Clinical and Immunological Defects and Outcomes in Patients with Chromosome 22q11.2 Deletion Syndrome.

BACKGROUND: Chromosome 22q11.2 deletion syndrome (22q11.2DS) is the most common microdeletion syndrome in humans and can present with highly variable clinical manifestations. Immune deficiencies occur because of thymic hypoplasia or aplasia. METHODS: This retrospective study included patients diagnosed with 22q11.2DS at a medical center between 2000 and 2021. We analyzed the association between clinical phenotypes, immunological abnormalities, age, and outcomes. RESULTS: Eighty-seven patients with 22q11.2DS had a median diagnostic age of 1.78 months. Patients presented with congenital heart disease (CHD; 86.2%), major infections (75.9%), and failure to thrive (FTT; 58.6%). Autoimmunity, neuropsychiatric disorders, and hypoparathyroidism were significantly associated. Neonatal seizures were associated with early diagnosis before 2 months (OR 8.56, 95% CI 1.21-60.58, P = 0.032). Immunological abnormalities included lymphopenia (93.1%), T lymphopenia (71.9%), CD4+ T lymphopenia (64.1%), a lack of hepatitis B vaccine antibodies (46.2%), and complete DiGeorge syndrome (cDGS) (2.3%). Severe lymphopenia and T lymphopenia improved at 3 years of age. Two patients with cDGS were treated with hematopoietic stem cell transplantation, and one survived. The mortality rate was 12.8% and the estimated 35-year survival probability was 77.5%. Major infections experienced > four times were significantly associated with a decreased survival rate of 60%. Patients with CHD without FTT or recurrent infections had a better 20-year survival rate (96.2%). CONCLUSIONS: CHD, major infection, and FTT were common manifestations and poor prognostic factors. Autoimmunity, neuropsychiatric disorders, and hypoparathyroidism were significantly associated. Although T lymphopenia may improve with age, patients with 22q11.2DS require lifelong monitoring for immune dysregulation.

Predictive characteristics to discriminate the longitudinal outcomes of childhood asthma: a retrospective program-based study.

BACKGROUND: Childhood asthma is an inflammatory disease with heterogeneous outcomes. We sought to determine the impact of total IgE, blood eosinophil, allergen sensitization, and inhaled corticosteroid (ICS) on longitudinal outcomes and to identify characteristics for discriminating different outcomes. METHODS: We conducted a retrospective study in 383 childhood asthma patients and another 313 patients with blood eosinophil data only receiving regular program-based visits from September 1, 2004, to December 31, 2018. Peak expiratory flow (PEF) variability, PEF predicted %, asthma severity, and asthma control at each visit were assessed as clinical outcomes. RESULTS: Our data show that the percentage of blood eosinophils was significantly associated with increased asthma severity (OR: 1.043, 95% CI: 1.002-1.086, P = 0.0392). Mold sensitization was significantly associated with asthma severity (OR: 2.2485, 95% CI: 1.3253-3.8150, P = 0.0027). Characteristics including sensitization status plus ICS dosage had the best area under the receiver operating characteristic curve (AUC) value for predicting longitudinal PEF predicted % (0.6609), PEF variability (0.6885), asthma severity (0.5918), and asthma control (0.6441), respectively. CONCLUSIONS: We showed that the risk for adverse clinical outcomes at follow-up differed between serum IgE, blood eosinophil, and allergen sensitization identified at baseline. Sensitization and ICS dosage were predictive characteristics of long-term clinical outcomes. IMPACT: The unique aspects of the study are its longitudinal assessment of patients receiving guideline-based asthma management program to help characterize the stability of the clinical outcomes over time. Characteristics including allergen sensitization and ICS dosage demonstrated an improved capability for distinguishing between better and worse clinical outcomes. Through longitudinal serial assessment, this study indicates the risk for adverse clinical outcomes differed between children with serum IgE/blood eosinophil/allergen sensitization characterized at baseline.

Efficacy and safety of anti-CD45-saporin as conditioning agent for RAG deficiency.

BACKGROUND: Mutations in the recombinase-activating genes cause severe immunodeficiency, with a spectrum of phenotypes ranging from severe combined immunodeficiency to immune dysregulation. Hematopoietic stem cell transplantation is the only curative option, but a high risk of graft failure and poor immune reconstitution have been observed in the absence of myeloablation. OBJECTIVES: Our aim was to improve multilineage engraftment; we tested nongenotoxic conditioning with anti-CD45 mAbs conjugated with saporin CD45 (CD45-SAP). METHODS: Rag1-KO and Rag1-F971L mice, which represent models of severe combined immune deficiency and combined immune deficiency with immune dysregulation, respectively, were conditioned with CD45-SAP, CD45-SAP plus 2 Gy of total body irradiation (TBI), 2 Gy of TBI, 8 Gy of TBI, or no conditioning and treated by using transplantation with lineage-negative bone marrow cells from wild-type mice. Flow cytometry and immunohistochemistry were used to assess engraftment and immune reconstitution. Antibody responses to 2,4,6-trinitrophenyl-conjugated keyhole limpet hemocyanin were measured by ELISA, and presence of autoantibody was detected by microarray. RESULTS: Conditioning with CD45-SAP enabled high levels of multilineage engraftment in both Rag1 mutant models, allowed overcoming of B- and T-cell differentiation blocks and thymic epithelial cell defects, and induced robust cellular and humoral immunity in the periphery. CONCLUSIONS: Conditioning with CD45-SAP allows multilineage engraftment and robust immune reconstitution in mice with either null or hypomorphic Rag mutations while preserving thymic epithelial cell homeostasis.

Hematopoietic stem cell transplantation for progressive combined immunodeficiency and lymphoproliferation in patients with activated phosphatidylinositol-3-OH kinase δ syndrome type 1.

BACKGROUND: Activated phosphatidylinositol-3-OH kinase δ syndrome type 1 (APDS1) is a recently described primary immunodeficiency syndrome characterized by recurrent respiratory tract infections, lymphoid hyperplasia, and Herpesviridae infections caused by germline gain-of-function mutations of PIK3CD. Hematopoietic stem cell transplantation (HSCT) can be considered to ameliorate progressive immunodeficiency and associated malignancy, but appropriate indications, methods, and outcomes of HSCT for APDS1 remain undefined. OBJECTIVE: Our objective was to analyze the clinical manifestations, laboratory findings, prognosis, and treatment of APDS1 and explore appropriate indications and methods of HSCT. METHODS: We reviewed retrospectively the medical records of cohorts undergoing HSCT at collaborating facilities. RESULTS: Thirty-year overall survival was 86.1%, but event-free survival was 39.6%. Life-threatening events, such as severe infections or lymphoproliferation, were frequent in childhood and adolescence and were common indications for HSCT. Nine patients underwent HSCT with fludarabine-based reduced-intensity conditioning. Seven patients survived after frequent adverse complications and engraftment failure. Most symptoms improved after HSCT. CONCLUSION: Patients with APDS1 showed variable clinical manifestations. Life-threatening progressive combined immunodeficiency and massive lymphoproliferation were common indications for HSCT. Fludarabine-based reduced-intensity conditioning-HSCT ameliorated clinical symptoms, but transplantation-related complications were frequent, including graft failure.

Clinical manifestations and anti-TNF alpha therapy of juvenile Behçet's disease in Taiwan.

BACKGROUNDS: Behçet's disease (BD) is a rare vasculitic disorder affecting all sizes of vessels. Among BD patients, 4 to 25% of patients with diagnosed age younger than 16 years old are defined as juvenile BD (JBD). This study aimed to evaluate the clinical manifestations and treatments of patients with JBD, with a particular focus on the effectiveness and safety of anti-tumor necrosis factor (TNF)-alpha therapy. METHODS: We retrospectively reviewed data of all patients diagnosed with JBD at age of 16 years or younger in a tertiary hospital in Taiwan. The clinical manifestations, laboratory data, treatments, disease courses, and clinical outcomes were evaluated. The effectiveness of anti-TNF-alpha therapy was measured based on changes in Behçet's Disease Current Activity Form (BDCAF) scores, prednisolone dosages and the immunosuppression load scores. RESULTS: Fifty-five patients were included in the study. The median age at disease onset was 11 years. The most common clinical presentation was recurrent oral aphthous ulcers (100%), followed by genital ulceration (69.1%), skin lesions (36.4%), gastrointestinal symptoms (29.1%), ocular involvement (27.3%), and arthralgia (27.3%). Ninety-one percent of the patients fulfilled the International Criteria for Behçet's Disease, and 36.4% met the Paediatric Behçet's Disease criteria. The most frequently used medications were prednisolone (74.5%) and colchicine (54.5%). Six patients with refractory or severe JBD received anti-TNF-alpha therapy. These patients were diagnosed at a younger age compared with those who did not receive anti-TNF-alpha therapy (7.5 vs 13 years; P = 0.012), the BDCAF scores reduced significantly at the 1st month, the 6th month and 1 year after the treatment. They did not use steroids after the first year of treatment, and, after treatment for 6 months, their immunosuppression load scores reduced significantly. Due to the limited case numbers, literature reviews of anti-TNF-alpha therapy for refractory JBD were conducted, which had a total 18 JBD patients receiving anti-TNF-alpha therapy, of which fifteen patients had favorable outcomes after treatment with minimal side effects. CONCLUSIONS: Anti-TNF-alpha therapy may be necessary for JBD patients with refractory disease courses. Anti-TNF-alpha therapy was effective and safe in these patients, especially regarding its corticosteroid- and immunosuppressive drug-sparing effects.

Chemokine MCP1/CCL2 and RANTES/CCL5 gene polymorphisms influence Henoch-Schönlein purpura susceptibility and severity.

BACKGROUND/PURPOSE: Henoch-Schönlein purpura (HSP) is the most common small vessel vasculitis in children. It is considered to be an IgA-containing immune complex-mediated disease. Chemokines are small secreted proteins that attract leukocytes during inflammation. Our aim was to determine the serum levels of chemokines and investigate the association of chemokine gene polymorphisms with childhood HSP. METHODS: Serum levels of chemokines (interleukin-8/CXCL8, MCP-1/CCL2, RANTES/CCL5, MIG/CXCL9, and IP-10/CXCL10) were determined using cytometric beads arrays. We investigated the association of three single-nucleotide polymorphisms (SNPs) MCP1/CCL2 -2518C/T, RANTES/CCL5 -403C/T, and RANTES/CCL5 -28C/G with HSP in 85 HSP patients and 136 healthy controls. RESULTS: Five serum chemokine levels were significantly elevated in patients with the acute stage of HSP compared to the normal controls (p < 0.05). MCP1/CCL2 -2518 TT genotype and T allele were associated with the risk for HSP with OR (95% CI) 3.32 (1.45-7.59) and 1.78 (1.20-2.64), respectively. The RANTES/CCL5 -28 GG genotype was associated with a significantly lower percentage of corticosteroid usage and lower corticosteroid accumulative dose in HSP patients. RANTES/CCL5 -403 TC and TT genotype were significantly associated with renal manifestations with an OR (95% CI) of 4.33 (1.44-12.99), adjusted for sex and age and the other two SNP genotypes. CONCLUSION: Our results support the fact that chemokines play important roles in the pathogenesis of HSP. MCP1/CCL2 gene polymorphisms were associated with susceptibility for HSP. RANTES/CCL5 gene polymorphisms may be related to disease severity and HSP nephritis.

Incidence of severe combined immunodeficiency through newborn screening in a Chinese population.

BACKGROUND/PURPOSE: In order to know the true incidence of severe combined immunodeficiency (SCID) in a Chinese population, we conducted and implemented SCID newborn screening in Taiwan. METHODS: Between May 1, 2010 and December 31, 2011, the National Taiwan University Hospital Newborn Screening Center screened all newborns for T-cell lymphopenia by measuring the copy number of T-cell receptor excision circles (TRECs) and RNase P. Newborns with low TREC values were subjected to complete blood cell counts and flow cytometry. RESULTS: A total of 106,391 newborns were screened using the TREC assay over a period of 19 months. Five newborns were immediately referred for confirmatory tests, including two SCID patients and two patients with persistent T-cell lymphopenia; a third SCID patient was found 2 months after the study period. All three SCID cases received stem cell transplantation at the age of 2-5 months. We also identified five cases of 22q11.2 microdeletion syndrome. During this period, two SCID patients from among the unscreened newborns were reported, and they died at ages 3 months and 4 months, respectively. CONCLUSION: Newborn screening to measure the number of TREC copies successfully identifies newborns with T-cell lymphopenia, 22q11.2 microdeletion syndrome, and other high-risk conditions. Taken together, the incidence of T-cell lymphopenia in apparently healthy newborns is more than 1 in 11,821, and further attention to their immune functions is warranted.

Clinical characteristics of children with positive anti-SSA/SSB antibodies.

This study aimed to characterize the manifestations of clinical symptoms and signs, primary rheumatic diseases, and other autoantibodies in pediatric patients with positive anti-SSA and/or anti-SSB antibodies. Subjects under age 18 with positive anti-SSA and/or anti-SSB antibodies were screened and enrolled in a tertiary hospital in Taiwan. Data were collected via medical records,including age, gender, onset of the primary rheumatic disease, clinical symptoms and signs, and the medication used. Schirmer test for Sjögren's syndrome (SS) screening was performed in all enrolled patients. Among twenty enrolled subjects, seventeen of them had systemic lupus erythematosus; four of them were diagnosed as SS with positive Schirmer test. In addition to antinuclear antibodies and anti-DNA antibodies, other common autoantibodies were anti-RNP antibodies (50 %) and anti-Sm antibodies(30 %). The most common symptoms were arthritis (60 %)followed by malar rash (40 %). In conclusion, we observed that a low proportion of childhood SS (4/20) exists in our patients with positive SSA and/or anti-SSB antibodies. It is suggested that clinicians should focus more on the clinical symptoms in these patients, rather than undertaking invasive diagnostic interventions to rule out Sjögren's syndrome.

Clinical characteristics and outcomes of primary antibody deficiency: a 20-year follow-up study.

BACKGROUND/PURPOSE: Primary antibody deficiency is the most common disorder among primary immunodeficiencies. Recurrent infection and chronic lung change often lead to mortality and morbidity. METHODS: This study focused on the clinical presentation, molecular diagnosis, and outcomes of primary antibody deficiency in Taiwan pediatric group. Medical records of patients with primary antibody deficiency during the period 1990-2010 were retrospectively reviewed in one medical center. RESULTS: Among the 34 patients evaluated, X-linked agammaglobulinemia (XLA) (29.4%) and common variable immunodeficiency diseases (CVIDs) (29.4%) were the most common disorders presented with respiratory and skin infections. Some genotype/phenotype discordance was found in one family. Patients with XLA, CVID, and hyper-IgM syndrome without complications had higher trough and initial IgG levels, and shorter delays in diagnosis. Patients with trough IgG levels >700 mg/dL had less occurrence of bronchiectasis. CONCLUSION: These results summarized clinical manifestations of primary antibody deficiency in pediatric group in Taiwan. Clinicians should strive to shorten delays in diagnosis and maintain higher trough IgG levels to decrease subsequent mortality and morbidity.

Rituximab as an effective add-on maintenance therapy for disease activities in childhood-onset systemic lupus erythematosus.

OBJECTIVES: Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease that can result in high morbidity if not treated. This retrospective study aimed to evaluate the outcomes of rituximab treatment in a paediatric SLE cohort in Taiwan. METHODS: The medical records of paediatric patients diagnosed with SLE at the National Taiwan University Hospital between January 1992 and August 2022 who received rituximab as maintenance therapy between January 2015 and August 2022 were retrospectively reviewed. To enhance our analysis, we included a contemporary comparison group, matching in case number and demographic characteristics. This study aimed to describe the indications, efficacy and safety of rituximab in the treatment of paediatric SLE and to analyse the factors associated with disease outcomes. RESULTS: The study included 40 rituximab-treated patients with a median age of 14.3 years at the time of disease diagnosis. In the rituximab-treated cohort, the median score on the Systemic Lupus Erythematosus Disease Activity Index 2000 decreased from 8 before rituximab administration to 4 after 2 years. The levels of C3 and C4 increased and anti-double stranded DNA (anti-dsDNA) levels decreased significantly within 6 months. The equivalent oral prednisolone dose halved after 6 months. Finally, 8 (20%) patients achieved disease control and 35 (87.5%) patients had no flare-ups during the follow-up period (median, 2 years). Those patients who achieved disease control had a significantly shorter interval between diagnosis and rituximab administration. In terms of adverse effects, only one patient developed hypogammaglobulinaemia that required intravenous immunoglobulin (IVIG) replacement. Compared with the comparison group (n=53), the rituximab-treated cohort exhibited superior disease outcomes and a reduced incidence of flare-ups. CONCLUSIONS: This study provides real-world data and illuminates rituximab's role in maintaining disease stability among patients with paediatric-onset SLE who are serologically active without major clinical deterioration. Most importantly, no mortality or development of end-stage renal disease was observed in the rituximab-treated cohort.

Peripheral blood cells RNA-seq identifies differentially expressed gene network linked to lymphocyte subsets alterations and active lupus nephritis associated with declines in renal function.

Background: The aim of this study was to investigate whether quantitative changes in lymphocyte subsets and gene expression in peripheral blood (PB) cells are related to the clinical manifestations and pathogenesis of lupus nephritis (LN). Methods: We enrolled 95 pediatric-onset SLE patients with renal involvement who presented with 450 clinical episodes suspicious for LN flare. Percentages of lymphocyte subsets at each episode were determined. We stratified 55 of 95 patients as high or low subset group according to the median percentage of each lymphocyte subset and the association with changes in the eGFR (ΔeGFR) were analyzed. Peripheral blood bulk RNA-seq to identify differentially expressed genes (DEGs) in 9 active LN vs. 9 inactive LN patients and the DEG-derived network was constructed by Ingenuity Pathway Analysis (IPA). Results: The mean ΔeGFR of low NK-low memory CD4+ T-high naive CD4+ T group (31.01 mL/min/1.73 m2) was significantly greater than that of high NK-high memory CD4+ T-low naive CD4+ T group (11.83 mL/min/1.73 m2; P = 0.0175). Kaplan-Meier analysis showed that the median time for ΔeGFR decline to mean ΔeGFR is approximately 10 years for high NK-high memory CD4+ T-low naive CD4+ T group and approximately 5 years for low NK-low memory CD4+ T-high naive CD4+ T group (log-rank test P = 0.0294). Conclusions: Our study highlighted important connections between DEG-derived network, lymphocyte subset composition, and disease status of LN and GN. A novel scoring system based on lymphocyte subset proportions effectively stratified patients into groups with differential risks for declining renal function.

Young children with Behçet disease have more intestinal involvement.

OBJECTIVE: Gastrointestinal (GI) involvement in childhood Behçet disease (BD) is not well understood. We aimed to clarify the intestinal presentation in children with BD. METHODS: Medical records of 85 children with recurrent oral ulcers between 1990 and 2010 at the National Taiwan University Hospital were reviewed retrospectively. Twenty of them who fulfilled the Mason and Barnes criteria for the diagnosis of childhood BD were enrolled. The clinical and laboratory characteristics were analyzed. RESULTS: Among 20 patients, the median age at diagnosis was 13.2 years. The common presentations included oral ulcers (100%), genital ulcers (70%), skin lesions (65%), and GI symptoms (50%). Five of 10 patients with GI symptoms received endoscopic examinations and all had ulcers. Divided by the age of 10, patients younger than 10 years tended to have higher rates of GI symptoms initially and intestinal ulcers (P = 0.002 and 0.015, respectively). Platelet count was significantly lower in young patients (P = 0.0151). Patients without GI symptoms had higher rates of skin involvement than patients with GI symptoms (P = 0.019). CONCLUSIONS: Young children with BD tended to have more GI presentations. For children with BD younger than 10 years having GI symptoms, endoscopic examinations may be considered.

Acute myocarditis and ventricular fibrillation as initial presentation of pediatric systemic lupus erythematosus.

Acute myocarditis and ventricular arrhythmia are rarely seen as the initial presentation of systemic lupus erythematosus (SLE) in children. We reported the case of a 12-year-old girl with congestive heart failure, acute myocarditis and pericardial effusion as a primary manifestation of SLE. Sudden cardiovascular collapse due to ventricular fibrillation (VF), ventricular tachycardia (VT) and cardiac tamponade occurred. After resuscitation and pericardiocentesis, frequent VF/VT refractory to anti-arrhythmic therapy was supported by venoarterial extracorporeal membrane oxygenation. Early diagnosis and a combination treatment for heart failure, arrhythmias and immunosuppression may result in a favorable outcome.

Respiratory-syncytial virus immunoprophylaxis on asthma symptoms development in prematurity with bronchopulmonary dysplasia.

Background: Infants with respiratory-syncytial virus bronchiolitis hospitalization are more likely to develop wheezing and subsequent asthma. Reportedly, palivizumab prophylaxis effectively prevents respiratory-syncytial virus hospitalization in high-risk children-such as premature infants or infants with bronchopulmonary dysplasia (BPD). Objective: We sought to explore the effect of respiratory-syncytial virus immunoprophylaxis on the risk of asthma development in premature infants with BPD in subtropical areas. Methods: This case-control study included preterm children with BPD born at Mackay Memorial Hospital, Taipei, Taiwan, from 1999 to 2015. Overall, medical records of 616 eligible participants were retrospectively collected from their birth to the time they attained an age of 5 to 20 years. The primary outcome was onset of active asthma. Results: Overall, 576 consecutive cases met the inclusion criteria. Of these, 306 (53.2%) patients had palivizumab exposure and 191 (33.2%) were diagnosed with asthma. Patients with history of respiratory-syncytial virus bronchiolitis hospitalization had a higher risk of developing asthma in the future (adjusted odds ratio, 3.77; 95% CI, 2.30-6.20, P < .001; hazard ratio, 2.56; 95% CI, 1.81-3.62, P < .001). Palivizumab prophylaxis reduced future asthma development through the inhibition of respiratory-syncytial virus bronchiolitis hospitalization (coefficient, -0.021; 95% CI, -0.031 to -0.011, P = .027). Asthmatic children who received palivizumab immunoprophylaxis had a lesser active asthma duration than those who did not (P = .005). Conclusions: Children with BPD with hospitalization for respiratory-syncytial virus bronchiolitis had higher risk of developing asthma compared with those without respiratory-syncytial virus infection. Prophylactic palivizumab might reduce later asthma development through inhibition of respiratory-syncytial virus bronchiolitis hospitalization. For those already developing asthma, palivizumab could reduce active asthma duration.

Differentially expressed microRNAs in peripheral blood cell are associated with downregulated expression of IgE in nonallergic childhood asthma.

Childhood asthma is a heterogeneous disease characterized by chronic airway inflammation, leading to a broad range of clinical presentations. Nonallergic asthma is asthma without allergic sensitization. Both clinical manifestations and immunopathological mechanisms of nonallergic childhood asthma were rarely investigated. We aimed to compare the clinical features between nonallergic and allergic childhood asthma and apply microRNA to explore the underlying mechanism of nonallergic childhood asthma. We enrolled 405 asthmatic children (76 nonallergic, 52 allergic with total IgE < 150 IU/mL and 277 allergic with total IgE > 150 IU/mL). Clinical characteristics were compared between groups. Comprehensive miRNA sequencing (RNA-seq) was performed using peripheral blood from 11 nonallergic and 11 allergic patients with elevated IgE, respectively. Differentially expressed miRNA (DEmiRNA) were determined with DESeq2. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis was performed to determine functional pathways involved. Publicly available mRNA expression data was applied to investigate the predicted target mRNA networks via Ingenuity Pathway Analysis (IPA). The average age of nonallergic asthma was significantly younger (5.614 ± 2.743 vs 6.676 ± 3.118 years-old). Higher severity and worse control were more common in nonallergic asthma (two-way ANOVA, P < 0.0001). Long-term severity was higher, and intermittent attacks persisted in nonallergic patients. We identified 140 top DEmiRNAs based on false discovery rate (FDR) q-value < 0.001. Forty predicted target mRNA gene were associated with nonallergic asthma. The enriched pathway based on GO included Wnt signaling pathway. IgE expression was predicted to be downregulated by a network involving simultaneous interaction with IL-4, activation of IL-10 and inhibition of FCER2. Nonallergic childhood asthma were distinct in their younger age, higher long-term severity and more persistent course. Differentially expressed miRNA signatures associate with downregulation of total IgE expression and predicted target mRNA genes related molecular networks contribute to canonical pathways of nonallergic childhood asthma. We demonstrated the negative role of miRNAs involved in regulating IgE expression indicating differences between asthma phenotypes. Identification of biomarkers of miRNAs could contribute to understand the molecular mechanism of endotypes in nonallergic childhood asthma, which can potentially allow delivery of precision medicine to pediatric asthma.

Risk factors for subsequent lupus nephritis in patients with juvenile-onset systemic lupus erythematosus: a retrospective cohort study.

BACKGROUND: Lupus nephritis (LN) is a crucial organ involvement in systemic lupus erythematosus (SLE). Patients with LN have higher morbidity and mortality rates than those without. Among all patients with LN, 20-40% had delayed onset, but the data for patients with juvenile-onset SLE (jSLE), who have a higher percentage of LN than patients with adult-onset SLE (aSLE), were limited. This study aimed to determine the risk factors for subsequent LN in patients with jSLE. METHODS: A retrospective cohort study was conducted between 2008 and 2018 in a single tertiary medical centre. Patients with diagnosed jSLE were reviewed. We investigated those without LN at diagnosis and whether they developed LN afterward. The primary outcome was the development of subsequent LN. Clinical manifestations at diagnosis, serial laboratory data, and treatments were reviewed during follow-up periods. RESULTS: Among the 48 patients with jSLE without initial LN, 20 developed subsequent LN later (Group 1), whereas 28 remained free of LN (Group 2). There was no difference in the percentage of initial manifestations except for more discoid rashes in Group 2 patients. In the Cox regression model, elevated average anti-double-stranded DNA (dsDNA) antibody, low average serum complements, and high average erythrocyte sedimentation rate (ESR) levels during follow-up were predictors of subsequent LN. After adjusting for these factors in multivariable analyses, only high average anti-dsDNA antibody and high average ESR levels remained predictive of subsequent LN. For every 100 IU/ml increase in anti-dsDNA antibody, the risk for subsequent LN in jSLE increases by 1.29 times (hazard ratio = 1.29, 95% confidence interval 1.055-1.573). CONCLUSION: Persistently high anti-dsDNA antibody and ESR levels during the follow-up period were risk factors for subsequent LN in patients with jSLE.

Clinical features and outcomes of patients with chronic granulomatous disease in Taiwan.

BACKGROUND: Chronic granulomatous disease (CGD) is a rare primary immunodeficiency disease characterized by defective neutrophil killing of microbial pathogens and recurrent infections. We aimed to investigate the clinical, genetic features, treatment, and outcomes in patients with CGD. METHODS: Pediatric patients diagnosed with CGD from a medical center in Taiwan were enrolled from January 1999 to Oct 2021. RESULTS: Nine pediatric patients with CGD were enrolled: six X-linked (XL) CGD with CYBB gene mutations, three autosomal recessive (AR) CGD with two NCF1 and one CYBA gene mutations. The median age of onset and age of diagnosis was 0.92 and 2.64 years, respectively. Patients with XL-CGD had a younger age of onset (4.6 months vs. 1.83 years, P = 0.06) and age of diagnosis (1.71 vs. 8.86 years, P = 0.024) than AR-CGD patients. The most common sites of infections were skin and soft tissue abscesses. The most common pathogens were Staphylococcus, Serratia, and Salmonella spp. Prophylactic antibiotics, anti-fungal agents, and interferon-gamma (IFN-γ) were given in 9 (100%), 7 (77.8%), and 8 (88.9%) patients, respectively. The mean duration of IFN-γ usage was 5.15 years. One male patient with XL-CGD was successfully treated with hematopoietic stem cell transplantation at 2.2 years. The mortality rate was 11.1%, and the estimated overall survival at 20 years was 66.7%. CONCLUSION: Staphylococcus aureus, Serratia marcescens, and Salmonella infections are important in Taiwanese CGD patients. Patients with XL-CGD have early disease onset. IFN-γ prophylaxis and prophylactic anti-microbial agents might have an effect on alleviating the infection episodes in CGD patients.

Association between human IL-10 gene polymorphisms and serum IL-10 level in patients with food allergy.

BACKGROUND/PURPOSE: Single nucleotide polymorphisms (SNPs) of the interleukin-10 (IL-10) gene are associated with allergic diseases in different populations. This study aimed to determine the distribution of two SNPs at -1082A/G and -592A/C (rs1800896 and rs1800872, respectively) in the IL-10 gene promoter of Taiwanese food allergy (FA) patients, and also to compare the serum IL-10 levels between patients with (FA) and controls. METHODS: Thirty-seven patients with FA and 52 controls were enrolled, and their peripheral blood was collected for IL-10 SNP genotyping and the corresponding serum IL-10 level of each genotype. RESULTS: The thirty-seven FA patients had positive food-specific IgE (≥ 0.75kU/L) to more than one food, and the most frequent allergens wereshrimp and crab (56.8% and 35.1%, respectively). The genotype distributions in the FA patients compared to the control group were AA and AG at -1082A/G (86.5% and 13.5% vs. 86.6% and 13.4%, respectively), and AA, AC, and CC at -592A/C (45.9%, 43.3% and 10.8% vs. 38.5%, 48.1% and 13.4%, respectively). Serum IL-10 levels were significantly lower in the FA group than in the control group (p=0.0187), and the IL-10 level of -592A/C of genotype AA was significantly lower than that of the other genotypes (AC+CC) (p=0.007). Patients with AA/AA haplotype homozygotes (10 of 24) had significantly lower serum IL-10 levels than those with other haplotypes. CONCLUSIONS: The two SNPs at -1082A/G and -592A/C of IL-10 were associated with FA in our Taiwanese population, and FA patients with the genotype AA/AA haplotype homozygotes had lower serum IL-10 levels. This suggests that IL-10 might play a critical role in the pathogenesis of FA. We suggest that it may be practicable to evaluate the serum IL-10 levels of FA patients and to predict the possibility of FA if genotypes and haplotypes are checked regularly.

Initial manifestations and clinical course of systemic onset juvenile idiopathic arthritis: a ten-year retrospective study.

BACKGROUND/PURPOSE: The diagnosis of systemic onset juvenile idiopathic arthritis (SoJIA) on disease onset is challenging and made mainly by exclusion. This study aimed to investigate the initial clinical and laboratory features of children with SoJIA in Taiwan. METHODS: Patients diagnosed with SoJIA at the National Taiwan University Hospital between 1997 and 2007 were evaluated and data were collected by retrospective chart review. Inferential statistics were used to compare features of patients with steroid use for <6 months or >6 months. RESULTS: Twenty-eight (28) patients (13 boys and 15 girls) were included in this study. The mean age of onset was 8.7 years old. The most common presentations were fever (100%), arthritis (89.3%), and skin rash (67.9%). The patterns of arthritis in affected patients were 50% oligoarticular type and 39% polyarticular type. The most common joints involved were the knee (76% of patients with arthritis), ankle (56%), and elbow and proximal interphalangeal joints (28%). The most common pattern of fever during first week was intermittent (53%). Prolonged use of steroid was associated with leukocytosis (17.63±7.71 vs. 11.93±4.43×10(9) leukocytes/L, p<0.05) and higher aspartate aminotransferase (89.4 vs. 31.2 U/L, p<0.05) on initial presentation. CONCLUSION: In SoJIA, extra-articular features such as fever, rash, and lymphadenopathy are most prominent. Leukocytosis and polyarticular pattern on presentation may indicate a refractory clinical course.