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Wen-I Lee,
Jing-Long Huang,
Kuo-Wei Yeh,
Min-Jay Yang,
Ming-Chi Lai, Li-Chen Chen,
Liang-Shiou Ou,
Tsung-Chieh Yao,
Syh-Jae Lin,
Tang-Her Jaing,
Shih-Hsiang Chen,
Meng-Ying Hsieh,
Hsin-Hui Yu,
Yin-Hsiu Chien,
Shyh-Dar Shyur
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ABSTRACT: OBJECTIVES:: Hyper IgM syndrome (HIGM), characterized by recurrent infections, low serum IgG and IgA, normal or elevated IgM, and defective class switch recombination and somatic hyper-mutation, are heterogeneous disorders with at least six distinct molecular defects, including the CD40 ligand (CD40L) and IKK-gamma (NEMO) genes (both X-linked), the CD40, Activation-Induced Cytidine DeAminase (AICDA), and Uracil-DNA Glycosylase (UNG) genes (autosomal recessive), and IKBA (autosomal dominant). Our objective was to determine the molecular basis and clinical features of Taiwanese patients with the HIGM phenotype METHODS:: Clinical manifestations and candidate genes were analyzed in a nationwide population-base study. RESULTS:: Among 14 patients (12 unrelated families) since 2003, 10 patents were identified (8 families) with CD40L mutations, including two novel deletions of "A" nucelotide, both frameshift and stop at the 127 location; one novel AID deletion mutation lack of the 37Asp and 38Ser; one ataxia-teleangiectasia mutation (ATM); and one deletion of chromosome 1q42. An adult-onset patient with mutant [Thr254Met]CD40L had approximately 30% detectable affinity and therefore less severity. Memory-B cells decreased in patients with CD40L and AICDA mutations. Three mortalities encompassed renal cell carcinoma in one patient with [Tyr169Asn]CD40L, pneumothorax in one with [Tyr140Stop]CD40L, and pneumonia after chemotherapy in an A-T patient. One patient without detectable genetic defects but normal lymphocyte proliferation resembled the mild form of CVID phenotype. CONCLUSIONS:: In contrast to those with AID mutation, small chromosome 1 q42 deletion and unknown genetic defect, the majority (10/14; 71.4%) with CD40L mutations except [Thr254Met] and an A-T patient had the severe form of HIGM phenotype.
The Pediatric Infectious Disease Journal 03/2013; · 3.58 Impact Factor
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ABSTRACT: Background: Asthma is characterized as a chronic inflammatory disorder of the airways associated with an enhanced TH2 response to inhaled allergens. CD4+ T regulatory (Treg) cells are controlled by the master transcription factor FoxP3 and strictly maintain peripheral immunotolerance. Epigenetic regulation of FoxP3 by DNA methyltransferase inhibitors, such as 5-azacytidine (Aza), can generate a steady supply of functional Treg cells. Therefore, we propose that Aza can augment Treg cells in vivo to prevent the pathogenesis of asthma. Methods: BALB/c mice were sensitized with chicken ovalbumin (OVA) and treated with different doses of Aza. Airway hyperresponsiveness to methacholine, eosinophilia in bronchoalveolar lavage fluid, circulating titers of OVA-specific IgG1 and IgE, and stimulating levels of TH2 cytokines from splenocytes were then determined. Cellular populations were examined by flow cytometry. PC61 antibody, which depletes CD25+ cells, was used to verify the role of CD25+ cells in Aza-induced tolerance. Results: Administration of Aza to OVA-sensitized mice diminished airway hyperreactivity, pulmonary eosinophilia, levels of OVA-specific IgG1 and IgE in serum, and secretion of TH2 cytokines from OVA-stimulated splenocytes in a dose-dependent manner. Percentages of CD25+ and FoxP3+ cells in the CD4+ cell population were notably increased in Aza-treated mice compared to sensitized control mice. Furthermore, the major symptoms of asthma were exacerbated by depleting CD25+ cells in Aza-treated mice. Conclusions: Aza may have applications as a novel clinical strategy to increase the production of Treg cells in order to modulate the airway inflammation associated with asthma.
International Archives of Allergy and Immunology 11/2012; 160(4):356-364. · 2.40 Impact Factor
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Wen-I Lee,
Shih-Hsiang Chen,
Jing-Long Huang,
Tang-Her Jaing,
Hung-Tao Chung,
Kuo-Wei Yeh, Li-Chen Chen,
Tsung-Chieh Yao,
Meng-Ying Hsieh,
Syh-Jae Lin,
Ming-Ling Kuo
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ABSTRACT: To differentiate severe congenital neutropenia (SCN) from autoimmune neutropenia (AIN) in patients with persistent neutropenia ≤1000/mm(3) over three months, we evaluated anti-neutrophil auto-antibodies, candidate genes of ELANA, HAX1 and GCSFR, and neutrophil elastase (NE) activity in 38 patients (21 females; average onset age 14.12±2.49 months) in a primary immunodeficiency disease center between 2004 and 2011. In 30 patients, detectable anti-neutrophil auto-antibodies were HNA1a in 16 patients, HNA1c in 15, MHC Class I in 14, HNA1b in eight, MHC Class II in five, and HNA2a in three. Their average neutropenia duration was 27.04±2.08 months. Of eight patients without detectable auto-antibodies, three had ELANE mutations [Ser126Pro, Arg170Phe and Cys223stop] and recurrent muco-cutaneous infections and sepsis. The patient with nonsense ELANE mutation [Cys223stop] had the lowest NE activity (16.8). Thus, patients with ELANE mutations have undetectable antibodies and more severe and younger-onset muco-cutaneous infections, prolonged healing and decreased serum NE activity that require prompt intervention.
Immunobiology 10/2012; · 3.20 Impact Factor
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ABSTRACT: Asthma is a chronic airway inflammatory disease characterized by eosinophilic infiltration and airway hyperresponsiveness. The over-activated Th2 and lung epithelium cells express many different cytokines and chemokines mainly contribute to the severity of lung inflammation. Clara cell 10 kD protein (CC10) that is highly expressed in airway epithelium cells and exhibits anti-inflammatory and immunomodulatory effects. Adeno-associated virus (AAV) 2/9 vector, composed with AAV2 rep and AAV9 cap genes, can efficiently and specifically target lung epithelium cells. Thus, AAV2/9 vector might carry therapeutic potential gene sequences for the treatment of asthma. This study tested whether AAV2/9 vector carrying CC10 could reduce inflammatory and asthmatic responses in OVA-induced asthmatic mouse model. The results showed that AAV2/9-CC10 vector virus significantly reduced airway hyperresponsiveness, CCL11, IL-4, IL-5, IL-6, IL-13, and eosinophilia in the lungs of sensitized mice. CC10 level in OVA-sensitized mice was rescued with the administration of AAV2/9-CC10 vector virus. Lung tissue remodeling, including collagen deposition and goblet cell hyperplasia was also alleviated. However, serum levels of OVA-specific IgG1 and IgE as well as Th2 cytokine levels in OVA-stimulated splenocyte culture supernatants were at the comparable levels to the sensitized control group. The results demonstrate that AAV2/9-CC10 vector virus relieved local inflammatory and asthmatic responses in lung. Therefore, we propose that AAV2/9-CC10 vector virus guaranteed sufficient CC10 expression and anti-inflammatory effect in asthmatic mice. It might be applied as a novel therapeutic approach for asthma.
Human gene therapy 09/2012; · 4.20 Impact Factor
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ABSTRACT: Abstract Airway infiltration by eosinophils is a major characteristic of chronic asthma. CCL11 (eotaxin-1) is secreted by lung epithelial cells and functions as the major chemokine for eosinophil recruitment. Pseudotyped adeno-associated virus (AAV) 2/9, composed by the AAV2 rep and AAV9 cap genes, can efficiently target lung epithelial cells and might carry gene sequences with therapeutic potential for asthma. This study aimed to determine whether pseudotyped AAV2/9 virus carrying the small hairpin RNA targeting CCL11 and expressed by CMV/U6 promoter could reduce eosinophilia and asthmatic responses in mite allergen-sensitized mice. Mice were sensitized by intraperitoneal and challenged by intratracheal injection with recombinant Dermatophagoides pteronyssinus group 2 allergen (rDp2). AAV2/9 viral vectors were intratracheally injected three days before the first challenge. AAV2/9 sh47 virus significantly reduced airway hyperresponsiveness, airway resistance, CCL11 levels, and eosinophilia in the lungs of sensitized mice. Th2 cytokines, including interleukins (IL)-4, IL-5, and IL-10, were also significantly reduced in the bronchoalveolar lavage fluid of AAV2/9 sh47 virus-treated mice. Th2 cytokine levels were also reduced in rDp2-stimulated mediastinal lymphocytes in treated mice. However, serum levels of rDp2-specific IgG1 and IgE, as well as Th2 cytokine levels in rDp2-stimulated splenocyte culture supernatants, were comparable to the sensitized control group. The results suggest that AAV2/9 sh47 virus relieved local instead of systemic inflammatory responses. Therefore, the CMV/U6 promoter with AAV2/9 viral vector, which is preferable to target lung epithelia cells, might be applied as a novel therapeutic approach for asthma.
Human gene therapy 08/2012; · 4.20 Impact Factor
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Li-Chen Chen,
Hsu-Min Tseng,
Chia-Jen Wu,
Ming-Ling Kuo,
Cheng-Jang Wu,
Pei-Song Gao,
Kuo-Wei Yeh,
Tsung-Chieh Yao,
Wen-I Lee,
Liang-Shiou Ou,
Jing-Long Huang,
Shau-Ku Huang
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ABSTRACT: The gene (SCGB1A1) encoding Clara cell 10-kDa protein (CC10), a steroid-inducible immune modulator, is a candidate gene for asthma, but the evidence is equivocal. The potential influence of a common variant on asthma severity and serum CC10 levels during acute exacerbation and after corticosteroid treatment in Chinese case-control children and its functional relevance was investigated.
Genotyping of a non-coding variant G+38A was performed in 489 children, of whom 277 had asthma with varying severity, and 212 healthy controls. Associations were tested for asthma, asthma severity, and responsiveness to steroid treatment. The transcriptional activity of this variant was examined in a Clara-like cell line (H358) using transient transfection assays.
Significant association was observed for the combined GA and AA genotypes of the CC10 G+38A variant and an increased risk of asthma [odds ratio (OR), 2.62, p < .001]. This association was correlated with asthma severity (moderate: OR, 2.85, p < .001; near-fatal: OR, 4.81, p < .001). Also, patients with the GA and AA genotypes showed significantly lower serum CC10 (p < .01) and provocation concentration causing a 20% fall (PC(20)) in forced expiratory volume in 1 s (FEV(1)) (p < .0001) when compared with those with the GG. After glucocorticoid treatment, the CC10 levels were significantly increased in asthmatic patients with GG (p < .0001), but not those with the GA and AA genotypes. Moreover, a lower dexamethasone-induced reporter (luciferase) activity was observed for H358 cells transiently transfected with the G38A risk allele (A) compared with wild-type allele (G).
These findings suggest that the CC10 G+38A variant may contribute to the severity of asthma and lower level of steroid responsiveness.
Journal of Asthma 07/2012; 49(7):665-72. · 1.52 Impact Factor
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ABSTRACT: BACKGROUND/PURPOSE: The aim of the study was to describe the clinical features of children affected by juvenile idiopathic arthritis (JIA) under the International League of Associations for Rheumatology-derived classification criteria in a community-based setting. METHODS: Consecutive cases of JIA from defined geographic areas of Taiwan were diagnosed and followed in an observational cohort from 1995 to 2010. In addition to the clinical and laboratory data required for the International League of Associations for Rheumatology system, information about the medication and disease activity during the study period was also recorded. RESULTS: Out of 292 children with chronic joint pain, 195 were diagnosed as JIA: systemic arthritis (19%), oligoarthritis (persistent 16.4%; extended 6.7%), polyarthritis rheumatoid factor-negative (11.8%), polyarthritis rheumatoid factor-positive (4.6%), psoriatic arthritis (1.5%), enthesitis-related arthritis (ERA; 37.4%), and undifferentiated arthritis (2.6%). Human leukocyte antigen-B27 was positive in 82.2% of patients with ERA. Uveitis was observed in 6.7% of patients. Disease-modifying anti-rheumatic drugs, including biologic medications, were used in 73.3% of children during the observational period. At the last follow-up, 40% of patients experienced a continuously active or relapsing course. CONCLUSION: Compared with previous reports on Western populations, a remarkably high prevalence was found in the ERA of the Chinese cohort, but a relatively low rate of uveitis. Ongoing disease activity was evident in a substantial number of children. These results provided a good starting point in understanding the epidemiology of this serious disease in the Chinese population.
Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi 06/2012; · 0.99 Impact Factor
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ABSTRACT: Toll-like receptors (TLR) initiate innate and often affect adaptive immune response. This study aimed to determine if TLR response and T regulatory cell (Treg) function in peripheral blood mononuclear cells (PBMC) correlate with clinical severity in non-infectious asthma. TLR1-9 expression and representative response cytokine TNF-α, IL-6, and IFN-β secretions were analyzed after stimulation by TLR1-9 ligands from 17 non-infectious asthmatic children. TNF-α production was higher in TLR1/2 (median 385.4 vs. 250.3pg/ml in 1μg/ml Pam3CSK4, p=0.0078), TLR4 (2392.4 vs. 1355.9 in 1μg/ml LPS; p=0.0005), and TLR7/8 (10,776.2 vs. 4237.0pg/ml in 1μg/ml R848, p=0.0079) of patients in exacerbation than those in convalescence and healthy controls despite equal TLR expression. TNF-α production stimulated by TLR9 agonist was significantly lower in exacerbation (17.7 vs. 34.9pg/ml in 1μg/ml ODN2216, p=0.0175), while IL-6 production had similar patterns but was significantly lower in TLR3 signaling (119.7 vs. 245.0pg/ml in 0.1μg/ml poly(I:C), p=0.0033). IFN-β production by TLR3 agonist also decreased in exacerbation but not statistically significant. Six older children showed decreased FOXP3 percentage in CD4+CD25(high) and decreased suppression capability in exacerbation but restored in stabilization (82.8% vs. 90.0%, p=0.0061 and 60.9% vs. 81.7%, p=0.0071; respectively). In conclusion, normalizing imbalanced TLR signaling and enhancing Treg cell capability may guide possible therapeutic strategies for non-infectious asthma in exacerbation.
Immunobiology 05/2012; · 3.20 Impact Factor
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Wen-I Lee,
Jing-Long Huang,
Tang-Her Jaing,
Shyh-Dar Shyur,
Kunder D Yang,
Yin-Hsiu Chien,
Bor-Luen Chiang,
Wen-Jue Soong,
Shyh-Shin Chiou,
Chi-Chang Shieh, [......],
Hong-Ren Yu,
Hsiu-Ju Yen,
Meng-Ying Hsieh,
Ming-Ling Kuo,
Wuh-Liang Hwu,
Yi-Chan Tsai,
Ho-Chang Kuo,
Yi-Ling Lin,
Ying-Fan Shih,
Kuei-Wen Chang
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ABSTRACT: Primary immunodeficiency diseases (PIDs) are a group of rare diseases with wide geographic and ethnic variations in incidence, prevalence, and distribution patterns. The aim of this study was to examine the distribution pattern and clinical spectrum of PIDs in Taiwan at a national referral institute. From 1985 to 2010, 215 patients from 183 families were diagnosed and grouped according to the updated classification of PIDs. Eighty-one (37.7%) patients had "other well-defined immunodeficiency syndromes", followed by "predominantly antibody deficiencies" (54 patients; 25.1%), "T- and B-cell immunodeficiencies" (34; 15.8%), "congenital defects of phagocytes" (25; 20.2%), "complement deficiencies" (15; 7.0%), and "disease in immune dysregulation" (5; 2.3%). The last category included two patients with Chediak-Higashi syndrome, and one each with familial hemophagocytosis, IPEX, and hypogammaglobulinemia and albinism. One female had cold-induced auto-inflammatory disease. There were no cases of "defects in innate immunity". Pseudomonas and Streptococcus pneumoniae were the two most identified microorganisms in septicemia (42.7%; 44/103 episodes). Stem cell transplantation was successful in 13 of 22 patients, while 34 patients (15.8%) died. Molecular defects were identified in 109 individuals (from 90 families). There were relatively fewer cases of "predominantly antibody deficiencies" due to there being only a few patients with adult-onset PIDs, implying certainty bias rather than ethnic variation. Awareness of under-diagnosis among physicians rather than pediatricians is vital for timely diagnosis and consequently adequate treatment.
Immunobiology 06/2011; 216(12):1286-94. · 3.20 Impact Factor
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ABSTRACT: Little is known about the prevalence of allergic diseases in children of different ages. This study aimed to investigate the prevalence of allergic diseases and allergic sensitization in children over a wide age range, with emphasis on the influence of age, gender, and body mass index (BMI).
In a cross-sectional study, we assessed 5351 Taiwanese children aged 4-18 years using an International Study of Asthma and Allergies in Childhood questionnaire, BMI, and total and specific serum immunoglobulin E.
Forty-eight percent were currently symptomatic for at least one of three allergic diseases. Prevalence of wheeze ever, current wheeze, and diagnosed asthma were 17.0%, 7.5%, and 9.8%, respectively; analogous features for rhinitis were 47.8%, 44.2%, and 39.8%. Allergic sensitization was very common (57.3%). Half of the children (50.6%) with current wheeze had not been diagnosed with asthma by physicians, whereas undiagnosed rates were 32.3% for rhinitis and 25.3% for eczema. The male-to-female prevalence ratios of current wheeze increased with age from <1 at 4-5 years, peaked at 10-11 years (2.24), then reversed to 0.57 at 16-18 years. Childhood wheezing tended to remit with age, but rhinitis and eczema were more persistent. Total immunoglobulin E levels increased with age until 14-15 years, and declined thereafter. Elevated BMI was associated with greater prevalence of wheezing and eczema, with no evidence of significant effect modification by either gender or age. Multivariate analyses revealed that younger age, boys, and obesity were significantly and independently associated with current wheezing in children (all p < .01).
The burden and co-morbidity of childhood allergies are substantial. There are striking age-dependent gender differences in asthma prevalence, exhibiting an inverted U-shaped curve for male-to-female prevalence ratios by age. Obesity is associated with a greater prevalence of asthma in children with no evidence of a significant modulation by either gender or age.
Journal of Asthma 06/2011; 48(5):503-10. · 1.52 Impact Factor
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ABSTRACT: Traditional asthma prevalence surveys were based on the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire, which focuses on children aged 6-7 and 13-14. However, asthma-like symptoms usually commence in preschool aged children, in whom it is difficult to make a definite diagnosis of asthma. It is worth determining the prevalence rate of asthma or asthma-like symptoms and analyzing the risk factors for this phenomenon among preschool aged children.
Children aged 3-6 years were recruited from kindergartens in Keelung City, northern Taiwan. The questionnaire used was based on the ISAAC phase III core and environmental questionnaires and included questions on asthma, rhino-conjunctivitis, and eczema, along with questions to elicit common and early presentations of asthma, as well as other demographic and environmental data. The questionnaires were delivered and completed by parents.
2395 questionnaires were delivered to parents with children at 50 kindergartens, of which 2170 questionnaires were returned (return rate 90.6%). 9.9% of these preschool children had physician-diagnosed asthma. However, 20.4% of them experienced asthma like symptoms while attending kindergarten. Both the physician-diagnosed asthma and asthma-like symptoms groups had more clinical symptoms in all seasons except summer, compared to children without asthma. It was significant that the asthma-like symptoms commenced after joining a kindergarten (p < 0.001), and 66.5% of the children started to experience the symptoms within one month of beginning kindergarten. Using antibiotics or antipyretics in young infancy and mothers having asthma were the risk factors for developing asthma and asthma-like symptoms (p < 0.001), but parental smoking was not contributory to asthma development in preschool children. More frequent use of antipyretics in a year had a higher risk for the development of asthma and asthma-like symptoms.
Asthma and asthma-like symptoms were common in preschool children. Early infection of the respiratory tract and use of antibiotics were associated with presentation of symptoms. Attending a kindergarten is also a risk factor for early presentation of asthma among preschool children.
Asian Pacific journal of allergy and immunology / launched by the Allergy and Immunology Society of Thailand 06/2011; 29(2):120-6. · 0.65 Impact Factor
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Wen-I Lee,
Jing-Long Huang,
Syh-Jae Lin,
Kuo-Wei Yeh, Li-Chen Chen,
Liang-Shiou Ou,
Tsung-Chieh Yao,
Meng-Ying Hsieh,
Yhu-Chering Huang,
Hong-Ren Yu,
Ho-Chang Kuo,
Kunder D Yang,
Tang-Her Jaing
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ABSTRACT: Hyper-immunoglobulin E recurrent infection syndromes (HIES) have distinct features, with identified associated mutations of STAT3, TYK2, and DOCK8. Among 197 Taiwanese patients with primary immunodeficiency on a referral-base of over 23 million inhabitants, STAT3 (R382W and Q469R) and DOCK8 mutations (exon 1-9 deletion) were identified in two patients each from six AD-HIES and five AR-HIES patients, respectively. Aside from decreased Th17 and memory B cells, characteristic facies and pneumatocele were not mutually exclusive regardless of STAT3 and DOCK8 mutations. One with novel DOCK8 deletion had notable cytomegalovirus retinitis, cerebral vasculitis, lead deposition, and amenorrhea. In adolescence, three AD-HIES patients without STAT3 mutation died of myocardial infarction, staphylococcus sepsis, and proteus sepsis while receiving chemotherapy for lymphoma. Close follow-up of the HIES phenotype rather than identifying genetic mutations should be the cornerstone of intervention at this juncture because of relatively lower percentage of identifying mutations in Taiwanese HIES (4/11; 36.5%).
Immunobiology 01/2011; 216(8):909-17. · 3.20 Impact Factor
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Wen-I Lee,
Jing-Long Huang,
Shy-Jae Lin,
Kuo-Wei Yeh, Li-Chen Chen,
Meng-Ying Hsieh,
Yhu-Chering Huang,
Ho-Chang Kuo,
Kunder D Yang,
Hong-Ren Yu,
Tang-Her Jaing,
Chih-Hsun Yang
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ABSTRACT: Hyper-immunoglobulin E recurrent infection syndromes (HIES) has characteristic features and identified mutations. This study investigated clinical features and causal candidate mutations in Taiwanese patients with the HIES phenotype on referral base over 23 million inhabitants.
Clinical manifestations of the HIES phenotype, severity scoring, immunological functions and candidate genes of signal transducer and activator of transcription 3 (STAT3), tyrosine kinase 2 (TYKZ), and dedicator of cytokineses 8 (DOCK8) were analyzed.
Between 1985 and 2009, six sporadic and two siblings met HIES criteria (onset age: 2-54 months; severity score: 31-65) out of 187 patients with primary immunodeficiencies. Five patients with the autosomal dominant (AD)-HIES phenotype presented as pneumatocoele, bronchiectasis, retained primary teeth, minor trauma fracture, scoliosis, coronary aneurysm, and lymphoma. Three with the autosomal recessive (AR)-HIES phenotype and impaired lymphocyte proliferation function had herpes simplex virus infection, molluscum contagiosum, and cerebral vasculitis. Notably in one patient with the AR-HIES phenotype, unintentional lead component in traditional application herbs for accelerating wound healing deposited in basal ganglia and aggravated involuntary movement relative to cerebral vacculitis. Those with mildly elevated memory T cells and decreased memory B cells trended to develop arteritis. Of five AD-HIES patients, three were mortalities from acute myocardial infarction, Proteus mirabilis, and Staphylococcus aureus sepsis. Only one had de novo novel STAT3 (Gln 469 Arg) mutation with "relative" lower HIES STAT3 score.
Known genetic defects responsible for the HIES phenotype are not so common in Taiwan. This may infer genetic variations in different ethnicities although selection bias and under-diagnosis for HIES with known genetic defects could be contribution factors.
Journal of Clinical Immunology 12/2010; 31(2):272-80. · 3.08 Impact Factor
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ABSTRACT: Abdominal pain in systemic lupus erythematosus (SLE) patients has rarely been analyzed in pediatric populations. We planned to investigate the potential differences between childhood-onset and adult-onset SLE patients who were hospitalized because of acute abdominal pain.
A retrospective study including 23 childhood-onset SLE patients with 38 admissions and 88 adult-onset SLE patients with 108 admissions from 1999 to 2008 were conducted in our hospital. All of them had the chief complaint of diffuse abdominal pain.
The etiologies of acute abdominal pain in adult-onset SLE patients were more diverse than childhood-onset SLE patients. The most common cause of acute abdominal pain in SLE patients was lupus mesenteric vasculitis (LMV) (18.5%), followed by acute gastroenteritis (14.4%), pancreatitis (10.3%), appendicitis (7.5%), and cholecystitis (6.2%). Compared with adults, children were admitted more often due to LMV (31.6% versus 13.9%; P = 0.016), had more frequently recurrent episodes (39.1% versus 14.8%; P = 0.009), and were more often treated with immunosuppressive agents (31.6% versus 7.4%; P < 0.001) at the time of admission. The overall case fatality rate of acute abdomen in SLE patients was 9.4%. The extra-gastrointestinal symptoms, laboratory evaluation, disease activity, and organ damage measured by the SLE Disease Activity Index and outcomes were comparable between children and adults.
Various etiologies of acute abdominal pain should be considered in SLE patients. LMV is the most common cause of acute abdomen in childhood-onset SLE patients with low mortality and morbidity provided by prompt diagnosis and timely administration of high-dose intravenous corticosteroids after excluding real surgical abdomen.
Seminars in arthritis and rheumatism 09/2010; 40(5):447-54. · 4.72 Impact Factor
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ABSTRACT: To characterize the atherosclerotic risk factors in the progression of subclinical atherosclerosis in patients with juvenile-onset systemic lupus erythematosus (SLE).
This was a longitudinal study of 76 patients with juvenile-onset SLE. Carotid arteries were evaluated using ultrasonography at baseline and at followup visits at 6-month intervals over the 6-year study period. Clinical and laboratory parameters, disease activity, treatment, and traditional risk factors for atherosclerosis were evaluated. Data were analyzed using generalized estimating equations.
The mean+/-SD age of the patients at baseline was 15.01+/-3.48 years and the mean+/-SD disease duration was 2.65+/-2.5 years. The mean+/-SD duration of followup was 3.74+/-1.24 years. The mean+/-SD intima-media thickness (IMT) of the common carotid arteries differed significantly between the patient and control (n=38) groups (0.63+/-0.08 mm versus 0.54+/-0.06 mm; P<0.001). The presence of lymphopenia at diagnosis and at baseline and higher levels of serum creatinine and C-reactive protein at baseline were positively associated with progression of carotid IMT (P=0.006, P=0.043, P=0.037, and P=0.049, respectively). In multivariate analysis, only lymphopenia at baseline and at diagnosis were consistently associated with progression of IMT (P=0.012 and P=0.045, respectively).
In patients with juvenile-onset SLE, some nontraditional risk factors for the progression of subclinical atherosclerosis were identified. Lymphopenia was the only independent risk factor for the progression of IMT. The pathogenic mechanisms warrant further investigation.
Arthritis & Rheumatism 11/2009; 60(12):3766-75. · 7.87 Impact Factor
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Journal of pediatric gastroenterology and nutrition 07/2009; 49(2):251-3. · 2.18 Impact Factor
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ABSTRACT: Monocyte chemotactic protein 1 (MCP-1) plays an important role in various immune and allergic disorders since it is a potent chemo-attractant for inflammatory cells, such as eosinophils, memory T cells, and monocytes.
To investigate serum MCP-1 during asymptomatic state and acute attacks of bronchial asthma.
In this longitudinal cohort design study, sequential serum levels of MCP-1 were measured by a sandwich enzyme-linked immunosorbent assay (ELISA). Twenty-four asthma patients' MCP-1 levels were examined at 5 time points: during the asymptomatic phase, in an acute wheezing episode, and at 1 week, 1 month, and 2 months after acute asthma attack. Fifteen children without asthma were enrolled as control.
During the asymptomatic phase of asthma, serum MCP-1 levels were significantly higher than that of normal controls (329.57 +/- 99.20 pg/ml vs. 213.63 +/- 77.29 pg/ml, p = 0.001). In comparison with the asymptomatic phase, the serum MCP-1 levels during the acute asthma attack were significantly higher (682.88 +/- 88.45 pg/ml vs. 329.57 +/- 99.20 pg/ml, p < 0.001). After treatment of acute asthma exacerbation, all of the serum MCP-1 levels declined within 1 week, but were still higher than control 2 months later.
In asthma patients, the consistently elevated serum levels of MCP-1 suggest its role in the pathogenesis of bronchial asthma - not only in the chronic inflammatory processes, but also in acute asthma attack exacerbation. These findings suggest a possible role for MCP-1 in the pathogenesis of asthma and a potential role for its use in anti-asthma treatment in the future.
Journal of Asthma 04/2009; 46(3):225-8. · 1.52 Impact Factor
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ABSTRACT: Systemic lupus erythematosus (SLE) patients had an increased susceptibility to tuberculosis (TB). The aim of this study was to investigate the prevalence and clinical characteristics of TB in SLE patients, with focus on the differences between pulmonary and extra-pulmonary TB. This is a retrospective study that reviewed the medical records of 3,179 SLE patients from 1985 to 2004. The diagnosis of TB was confirmed by one of the following: positive acid-fast bacillus (AFB) smear, positive culture of Mycobacterium tuberculosis from appropriate specimens, or a histopathologic finding of caseating granuloma on specimen. During the 20-year review period, TB was documented in 19 SLE patients, with 21 episodes. Ten of 21 episodes (47.6%) were pulmonary TB while the other 11 episodes (52.4%) were extra-pulmonary TB. Among extra-pulmonary TB, there were joint and cutaneous involvements in five, miliary in two, Pott's disease in two, peritoneum in one, and spleen in one. The most common manifestations of TB were fever and cough. Delayed diagnosis and adverse effects of anti-TB therapy were observed in the extra-pulmonary TB group. While SLE patients commonly present with prolonged fever or chronic cough, tuberculosis infection should be taken into consideration.
Clinical Rheumatology 06/2008; 27(5):557-63. · 2.00 Impact Factor
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ABSTRACT: Seven known genetic defects, including Bruton tyrosine kinase (Btk), CD4OL, and signaling lymphocyte activation molecule-associated protein (SAP) (all X-linked) and inducible costimulator molecule (ICOS), transmembrane activator and calcium-modulator and cytophilin ligand interactor (TACI), B-cell-activating factor of the tumor necrosis family receptor (BAFFR), and CD19 (all autosomal recessive), were found in patients with the phenotype of common variable immunodeficiency (CVID).
To investigate these 7 candidate protein expressions and candidate gene sequences for comprehensive analysis of known genetic defects in patients with CVID.
These 7 candidate protein expressions were evaluated by flow cytometry or Western blot, and candidate genes were evaluated by direct sequencing.
Of 9 CVID patients from a single Taiwanese tertiary care hospital, we identified 2 cousins with decreased Btk expression who had a mutated (Asp521Val) kinase domain of Btk (1694A>T in exon 15) and 1 patient with decreased CD40L expression who had a mutated (Thr254Met) extracellular domain of CD40L (782T>C in exon 5).
This comprehensive approach revealed that, in Taiwan, in some patients mild forms of X-linked agammaglobulinemia and hyper-IgM syndrome caused the CVID phenotype. No mutations of SAP, ICOS, TACI, BAFFR, and CD19 were identified in this study, although selection bias among the small study population and genetic variation may exist.
Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology 12/2007; 99(5):433-42. · 2.83 Impact Factor
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ABSTRACT: Wheezing episodes are common in young infants. However, the molecular mechanism of wheezing is unclear, and very few therapeutic regimens are effective.
This study investigated the genetic and environmental factors predisposing to infant wheezing in a birth cohort study.
A cohort of 1211 pregnant women was recruited for this study. Infant wheezing episodes during the first 18 months of life were correlated to parental atopic history, parental smoking, prematurity, CB IgE levels, and the sequence variant (G+38A) of the Clara cell protein 10 (CC10) gene encoding a secretary anti-inflammatory CC10 protein.
Nine hundred eighty-three infants completed umbilical cord blood collection, and 813 infants completed the 18-month postnatal follow-up. Twenty-two percent of the infants experienced at least 1 wheezing episode, and 6.6% of the infants experienced frequent wheezing (> or =3 episodes). Multivariate logistic regression showed that male sex and the CC10 G+38A polymorphism, but not prematurity, CB IgE level, passive smoking, or parental atopy, were predictors of frequent wheezing. Further studies found that infant frequent wheezing was significantly associated with the CC10 +38AA genotype and lower plasma CC10 levels at 18 months of age (P = .046), and infants with acute wheezing episodes had significantly lower CC10 levels than those without (P = .023). No association of wheezing episodes with allergic sensitization was observed in this cohort population.
Infant frequent wheezing is associated with the CC10 G+38A polymorphism and lower CC10 levels but not infant atopy.
Lower CC10 expression, but not allergy sensitization, is involved in the pathogenesis of infant frequent wheezing.
Journal of Allergy and Clinical Immunology 10/2007; 120(4):842-8. · 11.00 Impact Factor
