321) was formerly designated as nucleotide-binding oligomerization domain-containing protein-2 (NOD2)-associated autoinflammatory disease (NAID). This disorder shares similar clinical phenotypes with hereditary periodic fever syndromes (HPFS). This study aimed to compare YAOS with familial Mediterranean fever (FMF).
UNASSIGNED: In this retrospective study, electronic medical records of a case series of YAOS were reviewed and data were analyzed. All patients underwent genetic testing for periodic fever syndrome 6-gene panel.
UNASSIGNED: A total of 6 cases were presented. These patients were initially thought to have MEditerranean FeVer (MEFV)-negative FMF and received treatment with colchicine. They were eventually diagnosed with YAOS. The differences between these diseases were illustrated. In addition, both MEFV and NOD2 mutations were detected in some patients and family members. Patients with carriage of both gene mutations may present with heterogeneous disease expression. A close correlation between phenotypes and genotypes is needed to make a diagnosis.
UNASSIGNED: YAOS may mimic FMF. Molecular analysis should cover NOD2 whole gene sequencing to help distinguish these diseases. Both NOD2 and MEFV mutations may contribute to disease expression in an individual.

Clinicians should consider that clinical exome sequencing provides the unique potential to disentangle complex phenotypes into multiple genetic etiologies. Further, functional studies on variants of uncertain significance are necessary to arrive at an accurate diagnosis for the patient.

BACKGROUND: In a previous study, we demonstrated that asthma patients with signs of emphysema on quantitative computed tomography (CT) fulfill the diagnosis of asthma-COPD overlap syndrome (ACOS). However, quantitative CT measurements of emphysema are not routinely available for patients with chronic airway disease, which limits their application. Spirometry was a widely used examination tool in clinical settings and shows emphysema as a sharp angle in the maximum expiratory flow volume (MEFV) curve, called the \"angle of collapse (AC)\". The aim of this study was to investigate the value of the AC in the diagnosis of emphysema and ACOS.
METHODS: This study included 716 participants: 151 asthma patients, 173 COPD patients, and 392 normal control subjects. All the participants underwent pulmonary function tests. COPD and asthma patients also underwent quantitative CT measurements of emphysema. The AC was measured using computer models based on Matlab software. The value of the AC in the diagnosis of emphysema and ACOS was evaluated using receiver-operating characteristic (ROC) curve analysis.
RESULTS: The AC of COPD patients was significantly lower than that of asthma patients and control subjects. The AC was significantly negatively correlated with emphysema index (EI; r=-0.666, P<0.001), and patients with high EI had a lower AC than those with low EI. The ROC curve analysis showed that the AC had higher diagnostic efficiency for high EI (area under the curve =0.876) than did other spirometry parameters. In asthma patients, using the AC ≤137° as a surrogate criterion for the diagnosis of ACOS, the sensitivity and specificity were 62.5% and 89.1%, respectively.
CONCLUSIONS: The AC on the MEFV curve quantified by computer models correlates with the extent of emphysema. The AC may become a surrogate marker for the diagnosis of emphysema and help to diagnose ACOS.

The aim of this study was to investigate the association between single-nucleotide polymorphisms (SNP) within MEFV gene and Henoch-Schönlein purpura (HSP) risk, and the impact of SNP-SNP interaction on HSP risk in Chinese children. A total of 662 subjects with a mean age of 7.9 ± 2.4 years old were selected, including 320 HSP patients and 342 normal controls. Logistic regression was performed to investigate association between SNP and HSP risk, and generalized multifactor dimensionality reduction (GMDR) was used to analyze the SNP-SNP interaction. Logistic analysis showed a significant association between genotypes of variants in rs3743930 and increased HSP risk. The carriers of homozygous mutant of rs3743930 polymorphism revealed increased HSP risk than those with wild-type homozygotes; OR (95% CI) was 1.55 (1.23-1.85). GMDR analysis suggested a significant two-locus model (p = 0.0107) involving rs3743930 and rs28940580, indicating a potential SNP-SNP interaction between rs3743930 and rs28940580. Overall, the two-locus models had a cross-validation consistency of 10 of 10 and had the testing accuracy of 60.72%. Subjects with rs3743930-GC or CC and rs28940580-GA or AA genotype have the highest HSP risk, compared to subjects with rs3743930-GG and rs28940580-GG genotype; OR (95% CI) was 2.13 (1.52-2.89). The variants in rs3743930 and interaction between rs3743930 and rs28940580 were associated with increased HSP risk in Chinese children.

Ankylosing spondylitis (AS) and familial Mediterranean fever (FMF) are a common autoimmune disease and a classic autoinflammatory disease, respectively. Mediterranean fever (MEFV) encodes the pyrin protein and is the causal disease gene in FMF. This protein is an important regulator of innate immunity and may play a key role in the development of AS. To identify the mutations in the B30.2 domain of pyrin and to uncover the relationships between these mutations and AS risk in the Chinese Han population, we extracted genomic DNA from the peripheral blood of 200 AS patients and 200 matched controls and performed polymerase chain reactions (PCRs) and direct sequencing on those samples. Statistical analysis indicated that only Met694Val (rs61752717) in the B30.2 domain of pyrin could affect the risk of AS (P = 0.042; odds ratio [OR] = 5.103; 95% confidence interval [CI] = 1.111-23.437 for the model of Met (M) vs. Val (V), P = 0.040; OR = 5.211; 95% CI = 1.127-24.091 for the model of MM vs. MV+VV). Moreover, M694V is significantly associated with a higher level of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) in AS patients. Our results are the first to suggest that the M694V allele of the pyrin was associated with AS risk in the Chinese Han population and that this mutation may be associated with the inflammatory response in the development of AS.