scholarly journals The clinical, immunological and genetic features of 12 Chinese patients with STAT3 mutations

2020 ◽  
Vol 16 (1) ◽  
Author(s):  
Li Lin ◽  
Ying Wang ◽  
Bijun Sun ◽  
Luyao Liu ◽  
Wenjing Ying ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Clinical Symptoms ◽  
Current Knowledge ◽  
Elevated Serum ◽  
Age At Diagnosis ◽  
Chinese Patients ◽  
Common Mutation ◽  
Novel Mutations ◽  
Mutation Site ◽  
Stat3 Mutations

Abstract Background Loss-of-function (LOF) mutations in signal transducer and activator of transcription 3 (STAT3) is one of the causes of STAT3 hyperimmunoglobulin E (IgE) syndrome (STAT3-HIES), while gain-of-function (GOF) mutations in STAT3 lead to immune dysregulation diseases. We retrospectively analyzed the age, common clinical symptoms, immunologic and molecular manifestations in 11 patients with LOF STAT3 mutations and 1 patient with a GOF STAT3 mutation. Methods Twelve patients were enrolled in our study. Serum immunoglobulin measurements, lymphocyte subset detection and whole-exome sequencing were performed. Results The median age at diagnosis of STAT3-HIES patients was 4.74 years. Eczema, recurrent respiratory infections, fevers, abscesses and Staphylococcus aureus infections were the classic manifestations. Elevated serum IgE levels are not always observed in conjunction with high eosinophil counts. A moderate viral DNA load was also measured in peripheral blood mononuclear cells. We noticed that c. 1144C>T was the most common mutation site, followed by c.1311C>A. Additionally, c.1311C>A and c. 1826G>C are two novel mutations. Eight patients achieved notable improvement after receiving intravenous immunoglobulin. Conclusion We updated the current knowledge of this topic. We found an earlier median age at diagnosis, a higher survival rate, and a general lack of nonimmunological abnormalities; we also described the treatment details and novel mutations involve in STAT3-HIES and compared STAT3 LOF and GOF mutations.

scholarly journals The clinical, immunological and genetic features of 12 Chinese patients with STAT3 mutations

2020 ◽  
Author(s):  
Li Lin ◽  
Ying Wang ◽  
Bijun Sun ◽  
Luyao Liu ◽  
Wenjing Ying ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Clinical Symptoms ◽  
Current Knowledge ◽  
Elevated Serum ◽  
Age At Diagnosis ◽  
Chinese Patients ◽  
Common Mutation ◽  
Novel Mutations ◽  
Mutation Site ◽  
Stat3 Mutations

Abstract Background: Loss-of-function (LOF) mutations in signal transducer and activator of transcription 3 (STAT3) is one of the causes of STAT3 hyperimmunoglobulin E (IgE) syndrome (STAT3-HIES), while gain-of-function (GOF) mutations in STAT3 lead to immune dysregulation diseases. We retrospectively analyzed the age, common clinical symptoms, immunologic and molecular manifestations in 11 patients with LOF STAT3 mutations and 1 patient with a GOF STAT3 mutation.Methods: Twelve patients were enrolled in our study. Serum immunoglobulin measurements, lymphocyte subset detection and whole-exome sequencing were performed.Results: The median age at diagnosis of STAT3-HIES patients was 4.74 years. Eczema, recurrent respiratory infections, fevers, abscesses and Staphylococcus aureus infections were the classic manifestations. Elevated serum IgE levels are not always observed in conjunction with high eosinophil counts. A moderate viral DNA load was also measured in peripheral blood mononuclear cells. We noticed that c. 1144C>T was the most common mutation site, followed by c.1311C>A. Additionally, c.1311C>A and c. 1826G>C are two novel mutations. Eight patients achieved notable improvement after receiving intravenous immunoglobulin. Conclusion: We updated the current knowledge of this topic. We found an earlier median age at diagnosis, a higher survival rate, and a general lack of nonimmunological abnormalities; we also described the treatment details and novel mutations involve in STAT3-HIES and compared STAT3 LOF and GOF mutations.

scholarly journals The clinical, immunological and genetic features of 12 Chinese patients with STAT3 mutations

2020 ◽  
Author(s):  
Li Lin ◽  
Ying Wang ◽  
Bijun Sun ◽  
Luyao Liu ◽  
Wenjing Ying ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Clinical Symptoms ◽  
Current Knowledge ◽  
Elevated Serum ◽  
Age At Diagnosis ◽  
Chinese Patients ◽  
Common Mutation ◽  
Novel Mutations ◽  
Mutation Site ◽  
Stat3 Mutations

Abstract Background: Loss-of-function (LOF) mutations in signal transducer and activator of transcription 3 (STAT3) is one of the causes of STAT3 hyperimmunoglobulin E (IgE) syndrome (STAT3-HIES), while gain-of-function (GOF) mutations in STAT3 lead to immune dysregulation diseases. We retrospectively analyzed the age, common clinical symptoms, immunologic and molecular manifestations in 11 patients with LOF STAT3 mutations and 1 patient with a GOF STAT3 mutation.Methods: Twelve patients were enrolled in our study. Serum immunoglobulin measurements, lymphocyte subset detection and whole-exome sequencing were performed.Results: The median age at diagnosis of STAT3-HIES patients was 4.74 years. Eczema, recurrent respiratory infections, fevers, abscesses and Staphylococcus aureus infections were the classic manifestations. Elevated serum IgE levels are not always observed in conjunction with high eosinophil counts. A moderate viral DNA load was also measured in peripheral blood mononuclear cells. We noticed that c. 1144C>T was the most common mutation site, followed by c.1311C>A. Additionally, c.1311C>A and c. 1826G>C are two novel mutations. Eight patients achieved notable improvement after receiving intravenous immunoglobulin. Conclusion: We updated the current knowledge of this topic. We found an earlier median age at diagnosis, a higher survival rate, and a general lack of nonimmunological abnormalities; we also described the treatment details and novel mutations involve in STAT3-HIES and compared STAT3 LOF and GOF mutations.

scholarly journals The clinical, immunological and genetic features of 12 Chinese patients with STAT3 mutation

2020 ◽  
Author(s):  
Li Lin ◽  
Ying Wang ◽  
Bijun Sun ◽  
Luyao Liu ◽  
Wenjing Ying ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Immunoglobulin E ◽  
Clinical Symptoms ◽  
Elevated Serum ◽  
Chinese Patients ◽  
Onset Age ◽  
Loss Of Function ◽  
Peripheral Blood Mononuclear ◽  
Whole Exome ◽  
Genetic Features

Abstract Background: Loss-of-function (LOF) mutation in signal transducer and activator of transcription 3 (STAT3) was one of the causes of the hyper immunoglobulin E (IgE) syndrome (HIES), while gain-of-function mutation (GOF) in STAT3 leads to immune dysregulation diseases. We retrospectively report 11 LOF STAT3 patients and 1 GOF STAT3 patient and illustrate their onset age, common clinical symptoms, immunologic and molecular manifestation. Methods: 12 patients were enrolled in our study. Serum immunoglobulins, lymphocyte subset detection and whole-exome sequencing were performed. Results: The median onset age of STAT3-deficient patients was 1.89 years. Eczema, recurrent respiratory infection, apparent fever, abscesses and Staphylococcus aureus infection was the classical manifestation. Elevated serum IgE level is not entirely unanimous with high eosinophils counts. Moderate viral DNA was also measured in peripheral blood mononuclear cells. We noticed that c. 1144C>T was the most common spot, followed by c.1311C>A. Additionally, c.1311C>A and c. 1826G>C are two novel mutations. Eight patients obtained a notable improvement after received intravenous immunoglobulin (IVIG). Conclusion: We believe IVIG may help reduce the opportunity of infection in STAT3-deficient patients. Significant variance at onset age probably is a great challenge for clinicians and urgently needs early diagnosis and treatment.

scholarly journals Identification and Clinical Characteristics Analysis of HNF-1A Mutations p.I27L, p.S487N and p.G574S in Chinese Patients with MODY3

2021 ◽  
Author(s):  
Rong Long ◽  
Chen-Xi Yu ◽  
Hui-Jun Yang ◽  
Tai-Cheng Zhou ◽  
Lei Yang ◽  
...  
Keyword(s):  
Plasma Glucose ◽  
Clinical Characteristics ◽  
Clinical Symptoms ◽  
Glycosylated Hemoglobin ◽  
Chinese Patients ◽  
Islet Function ◽  
Onset Age ◽  
Maturity Onset Diabetes ◽  
Mutation Site ◽  
Onset Diabetes

Abstract Background: Due to the rarity, the type 3 of maturity-onset diabetes of the young (MODY3) has not been explored comprehensively. The study aimed to describe and analyze the molecular and clinical characteristics of MODY3, which could help physicians understand the subtype of diabetes and increase the diagnosis rates in the future.Methods: Ten unrelated patients with suspected maturity-onset diabetes of the young (MODY) were included in the study based on information on family history and onset age. Sanger sequencing was used to identify cases with mutations in the hepatic nuclear factor 1A gene (HNF-1A). Results: Five patients were identified with MODY3, three cases (60%) with p.I27L mutation, one case (20%) with p.S487N mutation, and one case (20%) with p.G574S mutation. The average onset age was (23.00±3.00) years and the average age of diagnosis was (28.67±9.29) years. Most patients had typical clinical symptoms (polydipsia, polyuria, polyphagia, and weight loss). The main complications included diabetic ketoacidosis (DKA, 3/5,60%), diabetic macroangiopathy (2/5,40%), diabetic peripheral neuropathy (DPN,3/5,60%), diabetic nephropathy (DN,1/5,20%) and diabetic retinopathy (DR,1/5,20%). Four patients (80%) had fatty liver. The average body mass index (BMI) (26.39±4.67) kg/㎡, triglyceride (TG 2.95±1.43 mmol/L) and low-density lipoprotein (LDL-C 3.37±0.65 mmol/L) were beyond normal value. The glycosylated hemoglobin A1c (HbA1c 12.45±4.60 %), fasting plasma glucose (FPG 10.10±3.57 mmol/L) and postprandial plasma glucose (PPG 21.88±2.53 mmol/L) also increased dramatically. In addition, islet function examination revealed impaired secretion and slightly poor reserve function, which was similar to the changes inT2DM. All five patients used insulin, three (60%) also using antidiabetic drugs which did not include sulfonylureas.Conclusions: In brief, five patients were identified with MODY3. The mutation site could influence the onset age, the islet function and the incidence of complications. The age at diagnosis was 4.2 years later than the onset age. The control of diabetes was poor due to the inappropriate treatment. It is vital to make an early diagnosis and provide appropriate treatment for MODY3 patients.

Hepatitis G Viral RNA in Serum and in Peripheral Blood Mononuclear Cells and Its Relation to HCV-RNA in Patients with Clotting Disorders

1997 ◽  
Vol 77 (05) ◽  
pp. 0868-0872 ◽  
Author(s):  
Li Sheng ◽  
Ann Soumillion ◽  
Kathelijne Peerlinck ◽  
Chris Verslype ◽  
Lan Lin ◽  
...  
Keyword(s):  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Elevated Serum ◽  
Normal Serum ◽  
Hcv Rna ◽  
Peripheral Blood Mononuclear ◽  
Hepatitis G Virus ◽  
Blood Mononuclear Cells ◽  
Hepatitis G

SummaryThe hepatitis G virus (HGV) has recently been identified as a new member of the Flaviviridae family. Infection by this virus is thought to be associated with blood borne hepatitis. In this study, the presence of HCV- and HGV-RNAs in serum or plasma (175 patients) and in peripheral blood mononuclear cells (PBMC) (133 patients) was investigated in patients with clotting disorders using a sensitive reverse transcriptase polymerase chain reaction (RT-PCR). HGV-RNA was detected in serum of 26 patients (14.8%). In apparently healthy blood donors, serum HGV-RNA was detected in 4 of 358 individuals investigated (1.12%). Ninety two percent of the 26 serum HGV-RNA positive patients had coinfection with the hepatitis C virus (HGV), especially with HCV genotype lb, the most common genotype in Belgium. Of these coinfected patients, 15 (62.5%) showed elevated serum ALT levels. Two patients who were solely infected with HGV had normal serum ALT. HGV-RNA in PBMC was found in 18 patients, of whom 3 were negative for serum HGV-RNA. As in case of HCV, HGV-RNA in PBMC is preferentially sensitive to interferon treatment. Nevertheless, rapid reappearance of HGV-RNA in PBMC was observed after cessation of treatment. In one patient, persistent serum ALT elevation seems to be associated with continued HGV viremia, despite the disappearance of serum HCV-RNA.

scholarly journals Chronic Wasting Due to Liver and Rumen Flukes in Sheep

Animals ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 549
Author(s):  
Alexandra Kahl ◽  
Georg von Samson-Himmelstjerna ◽  
Jürgen Krücken ◽  
Martin Ganter
Keyword(s):  
Fasciola Hepatica ◽  
Clinical Symptoms ◽  
Current Knowledge ◽  
Infection Intensity ◽  
Liver Parenchyma ◽  
Trematode Species ◽  
Helminth Infections ◽  
Juvenile Worm ◽  
Juvenile Stages ◽  
Common Liver Fluke

Grazing sheep and goats are constantly exposed to helminth infections in many parts of the world, including several trematode species that causes a range of clinical diseases. The clinical picture of flukes is dependent upon the organs in which they develop and the tissues they damage within the respective organs. Accordingly, infections with the common liver fluke Fasciola hepatica, which, as juvenile worm migrates through the liver parenchyma for several weeks, may be associated with hepatic disorders such as impairment of carbohydrate, protein and fat metabolism, followed by chronic wasting. In contrast, the lancet fluke Dicrocoelium dendriticum, which does not exhibit tissue migration and thus does not lead to major tissue damage and bleeding, also does not lead to significant clinical symptoms. Rumen flukes such as Cotylophoron daubneyi cause catarrhal inflammation during their migration through the intestinal and abomasal epithelium during its juvenile stages. Depending on the infection intensity this may result in a range of clinical symptoms including diarrhoea, inappetence or emaciation. In this review, we aim to provide an update on the current knowledge on flukes particularly concerning the clinical relevance of the most important fluke species in sheep.

scholarly journals Development of revised diagnostic criteria for Fuchs’ uveitis syndrome in a Chinese population

2021 ◽  
pp. bjophthalmol-2021-319343
Author(s):  
Peizeng Yang ◽  
Wanyun Zhang ◽  
Zhijun Chen ◽  
Han Zhang ◽  
Guannan Su ◽  
...  
Keyword(s):  
Diagnostic Criteria ◽  
Clinical Symptoms ◽  
Southern China ◽  
High Sensitivity ◽  
Northern China ◽  
Chinese Patients ◽  
Tertiary Referral Centre ◽  
Tree Algorithms ◽  
Vitreous Opacities ◽  
Fuchs Uveitis Syndrome

Background/aimsFuchs’ uveitis syndrome (FUS) is one of the frequently misdiagnosed uveitis entities, which is partly due to the absence of internationally recognised diagnostic criteria. This study was performed to develop and evaluate a set of revised diagnostic criteria for FUS.MethodsThe clinical data of Chinese patients with FUS and patients with non-FUS were collected and analysed from a tertiary referral centre between April 2008 and December 2020. A total of 593 patients with FUS and 625 patients with non-FUS from northern China were enrolled for the development of diagnostic criteria for FUS. Three hundred and seventy-seven patients with FUS and 503 patients with non-FUS from southern China were used to validate the criteria. Clinical symptoms and ocular signs were collected from all patients with FUS and patients with non-FUS. Multivariate two-step cluster analysis, logistic regression and decision tree algorithms in combination with the clinical judgement of uveitis experts were used to revise diagnostic criteria for FUS.ResultsThree essential findings including diffuse iris depigmentation, absence of posterior synechiae, mild inflammation in the anterior chamber at presentation and five associated findings including mostly unilateral involvement, cataract, vitreous opacities, absence of acute symptoms and characteristic iris nodules were used in the development of FUS diagnostic criteria. All essential findings were required for the diagnosis of FUS, and the diagnosis was further strengthened by the presence of associated findings.ConclusionRevised diagnostic criteria for FUS were developed and validated by analysing data from Chinese patients and showed a high sensitivity (96.55%) and specificity (97.42%).

scholarly journals Transient increase in circulating gamma/delta T cells during Plasmodium vivax malarial paroxysms.

1994 ◽  
Vol 179 (1) ◽  
pp. 311-315 ◽  
Author(s):  
M K Perera ◽  
R Carter ◽  
R Goonewardene ◽  
K N Mendis
Keyword(s):  
T Cells ◽  
Plasmodium Vivax ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Clinical Symptoms ◽  
Gastrointestinal Symptoms ◽  
Gamma Delta T Cells ◽  
Gamma Delta ◽  
Endemic Region ◽  
Gastrointestinal Pathology

The percentage of peripheral blood mononuclear cells (PBMC) bearing the CD3+ phenotype and the alpha/beta and gamma/delta T cell receptors (TCR) in PBMC were examined in Plasmodium vivax malaria patients and convalescents. The cells were labeled with monoclonal antibodies, stained with either fluorescence or phycoerythrin, and examined by ultraviolet (UV) microscopy. A highly significant increase in both the proportion and the absolute numbers of gamma/delta T cells (p < 0.005 and < 0.001, respectively, Student's t test) was observed in nonimmune P. vivax patients during clinical paroxysms compared to nonmalarial controls. These T cells, which normally constitute not more than 3-5% of PBMC, constituted < or = to 30% of PBMC during paroxysms in these nonimmune patients in whom the clinical symptoms were severe. A less significant increase of gamma/delta T cells were also observed in these nonimmune patients during infection, between paroxysms and during convalescence. In contrast, in an age-matched group of semi-immune patients resident in a malaria-endemic region of the country, in whom the clinical disease was comparatively mild, there was no increase in gamma/delta T cells either during infection, even during paroxysms, or convalescence. The severity of disease symptoms in patients as measured by a clinical score correlated positively with the proportion of gamma/delta T cells in peripheral blood (r = 0.53, p < 0.01), the most significant correlation being found between the prevalence and severity of gastrointestinal symptoms, nausea, anorexia, and vomiting, and the proportion of gamma/delta T cells (r = 0.49, p = 0.002). These findings suggest that gamma/delta T cells have a role to play in the pathogenesis of malaria, possibly in the general constitutional disturbances and particularly in gastrointestinal pathology in malaria.

Detection and Functional Evaluation of −262A/T and −188A/G Polymorphisms of SLAM Gene in Patients with Systemic Lupus Erythematosus

2010 ◽  
Vol 37 (11) ◽  
pp. 2268-2272 ◽  
Author(s):  
YI YOU ◽  
ZHE WANG ◽  
GUO-HONG DENG ◽  
YI LIU ◽  
FEI HAO
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Mononuclear Cells ◽  
Gene Promoter ◽  
Chinese Patients ◽  
Luciferase Reporter ◽  
Functional Evaluation ◽  
Reporter System ◽  
Systemic Lupus ◽  
Peripheral Blood Mononuclear

Objective.Signaling lymphocytic activation molecule (SLAM) has been related to the pathology of systemic lupus erythematosus (SLE) through regulation of T cell-dependent humoral immune responses. We investigated the functional associations of the −262A/T and −188A/G polymorphisms of SLAM in Chinese patients with SLE.Methods.Genotyping of −262A/T (rs2295614) and −188A/G (rs2295613) in SLAM was carried out in 248 cases and 278 controls. Promoter activities of haplotypes on the SLAM gene were evaluated with the dual-luciferase reporter system. The mRNA expressions of SLAM on peripheral blood mononuclear cells (PBMC) of SLE patients with different genotypes were determined by real-time polymerase chain reaction.Results.Frequencies of −262A allele and −188G allele were significantly higher in SLE patients than in controls. Haplotype analysis and multifactorial logistic regression analysis showed that individuals with the AG/AG haplotype had increased susceptibility to SLE (p = 0.002, OR 1.478, 95% CI 1.152–1.897). In response to PHA stimulation, the SLAM mRNA expression on PBMC of SLE patients was significantly higher in −262A-188G haplotype homozygotes compared with −262A-188G heterozygotes and individuals with other genotypes.Conclusion.Our findings suggest that −262A-188G haplotype in the SLAM gene promoter contributes to the risk of SLE by increasing the expression of SLAM.

Increased Serum Interleukin 22 in Patients with Rheumatoid Arthritis and Correlation with Disease Activity

2012 ◽  
Vol 39 (7) ◽  
pp. 1320-1325 ◽  
Author(s):  
LAURINDO FERREIRA da ROCHA ◽  
ÂNGELA LUZIA BRANCO PINTO DUARTE ◽  
ANDRÉA TAVARES DANTAS ◽  
HENRIQUE ATAÍDE MARIZ ◽  
IVAN da ROCHA PITTA ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Mononuclear Cells ◽  
Activity Index ◽  
Elevated Serum ◽  
Serum Levels ◽  
Peripheral Blood Mononuclear ◽  
Additional Tool ◽  
Bone Erosions ◽  
Interleukin 22

Objective.To analyze the role of interleukin 22 (IL-22) in rheumatoid arthritis (RA).Methods.IL-22 serum levels were measured in 83 patients with established RA under treatment with disease-modifying antirheumatic drugs and in 30 healthy controls matched for age and sex. Patients were assessed for clinical and laboratory variables. Correlations of IL-22 serum levels with disease activity measures [Clinical Disease Activity Index (CDAI) and Disease Activity Score for 28 joints (DAS28)], serological markers, bone erosions, and demographic factors were assessed. Peripheral blood mononuclear cells (PBMC) from 30 patients with RA and 14 controls were purified and stimulatedin vitrowith phorbol myristate acetate (PMA)/ionomycin. IL-22 production by PBMC and in serum was investigated by ELISA.Results.IL-22 levels were increased in patients with RA compared with controls (mean 432.37 pg/ml and 67.45 pg/ml, respectively; p < 0.001). Levels of IL-22 correlated with DAS28 and CDAI measures. Rheumatoid factor (RF) positivity was correlated with higher levels of IL-22 in patients with RA (mean 575.08 pg/ml; p = 0.001). The presence of bone erosions was associated with high IL-22 levels (p = 0.0001). PBMC stimulated with PMA/ionomycin expressed higher levels of IL-22 in patients with RA than controls but this was not significant (mean 584.75 pg/ml and 295.57 pg/ml; p = 0.553).Conclusion.IL-22 is elevated in the serum of patients with established RA. Elevated serum IL-22 allows discrimination between patients with different clinical and laboratory measures and indicates the potential of IL-22 as an additional tool for assessment of activity in RA, particularly in patients with RF antibodies and longterm disease. IL-22 is associated with bone-destructive disease.

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