[A preliminary study on the role of V-domain Ig suppressor of T cell activation in juvenile idiopathic arthritis]. / Tç»†èƒžæ´»åŒ–å ç–«çƒè›‹ç™½æŠ‘åˆ¶Våž‹ç»“æž„åŸŸåœ¨å¹¼å¹´ç‰¹å‘æ€§å ³èŠ‚ç‚Žä¸­ä½œç”¨çš„åˆæ­¥ç ”ç©¶.

OBJECTIVES: To study the expression of V-domain Ig suppressor of T cell activation (VISTA) in peripheral blood of children with juvenile idiopathic arthritis (JIA) and its role in the pathogenesis of JIA. METHODS: In this prospective study, peripheral blood was collected from 47 children with different subtypes of JIA and 10 healthy children. Flow cytometry was used to measure the expression levels of VISTA, interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α) on CD14+ mononuclear cells, CD4+ T lymphocytes, and CD8+ T lymphocytes. RESULTS: The children with JIA had a significantly lower expression level of VISTA than the healthy children (P<0.05). There was a significant difference in the expression of VISTA between the children with different subtypes of JIA, with the lowest expression level in those with systemic JIA (P<0.05). There was also a significant difference in the expression of VISTA between different immune cells, with a significantly higher expression level on the surface of monocytes (P<0.05). Correlation analysis showed that VISTA was negatively correlated with the expression of IFN-γ and TNF-α on CD4+ T cells (r=-0.436 and -0.382 respectively, P<0.05), CD8+ T cells (r=-0.348 and -0.487 respectively, P<0.05), and CD14+ mononuclear cells (r=-0.582 and -0.603 respectively, P<0.05). CONCLUSIONS: The insufficient expression of VISTA may be associated with the pathogenesis of JIA, and enhancing the immunomodulatory effect of VISTA might be one option for the treatment of JIA in the future.

[Role of CD4+NKG2D+ T cells in the disease activity of juvenile idiopathic arthritis]. / CD4+NKG2D+ Tç»†èƒžåœ¨å¹¼å¹´ç‰¹å‘æ€§å ³èŠ‚ç‚Žç–¾ç— æ´»åŠ¨ä¸­çš„ä½œç”¨.

OBJECTIVES: To study the expression levels of CD4+NKG2D+ T cells and NKG2D soluble ligands, the soluble MHC class I chain-related molecules A and B (sMICA/sMICB) in the active stage and stable stage of juvenile idiopathic arthritis (JIA) and their role in the disease activity of JIA. METHODS: Nineteen children with systemic JIA and 20 children with articular JIA who were diagnosed in Children's Hospital of Chongqing Medical University from November 2019 to December 2021 were enrolled in this prospective study. Six healthy children were enrolled as the control group. After peripheral blood samples were collected, ELISA was used to measure the levels of sMICA and sMICB, and flow cytometry was used to measure the percentage of CD4+NKG2D+ T cells. Systemic Juvenile Arthritis Disease Activity Score-27 (sJADAS-27)/Juvenile Arthritis Disease Activity Score-27 (JADAS-27) was used to evaluate the disease activity in children with JIA. The Pearson correlation analysis and the receiver operating characteristic (ROC) curve were used to assess the role of CD4+NKG2D+ T cells, sMICA and sMICB in the disease activity of JIA. RESULTS: The active systemic JIA and active articular JIA groups had a significant increase in the percentage of CD4+NKG2D+ T cells compared with the control group and their corresponding inactive JIA group (P<0.05). The JIA groups had significantly higher levels of sMICA and sMICB than the control group (P<0.05), and the active articular JIA group had a significantly higher level of sMICB than the stable articular JIA group (P<0.05). In the children with JIA, the percentage of CD4+NKG2D+ T cells and the levels of sMICA and sMICB were positively correlated with sJADAS-27/JADAS-27 disease activity scores (P<0.05). The ROC curve analysis showed that sMICB had an area under the curve of 0.755 in evaluating the disease activity of JIA, with a specificity of 0.90 and a sensitivity of 0.64. CONCLUSIONS: The percentage of CD4+NKG2D+ T cells and the levels of sMICA and sMICB increase in children with JIA compared with healthy children and are positively correlated with the disease activity of JIA, suggesting that CD4+NKG2D+ T cells and NKG2D ligands can be used as potential biomarkers for evaluating the disease activity of JIA.

A Cohort Study on Deficiency of ADA2 from China.

PURPOSE: Deficiency of adenosine deaminase 2 (DADA2), an autosomal recessive autoinflammatory disorder caused by biallelic loss-of-function variants in adenosine deaminase 2 (ADA2), has not been systemically investigated in Chinese population yet. We aim to further characterize DADA2 cases in China. METHODS: A retrospective analysis of patients with DADA2 identified through whole exome sequencing (WES) at seventeen rheumatology centers across China was conducted. Clinical characteristics, laboratory findings, genotype, and treatment response were analyzed. RESULTS: Thirty patients with DADA2 were enrolled between January 2015 and December 2021. Adenosine deaminase 2 enzymatic activity was low in all tested cases to confirm pathogenicity. Median age of disease presentation was 4.3 years and the median age at diagnosis was 7.8 years. All but one patient presented during childhood and two subjects died from complications of their disease. The patients most commonly presented with systemic inflammation (92.9%), vasculitis (86.7%), and hypogammaglobinemia (73.3%) while one patient presented with bone marrow failure (BMF) with variable cytopenia. Twenty-three (76.7%) patients were treated with TNF inhibitors (TNFi), while two (6.7%) underwent hematopoietic stem cell transplantation (HSCT). They all achieved clinical remission. A total of thirty-nine ADA2 causative variants were identified, six of which were novel. CONCLUSION: To establish early diagnosis and improve clinical outcomes, genetic screening and/or testing of ADA2 enzymatic activity should be performed in patients with suspected clinical features. TNFi is considered as first line treatment for those with vascular phenotypes. HSCT may be beneficial for those with hematological disease or in those who are refractory to TNFi.

Anti-nuclear matrix protein 2+ juvenile dermatomyositis with severe skin ulcer and infection: A case report and literature review.

BACKGROUND: Juvenile dermatomyositis (JDM) is an idiopathic inflammatory myopathy that occurs in childhood. It is characterized by muscle weakness and a characteristic rash. Previous literature reports have rarely described JDM with severe skin ulcers and infections. CASE SUMMARY: Herein, we describe a case of a 2-year-old female patient who suffered from JDM, whose myositis-specific autoantibodies were positive for anti-nuclear matrix protein 2 antibody, with progressively worsening skin ulcers and severe infections. The patient was treated with glucocorticoids and various immunosuppressants. Nevertheless, further progression of the disease and the combination of primary disease and severe infection in the later period were fatal. CONCLUSION: In children, anti-nuclear matrix protein 2+ JDM combined with skin ulcers often indicates severe disease. In such cases, personalized treatment for the primary disease and infection prevention and control are essential.

Encapsulation of a Desmodium intortum Protein Isolate Pickering Emulsion of ß-Carotene: Stability, Bioaccesibility and Cytotoxicity.

Owing to their excellent characteristics, Pickering emulsions have been widely used in the development and the application of new carriers for embedding and for delivering active compounds. In this study, ß-carotene was successfully encapsulated in a Pickering emulsion stabilized using Desmodium intortum protein isolate (DIPI). The results showed that the encapsulation efficiencies of ß-carotene in the control group Tween 20 emulsion (TE) and the DIPI Pickering emulsion (DIPIPE) were 46.7 ± 2.5% and 97.3 ± 0.8%, respectively. After storage for 30 days at 25 °C and 37 °C in a dark environment, approximately 79.4% and 72.1% of ß-carotene in DIPIPE were retained. Compared with TE, DIPIPE can improve the stability of ß-carotene during storage. In vitro digestion experiments showed that the bioaccessibility rate of ß-carotene in DIPIPE was less than that in TE. Cytotoxicity experiments showed that DIPI and ß-carotene micelles within a specific concentration range exerted no toxic effects on 3T3 cells. These results indicate that DIPIPE can be used as a good food-grade carrier for embedding and transporting active substances to broaden the application of the protein-based Pickering emulsion system in the development of functional foods.

Association between high mobility group box 1 protein and juvenile idiopathic arthritis: a prospective longitudinal study.

OBJECTIVE: To analyze the levels of high mobility group box 1 (HMGB1) protein on different courses of juvenile idiopathic arthritis (JIA). METHODS: In our prospective longitudinal study, children with JIA were included with their blood samples collected at the first visit, 1-month, 3-month, and 6-month follow-up, respectively. Samples were also collected from healthy controls and children with reactive arthritis at the first visit. Levels of HMGB1 were determined using enzyme-linked immunosorbent assays. Clinical disease characteristics and routine laboratory findings were analyzed as well. RESULTS: A total of 64 children were enrolled, of whom 31 (48.4%) were female. The median age at the first visit for participants with JIA was 9.25 years (range, 1.42-15.42) and the median duration of disease was 2.38 months (range, 1.53-49.31). Serum HMGB1 levels at the first visit were significantly elevated in children with systemic JIA compared with other groups, and so were in enthesitis-related arthritis versus healthy controls. Significant correlations were established at the first visit between HMGB1 levels and duration of disease, C-reactive protein, percentage of neutrophils, and ferritin. Data from all samples revealed that serum HMGB1 levels in JIA were significantly associated with erythrocyte sedimentation rates, C-reactive protein, percentage of neutrophils, and disease activity scores. CONCLUSIONS: Serum HMGB1 may be associated with clinical disease activity of JIA and specifically increased at the first visit in children with systemic JIA, suggesting its function as a sensitive inflammatory marker. Further large-scale studies are warranted to explore its spectrum in JIA.

Comparative Efficacy and Safety of Non-Steroidal Anti-Inflammatory Drugs in Patients With Juvenile Idiopathic Arthritis: A Systematic Review and Network Meta-analysis.

OBJECTIVE: We conducted a systematic review and network meta-analysis to compare the efficacy and safety of nine non-steroidal anti-inflammatory drugs (NSAIDs) in treating patients with juvenile idiopathic arthritis (JIA). METHODS: Randomized controlled trials (RCTs) of NSAIDs for the treatment in children with JIA were searched systematically by using MEDLINE, EMBASE, and the Cochrane Library for available literature up to January 1, 2019. Bayesian network meta-analysis was used to combine direct and indirect evidence on treatment effectiveness and safety. RESULTS: Eight eligible RCTs involving 1112 patients with JIA were identified, addressing 9 interventions. The ranking probability plot based on the surface under the cumulative ranking curve (SUCRA) indicated that celecoxib (6 mg/kg twice-a-day) had the highest probability of being most effective (SUCRA = 76.4%) among four NSAIDs (celecoxib, rofecoxib, meloxicam, and naproxen). Also, rofecoxib (0.3 mg/kg once-a-day) and piroxicam demonstrated a higher probability of safety in treating children with JIA (SUCRA = 33.0% and 35.5%, respectively), compared with other interventions. CONCLUSIONS: The quality of available evidence limits the formation of powerful conclusions regarding the comparative efficacy or safety of NSAIDs used to treat JIA.

Cytochrome C Oxidase Assembly Factor 1 Homolog Predicts Poor Prognosis and Promotes Cell Proliferation in Colorectal Cancer by Regulating PI3K/AKT Signaling.

PURPOSE: Colorectal cancer (CRC) is one of the most common malignancies in the world. The prognosis of advanced CRC is still poor. The purpose of this study was to identify a gene expression profile associated with CRC that may contribute to the early diagnosis of CRC and improve patient prognosis. PATIENTS AND METHODS: Five pairs of CRC tissues and paracancerous tissues were used to identify causative genes using microarray assays. The prognostic value of Cytochrome C Oxidase Assembly Factor 1 Homolog (COA1) in CRC was assessed in 90 CRC patients. Loss-of-function assays, cell proliferation assays using Celigo and MTT, colony formation assays, a subcutaneous xenograft mouse model, and apoptosis assays were used to define the effects of downregulation of COA1 in CRC cells in vitro and in vivo. The underlying molecular mechanisms of COA1 in CRC were also investigated. RESULTS: The causative gene COA1 was identified through microarray analysis. COA1 expression in CRC was notably associated with pathologic differentiation, tumor size, and tumor depth. COA1 expression may act as an independent prognostic factor for overall survival of CRC. Knockdown of COA1 inhibited the proliferation of CRC cells in vitro and the tumorigenicity of CRC cells in vivo. Decreased COA1 expression induced apoptosis of CRC cells. Based on the microarray assay results comparing HCT116 cells transfected with lentivirus encoding anti-COA1 shRNA or negative control shRNA, ingenuity pathway analysis (IPA) revealed that the PI3K/AKT signaling pathway was significantly enriched. Moreover, CCND1, mTOR, AKT1, and MDM2 were identified as the downstream genes of COA1. CONCLUSION: These findings demonstrate that COA1 promotes CRC cell proliferation and inhibits apoptosis by regulating the PI3K/AKT signaling pathway. Our results implicate COA1 as a potential oncogene involved in tumor growth and progression of CRC.

Application for proteomics analysis technology in studying animal-derived traditional Chinese medicine: A review.

Different therapeutically active ingredients, from plants, animals, and mineral sources, are prescribed as traditional Chinese medicines (TCM). TCMs, from animal sources, are rich in proteins and peptides. Different advanced proteomics technologies, such as two-dimensional gel electrophoresis (2-DE), multi-dimensional liquid chromatography (MDLC), matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF-MS), and isobaric tags for relative and absolute quantitation (iTRAQ), have been applied to analyze TCMs, from animal sources. This paper reviews the common proteomic techniques for analyzing animal - derived TCMs. Various scientific studies have reported the application of proteomics for locating drug targets, identifying active components, and elucidating the mechanisms of action of animal - derived TCMs. However, these researches are still at the preliminary stage. This review has also discussed the existing challenges and future directions in this field of research.

Blood Pressure Variability during Angiography in Patients with Ischemic Stroke and Intracranial Artery Stenosis.

Our aim was to investigate factors predicting blood pressure (BP) variability during diagnostic cerebral angiography and associations between BP variability and clinical outcomes in patients with acute and subacute ischemic stroke and intracranial artery stenosis. 114 patients with ischemic stroke and intracranial artery stenosis (stenosis rate >50%) were recruited. Patients who underwent cerebral angiography within 3 days and 3-14 days of disease onset are referred to be Group A and Group S, respectively. BP variability in Group A was defined as the coefficient of variance (CV) of BP. Univariate and multivariate regression analyses were used to identify predictors of CV of BP and associations between CV of BP and clinical outcomes at discharge. In Group A patients, advanced age was associated with increased CV of SBP and diastolic blood pressure (DBP), and antihypertensive use was associated with lower CV of SBP. Male was associated with lower CV of DBP. In Group S, higher CV of SBP was associated with hypertension and antihypertensive use. Males had lower CV of SBP than females. The calcium channel blocker was associated with lower CV of DBP. Higher scores of the Stroke Scale at admission were significantly associated with poor clinical outcomes for both groups, while BP variability was not. Factors associated with BP variability are significantly different between stroke patients undergoing angiography within 3 days vs. 3-14 days after disease onset. BP variability is not significantly associated with clinical outcomes at discharge.

Synthesis and evaluation of novel peptidomimetics bearing p-aminobenzoic acid moiety as potential antidiabetic agents.

Aim: Search for a new class of potential antidiabetic agents. Methodology: A series of novel peptidomimetics bearing the p-aminobenzoic acid moiety (TM3-TM6) were designed and synthesized. For all synthetic target molecules, the peroxisome proliferator response element (PPRE) activated activities have been evaluated and the toxicity were computed. Results & discussion: 46 new p-aminobenzoic acid derivatives have been characterized by 1H NMR, 13C NMR and high-resolution mass spectrometry (HRMS). The results of in vitro PPRE-activated activity, molecular docking study and toxicity prediction revealed that these compounds had potential antidiabetic activities and low toxicity. In particular compound 3b had up to 87% PPRE-activated activity compared with pioglitazone. This discovery may provide new insights for finding novel PPRE lead compound.

Infliximab therapy and outcomes in patients with polyarticular juvenile idiopathic arthritis: a single-center study in China.

BACKGROUND: Juvenile idiopathic arthritis (JIA) is a chronic inflammatory disease that includes seven heterogeneous subgroups with different prognoses. In particular, polyarticular JIA (pJIA) has a longer period of active disease and a poorer prognosis. Tumor necrosis factor (TNF)-alpha inhibitors are effective in patients with pJIA, but the therapeutic regimen remains controversial. Here, we performed a single-center study to determine the potential correlation between TNF-alpha inhibitor (infliximab) therapy and outcomes in these patients. METHODS: Clinical data of 40 pJIA patients were collected at our center from January 1, 2010 to January 1, 2018, and patients were grouped according to the timing of infliximab therapy. The erythrocyte sedimentation rate (ESR), the number of joints with active disease, and the 27-point juvenile arthritis disease activity score (JADAS-27) were analyzed. RESULTS: The ESR, the active joint count, and the JADAS-27 decreased significantly in all groups after 3 months (P = 0.041/0.415/0.008, 0.022/0.030/ < 0.001, and 0.05/0.012/ < 0.001, respectively) and 6 months (P = 0.036/0.045/0.041, 0.076/0.037/ < 0.001, and 0.096/0.006/ < 0.001, respectively) of infliximab treatment, although the rates of change of these parameters were similar. However, after 12 months, only patients treated with infliximab within 3 months of disease onset had a stable ESR, active joint count, and JADAS-27, while these parameters increased sharply when infliximab was administered 3 months and especially 1 year after disease onset. CONCLUSIONS: TNF-alpha is a pleiotropic pro-inflammatory cytokine of crucial importance in the pathogenesis of JIA. Infliximab can improve the outcomes of patients with pJIA significantly, and should be introduced early during the clinical course.

Two paternal mosaicism of mutation in ELANE causing severe congenital neutropenia exhibit normal neutrophil morphology and ROS production.

Severe congenital neutropenia caused by ELANE gene mutation is a rare disease. To date, only four families were reported with mosaicism. Here we examined the morphology and function of granulocytes isolated from two patients and their mosaic fathers. Analysis of granulocytes isolated from the fathers revealed no genetic mutations. DNA extracted from fractionated peripheral blood mononuclear cells (PBMCs) and fingernails obtained from both fathers did harbor the mutation, suggesting mosaicism. Granulocytes isolated from the patients displayed significantly weaker ionomycin-induced intracellular reactive oxygen species (ROS) responses than those isolated from the fathers. Both patients showed increased expression of neutrophil elastase, whereas the mosaic fathers showed normal expression. Taken together, the results suggest that granulocytes from these SCN patients are immunocompromised, whereas those from the mosaic fathers are normal. These findings may provide new insight into disease diagnosis, prognosis, therapy and genetic counseling.

[Microbial community diversity and its characteristics in Magnolia Officinalis Cortex "sweating" process based on high-throughput sequencing].

Magnolia Officinalis Cortex has been used as a traditional Chinese herb for thousands of years in China. According to Chinese Pharmacopoeia,the processing of Magnolia Officinalis Cortex needs " sweating" or " Fahan",which was a special drying process and considered to be an important symbol for high quality and genuine medicinal materials. In this unique processing mode,Magnolia Officinalis Cortex's microbial community structure may be changed,but little is known about microbial diversity during the " sweating". In this study,to analyze the change and its change rules of microbial community of Magnolia Officinalis Cortex in the whole process of " sweating",and find out the microbial community that affects the quality of Magnolia Officinalis Cortex in the process of its " sweating",and provide a basis for further research on the microbial transformation of Magnolia Officinalis Cortex,MiSeq highthroughput sequencing was used to evaluate the microbial diversity of natural " sweating" of Magnolia Officinalis Cortex. In this research,334 genera fungi and 674 genera bacteria were identified. The dominant species weren' t obvious during the early stage of " sweating". Candida was the dominant fungal species( 45. 01%-71. 93%) during the medium " sweating" stage. Aspergillus is the dominant fungal species( 45. 83%-95. 51%) during the late stage of " sweating". Moreover,Enterobacter and Klebsiella were the primary bacterial genus( ≥56. 05%) during the middle and late stages of " sweating". In addition,the predominant bacteria in the process of " sweating" included Bacillus,Deinococcus,Sphingomonas,Hymenobacter and Jatrophihabitans. In conclusion,the microbial diversities and the main dominant fungi and bacteria in the process of " sweating" of Magnolia Officinalis Cortex were initially determined. It was also found that the metabolism of Aspergillus and Candida may be related to the character formation,which were sweet odor and brown inner surface after " sweating". The results provide a theoretical basis for the study of the influence of different microorganisms on the excellent traits formation of " sweating" Magnolia Officinalis Cortex.

Relationship between intracranial internal carotid artery calcification and enlarged cerebral perivascular space.

PURPOSE: The association between intracranial internal carotid artery (IICA) calcification and lacunes, white matter hyperintensity (WMH), and cerebral microbleeds (CMBs) has been well researched. However, enlarged cerebral perivascular space (PVS) has not yet been reported to correlate with intracranial internal carotid artery calcification. Therefore, the primary aim of this study was to investigate the relationship between IICA calcification and enlarged PVS. METHODS: A total of 189 patients with ischemic stroke in the middle cerebral artery territory who presented within 7 days of ictus from 2012 to 2015 were enrolled respectively. All patients were required to have undergone head computed tomography, magnetic resonance imaging, susceptibility-weighted magnetic resonance imaging, magnetic resonance angiography, or computed tomography angiography. Clinical characteristics were recorded. IICA calcification and enlarged PVS were semi-quantitatively evaluated, and the presence of lacunes, WMH, and CMBs was recorded. RESULTS: Of the 189 patients, 63.5% were male. Mean age of the patients was 68.6 ± 12.2 years. There were 104 patients with IICA calcification. Age, diabetes mellitus, lacunes, and white matter hyperintensity were significantly associated with IICA calcification (P < 0.05). Multivariate logistic regression analysis showed that age, diabetes mellitus, and lacunes were independent predictors of IICA calcification (P < 0.05). A lower risk of IICA calcification was found in patients with a higher enlarged PVS score (P = 0.004). CONCLUSION: Higher enlarged PVS scores were associated with a lesser degree of IICA calcification. There appears to be a relationship between reduced risk of IICA calcification and enlarged PVS.

Novel compound heterozygous mutations in ZAP70 in a Chinese patient with leaky severe combined immunodeficiency disorder.

In humans, the complete lack of tyrosine kinase ZAP70 function results in combined immunodeficiency (CID), with abnormal thymic development and defective T cell receptor (TCR) signaling of peripheral T cells, characterized by the selective absence of CD8+ T cells. So far, 15 unique ZAP70 mutations have been identified in approximately 20 patients with CID, with variable clinical presentations. Herein, we report the first case from China of novel compound heterozygous mutations in ZAP70 (c.598-599delCT, p.L200fsX28; c.847 C>T, R283H). The patient suffered from early-onset and recurrent infections, but showed normal growth and development without signs of failure to thrive, thus presenting as leaky SCID. The patient also had clinical manifestations of autoimmunity, such as eczematous skin lesion, inflammatory bowel disease (IBD), and intractable diarrhea, suggesting compromised T cell tolerogenic functions. Residual ZAP70 expression was identified. Immunological analysis revealed the selective absence of CD8+ T cells in the periphery and the presence of CD4+ T cells that failed to respond to phytohemagglutinin. Stimulation with lectin from pokeweed mitogen also failed to stimulate B cell proliferation in the patient. The frequency of Tfhs and Tregs in the patient was lower compared with the normal reference. Compared with the age-matched healthy control, the level of IL-17 was higher and the levels of IFN-γ, IL-4, and IL-21 were lower. Infants with selected CD8 deficiency and severe autoimmune disorders or exaggerated inflammation should be screened for ZAP70 deficiency.

The clinical features of autoimmunity in 53 patients with Wiskott-Aldrich syndrome in China: a single-center study.

UNLABELLED: Autoimmune disease (AD) is common in patients with Wiskott-Aldrich syndrome (WAS) and patients with WAS who has an AD usually constitute a high-risk group with poor outcome. However, knowledge of AD in WAS is limited in China. In this study, medical records of 53 patients with WAS at Children´s Hospital of Chongqing Medical University from April 2004 to January 2014 were evaluated retrospectively and 14 patients (26%) had at least one AD. Autoimmune hemolytic anemia (AIHA) was the most common and detected in 12 patients (23%), other complications included immune thrombocytopenia (n = 1), immune neutropenia (n = 1), autoimmune arthritis (n = 1), and renal injury (n = 1). No significant differences were found in the level of serum immunoglobulins and lymphocyte subsets between the AD group and non-AD group. Although eight patients with AD received hematopoietic stem cell transplantation (HSCT), three patients died of pulmonary infection after HSCT. CONCLUSIONS: AD is frequent in Chinese patients with WAS and AIHA was the most common. AD is a poor prognosis factor for WAS and should be treated as early as possible by HSCT. WHAT IS KNOWN: • Autoimmune disease is common in patients with WAS. • Manifestations, follow-up finding, and treatment approaches of autoimmune disease in Chinese patients with WAS have received less attention in the literature. What is New: • This study is firstly intended for evaluation of the clinical and immune characteristics of autoimmune disease in a large series Chinese patients with WAS. • AD is frequent in Chinese patients with WAS and AIHA is the most common.

In vivo reversion of an inherited mutation in a Chinese patient with Wiskott-Aldrich syndrome.

A spontaneous reversion that restores Wiskott-Aldrich syndrome protein (WASP) expression was reported recently. However, the genetic mechanism underlying the reversion event was unclear. In the present study, a WAS patient with a nonsense mutation (155 C>T, R41X) was followed during a three-year period. No expression of WASP was detected in peripheral blood mononucleated cells (PBMCs) in 2009 and a small population of intracellular WASP positive lymphocytes was detected during the following three years. The increasing trend of the revertant genotype was significant. WASP-expressing cells were present mainly CD56+ NK cells and CD8+ T cells. Sorted WASP+ cells were analyzed, indicating that the population of CD3+ T cells increased from 36.81% to 99.8%. Although the revertant cells in vivo may have a growth advantage, the patient presented a persistent autoimmune disease, thrombocytopenia, and died from extensive pulmonary fibrosis. The results suggest that the clinical consequences of T-cell mosaicism in WAS remain difficult to predict and is not sufficient to fully normalize immune functions in patients with WAS.

Clinical characteristics of severe congenital neutropenia caused by novel ELANE gene mutations.

BACKGROUND: Mutations within the ELANE gene, which encodes human neutrophil elastase, are the most common genetic causes of severe congenital neutropenia (SCN). No cases of SCN have been previously described from a Chinese population. Herein, we describe the clinical, hematologic and molecular characteristics of 7 Chinese SCN cases with novel ELANE mutations. METHODS: Seven Chinese pediatric patients (4 males and 3 females) with suspected SCN were enrolled in this study. Clinical data, peripheral blood, bone marrow and immune function were evaluated for SCN. ELANE genomic DNA and cDNA sequences from patients and potential carriers were analyzed using polymerase chain reaction (PCR) and direct sequencing. RESULTS: All the7 patients experienced recurrent infection (soft tissue, lung, oral cavity) during a period of 120 days. Noninfectious conditions such as anemia and osteopenia were found in most patients, and absolute peripheral neutrophil counts varied. DNA and cDNA sequencing demonstrated that the patients harbored a range of heterozygous ELANE gene mutations, including substitution, deletion, insertion and frame shift alterations. All the mutations had not been reported previously; however, no mutation carriers were identified among the parents or siblings, even in a family with 2 affected offspring. CONCLUSION: SCN cases were identified for the first time in China, and all patients carried novel ELANE mutations. Granulocyte-colony stimulating factor (G-CSF) was an effective treatment for most of the SCN patients and prevented life-threatening bacterial infections.