Han-Jung Park

Association between polymorphisms in prostanoid receptor genes and aspirin-intolerant asthma.

Background Genetic predisposition is linked to the pathogenesis of aspirin-intolerant asthma. Most candidate gene approaches have focused on leukotriene-related pathways, whereas there have been relatively few studies evaluating the effects of polymorphisms in prostanoid receptor genes on the development of aspirin-intolerant asthma. Therefore, we investigated the potential association between prostanoid receptor gene polymorphisms and the aspirin-intolerant asthma phenotype. Methods We screened for genetic variations in the prostanoid receptor genes PTGER1, PTGER2, PTGER3, PTGER4, PTGDR, PTGIR, PTGFR, and TBXA2R using direct sequencing, and selected 32 tagging single nucleotide polymorphisms among the 77 polymorphisms with frequencies >0.02 based on linkage disequilibrium for genotyping. We compared the genotype distributions and allele frequencies of three participant groups (108 patients with aspirin-intolerant asthma, 93 patients with aspirin-tolerant asthma, and 140 normal controls). Results Through association analyses studies of the 32 single nucleotide polymorphisms, the following single nucleotide polymorphisms were found to have significant associations with the aspirin-intolerant asthma phenotype: −616C>G (P=0.038) and −166G>A (P=0.023) in PTGER2; −1709T>A (P=0.043) in PTGER3; −1254A>G (P=0.018) in PTGER4; 1915T>C (P=0.015) in PTGIR; and −4684C>T (P=0.027), and 795T>C (P=0.032) in TBXA2R. In the haplotype analysis of each gene, the frequency of PTGIR ht3[G-G-C-C], which includes 1915T>C, differed significantly between the aspirin-intolerant asthma patients and aspirin-tolerant asthma patients (P=0.015). Conclusion These findings suggest that genetic polymorphisms in PTGER2, PTGER3, PTGER4, PTGIR, and TBXA2R play important roles in the pathogenesis of aspirin-intolerant asthma.

Diagnostic value of the serum-specific IgE ratio of ω-5 gliadin to wheat in adult patients with wheat-induced anaphylaxis.

Background: Wheat is an important food allergen associated with severe allergic reactions, including wheat-dependent exercise-induced anaphylaxis (WDEIA) and wheat-induced anaphylaxis (WIA). To diagnose WDEIA, an exercise challenge test following wheat ingestion is performed, which is time-consuming and unsafe. The compound ω-5 gliadin has been identified as a major allergen for WDEIA and WIA. We evaluated the diagnostic value of serum immunoglobulin E (IgE) ratios of ω-5 gliadin to wheat in adult patients with WDEIA or WIA. Methods: In total, 27 patients were enrolled and classified into 2 groups according to the severity of their allergic reactions to wheat. Serum IgE, specific to wheat and ω-5 gliadin, was measured using the ImmunoCAP system. To evaluate the diagnostic value, receiver operator characteristic curves were produced. Results: Group 1 included 17 patients with a history of anaphylaxis and group 2 included 10 patients having urticaria or atopic dermatitis. Serum IgE specific to wheat was increased in 47% of group 1 and 100% of group 2. However, all patients in group 1 had high serum IgE specific to ω-5 gliadin, whereas only 20% of group 2 showed increased levels. To identify a better diagnostic value, the log-transformed IgE ratio of ω-5 gliadin to wheat was calculated, with the cutoff value at 0.3. Based on these criteria, we found 100% sensitivity and specificity. Conclusions: This study confirms that the serum IgE ratio of ω-5 gliadin to wheat may be a useful marker for the diagnosis of WDEIA and WIA.

Differential Contribution of the CysLTR1 Gene in Patients with Aspirin Hypersensitivity

In this study, we compared the roles of CysLT receptor type 1 (CysLTR1) and leukotriene C4 synthase (LTC4S) gene polymorphisms in two major aspirin-related allergic diseases, aspirin-intolerant asthma (AIA) and aspirin-induced chronic urticaria/angioedema (AICU). CysLTR1-634C>T and LTC4S-444A>C polymorphisms were genotyped and its functional effect on the promoter activity was compared. As in vivo functional study, changes of peripheral mRNA level of CysLTR1 were measured by real-time PCR before and after aspirin challenge. A significant association was found for the CysLTR1 promoter polymorphism and the AIA phenotype compared to AICU (P = 0.015). In U937 cells, the variant genotype reporter construct showed significantly higher promoter activity than the common genotype (P < 0.05). The CysLTR1 mRNA levels increased significantly after aspirin challenge in AIA patients (P = 0.013). In conclusion, the CysLTR1 polymorphism may contribute to develop to the AIA phenotype and be used as a genetic marker for differentiating two major aspirin hypersensitivity phenotypes.

Treatment of Atopic Dermatitis with a Combination of Allergen-Specific Immunotherapy and a Histamine-Immunoglobulin Complex

Background: Allergic responses to common environmental agents are believed to be involved in the development of atopic dermatitis, but clinical usefulness of allergen-specific immunotherapy in the treatment of atopic dermatitis is controversial. We performed a pilot study to evaluate the clinical usefulness of combined treatment with allergen-specific immunotherapy and a histamine-immunoglobulin complex in patients with atopic dermatitis. Methods: Twenty patients with atopic dermatitis and hypersensitivity to house dust mites whose clinical conditions had not been effectively controlled by current standard medical therapies were treated with a combination of allergen-specific immunotherapy using house dust mite extract and a histamine-immunoglobulin complex for 12 months. The primary efficacy outcome was the change in the standardized clinical severity scoring system for atopic dermatitis (SCORAD) values at 6 and 12 months in comparison with the values at baseline. Results: In 18 patients who completed all 12 months of treatment, the SCORAD values significantly decreased from 43.6 ± 15.9 at baseline to 27.8 ± 18.3 at 6 months and 18.3 ± 14.9 at 12 months (Wilcoxon signed-rank test, p < 0.001), and no significant systemic side effects were observed. Conclusions: In this uncontrolled pilot study, combined treatment with allergen-specific immunotherapy and a histamine-immunoglobulin complex resulted in significant clinical improvements in patients with atopic dermatitis. However, double-blind placebo-controlled studies are necessary to test the clinical usefulness of this modified allergen-specific immunotherapy for atopic dermatitis.

Immunoglobulin G Subclass Deficiency is the Major Phenotype of Primary Immunodeficiency in a Korean Adult Cohort

Primary immunodeficiency disease (PID) is a rare disorder in adults. Most often, serious forms are detected during infancy or childhood. However, mild forms of PID may not be diagnosed until later in life, and some types of humoral immunodeficiency may occur in adulthood. The purpose of this study was to identify clinical features of PID in Korean adults. A retrospective study was performed on 55 adult patients who were diagnosed as PID between January 1998 and January 2009 at a single tertiary medical center in Korea. IgG subclass deficiency was the most common phenotype (67%, 37/55), followed by total IgG deficiency (20%, 11/55), IgM deficiency (7%, 4/55), common variable immunodeficiency (2%, 1/55), and X-linked agammaglobulinemia (2%, 1/55). IgG3 and IgG4 were the most affected subclasses. Upper and lower respiratory tract infections (76%) were the most frequently observed symptoms, followed by multiple site infection (11%), urinary tract infection, and colitis. Bronchial asthma, rhinitis, and several autoimmune diseases were common associated diseases. IgG and IgG subclass deficiency should be considered in adult patients presenting with recurrent upper and lower respiratory infections, particularly in those with respiratory allergies or autoimmune diseases.

Drug‐specific CD4+ T‐cell immune responses are responsible for antituberculosis drug‐induced maculopapular exanthema and drug reaction with eosinophilia and systemic symptoms syndrome

A multidrug regimen including isoniazid, rifampicin, pyrazinamide and ethambutol is commonly used as first‐line treatment for tuberculosis. However, this regimen can occasionally result in severe adverse drug reactions, such as drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome and drug‐induced liver injury. The culprit drug and mechanistic basis for the hypersensitive reaction are unknown.

An Antinuclear Antibody-Negative Patient With Lupus Nephritis

Systemic lupus erythematosus (SLE) is a typical autoimmune disease thats characterized by various autoantibodies to nuclear and cytoplasmic antigens. The presence of antinuclear antibodies (ANA) in serum is generally considered a decisive diagnostic sign of SLE. However, a small subset of SLE patients who had the typical clinical features of SLE was reported to show persistently negative ANA tests. Our report describes a 16-yr-old female who presented with the clinical manifestations of SLE such as malar rash, photosensitivity, arthritis, lymphopenia, pericarditis and proteinuria. The serum autoantibodies were all negative and renal biopsy showed that the histopathological changes of immune complex mediated the focal segmental necrotizing glomerulonephritis with crescent formation. She was treated with monthly pulse cyclophosphamide along with corticosteroids. During the 2-yr follow-up period, the proteinuria was markedly decreased and all of the ANA and anti-double stranded DNA antibody tests were negative. This case suggests that ANA may not be required in the pathogenesis of lupus nephritis.

Successful treatment of pediatric systemic polyarteritis nodosa with cholestatic hepatitis

Polyarteritis nodosa (PAN) is a rare vasculitis in children. We report a case of 5-year-old boy with systemic PAN and cholestatic hepatitis. He had fever, abdominal pain, and gastrointestinal bleeding. Angiography revealed multiple microaneurysms in the renal, hepatic, and superior mesenteric arteries. Clinical manifestations improved slowly after immunosuppressive therapy, but liver enzyme and bilirubin levels elevated gradually. Liver biopsy findings revealed marked centrizonal canalicular cholestasis, bile duct damage, and intact hepatocyte, but there was no evidence of viral hepatitis or vasculitis. Levels of liver enzymes and bilirubin improved after two cycles of cyclophosphamide therapy. We thought that the possible etiology of elevated liver enzyme and bilirubin levels might be a manifestation of PAN.