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Biomedical subjects

Alan P Knutsen

Publications and source records attributed to Alan P Knutsen.

9 recordsLinked to original sources
PubMed2006

Specific antibodies to recombinant allergens of Aspergillus fumigatus in cystic fibrosis patients with ABPA.

BACKGROUND: Aspergillus fumigatus, a widely distributed fungus, has been implicated in causing life threatening infections as well as severe asthma and allergic diseases in man. Allergic affliction like allergic bronchopulmonary aspergillosis (ABPA) is a disabling lung disease frequently seen in patients with asthma and cystic fibrosis. Immunodiagnosis of the former is comparatively easier due to the availability of purified antigens and sensitive methods. However, this is not true with cystic fibrosis patients where the prevalence of ABPA is fairly high and the morbidity and mortality are significant. METHODS: In the present study, we have evaluated purified recombinant allergens from A. fumigatus, namely Asp f 1, f 2, f 3, f 4, and f 6 using ELISA and a semi-automated method (ImmunoCAP). We studied 17 patients each from cystic fibrosis with ABPA, and cystic fibrosis with asthma, 22 cystic fibrosis with no ABPA or asthma, and 11 age matched controls. RESULTS: The results indicate that no antigen, antibody or method is capable of differentiating cystic fibrosis (CF) with ABPA from other CF patients, although some allergens showed strong reaction or showed more prevalence among the patients studied. CONCLUSION: When results of several allergens such as Asp f 1, f 2, f 3, f 4, and f 6 in their binding to IgA, IgG, and IgE antibodies were analyzed, a more strong discrimination of CF patients with ABPA was possible from the other groups studied.

Journal Article↗
PubMed2006

IL-4 alpha chain receptor (IL-4Ralpha) polymorphisms in allergic bronchopulmonary sspergillosis.

BACKGROUND: Allergic bronchopulmonary aspergillosis occurs in 7-10% of cystic fibrosis (CF) and 1-2% of asthmatic patients. HLA-DR restriction and increased sensitivity to IL-4 stimulation have been proposed as risk factors in these populations. OBJECTIVE: We examined for the presence of IL-4 receptor alpha chain (IL-4Ralpha) single nucleotide polymorphisms (SNPs) in ABPA and whether these accounted for increased sensitivity to IL-4 stimulation. METHODS: One extracellular (ile75val) and four cytoplasmic IL-4Ralpha SNPs were analyzed in 40 CF and 22 asthmatic patients and in 56 non-ABPA CF and asthmatic patients. Sensitivity to IL-4 stimulation was measured by induction of CD23 expression on B cells. RESULTS: IL-4Ralpha SNPs were observed in 95% of ABPA patients. The predominant IL-4Ralpha SNP was the extracellular IL-4Ralpha SNP, ile75val, observed in 80% of ABPA patients. CONCLUSION: The presence of IL-4Ralpha SNPs, principally ile75val, appears to be a genetic risk for the development of ABPA.

Journal Article↗
PubMed2005

Use of rituximab to decrease panel-reactive antibodies.

Patients with pre-formed antibodies may be at increased risk of rejection after organ transplantation. In this report, we describe the use of rituximab to decrease the percentage of pre-formed antibodies in a pediatric heart transplant recipient.

Antibodies↗
PubMed2005

Allergic bronchopulmonary aspergillosis in a patient with cystic fibrosis: diagnostic criteria when the IgE level is less than 500 IU/mL.

BACKGROUND: Recently, the Cystic Fibrosis Foundation developed a consensus report recommending diagnostic criteria for allergic bronchopulmonary aspergillosis (ABPA) in patients with cystic fibrosis that includes a serum IgE level greater than 500 IU/mL as the "minimal diagnostic criterion." OBJECTIVE: To describe a 7-year-old girl with ABPA whose serum IgE level increased to only 398 IU/mL. METHODS: Total IgE and anti-Aspergillus serologic measurements were performed using enzyme-linked immunosorbent assay and standard laboratory techniques; HLA analysis was performed; interleukin 4 receptor alpha single nucleotide polymorphisms were performed using polymerase chain reaction and DNA sequencing; CD23+ B cells were measured using flow cytometry; and cytokine synthesis to Aspergillus purified antigens was assessed using flow cytometry. RESULTS: A 7-year-old girl with cystic fibrosis who had mild pulmonary disease and well-controlled asthma developed pulmonary infiltrates, increased wheezing, and decreased pulmonary function. Additional studies demonstrated peripheral blood eosinophilia (eosinophil count, 1807 cells/mm3 [19%]) and an increase in IgE and IgG anti-Aspergillus serology; bronchoalveolar lavage revealed septate hyphae with 45 degrees branching subsequently identified as A fumigatus and pulmonary eosinophilia. Previous HLA typing revealed that the patient was HLA-DR2+, DRB*1501, HLA-DQ2-, a pattern associated with increased risk of ABPA. In addition, there was increased up-regulation of CD23 molecules by interleukin 4 stimulation on the patient's B cells, as observed in ABPA. The patient was treated with corticosteroids and itraconazole with resolution of symptoms and pulmonary infiltrates. CONCLUSIONS: Examination of the pulmonary inflammatory response using bronchoalveolar lavage, genetic risk with HLA-DR2+DQ2- typing, and increased interleukin 4 sensitivity are useful adjunctive studies in the diagnosis of ABPA.

Aspergillosis, Allergic Bronchopulmonary↗
PubMed2004

Rice-induced enterocolitis in an infant: TH1/TH2 cellular hypersensitivity and absent IgE reactivity.

BACKGROUND: Although food allergy is common in children, rice allergy is unusual in Western cultures. OBJECTIVE: To report a case of T-cell-mediated rice intolerance in an 11-month-old girl. METHODS: To evaluate the intolerance to rice in this patient, a graded rice food challenge was performed. To examine the immunologic reactivity to rice, in vitro lymphoproliferative responses and cytokine synthesis of rice-stimulated peripheral blood lymphocytes (PBLs) was performed. Subsequently, skin patch testing to rice and other foods was performed. RESULTS: Allergy skin prick test results were negative for rice and positive for egg, milk, and soy. Specific IgE antibodies to rice, egg, peanut, wheat, walnut, codfish, milk, soybean, corn, shrimp, scallops, and clams were undetectable. Results of a single-blind rice food challenge were positive, manifested by emesis that persisted for more than an hour and required intravenous hydration. In vitro lymphoproliferation by the patient's PBLs to rice stimulation was positive. In addition, cytokine synthesis of interferon-gamma, interleukin 10 (IL-10), tumor necrosis factor a, and IL-5 by the patient's rice-stimulated PBLs was elevated, indicating a TH1/TH2 cell response to rice. Endoscopy revealed normal esophageal, gastric, and duodenal mucosa; a biopsy specimen revealed mild esophagitis. Duodenal explant T cells were initially established by stimulation with rice and IL-2. After a 2-day rest, the lymphocytes were restimulated with rice for 7 days and revealed increased interferon-gamma and IL-5 synthesis. Twenty billion colony forming units of Lactobacillus GG were added to the patient's diet twice daily. After 6 weeks, rice rechallenge resulted in emesis within 1 hour. Results of patch testing were positive to rice, wheat, and barley but negative to soy, which the patient tolerated on food challenge. CONCLUSIONS: Although this patient did not demonstrate IgE antibody to rice, TH1/TH2 cell-mediated responses to rice were detected, and the patient experienced significant morbidity. Patch testing for gastrointestinal food allergies may be useful when the food specific IgE antibody is negative. Probiotic therapy in this patient did not ameliorate her sensitivity to rice, and food elimination remains the only reliable treatment for TH1/TH2-mediated food hypersensitivity.

Enterocolitis↗
PubMed2003

Allergic bronchopulmonary aspergillosis in cystic fibrosis--state of the art: Cystic Fibrosis Foundation Consensus Conference.

Because of the difficulties of recognizing allergic bronchopulmonary aspergillosis (ABPA) in the context of cystic fibrosis (because of overlapping clinical, radiographic, microbiologic, and immunologic features), advances in our understanding of the pathogenesis of allergic aspergillosis, new possibilities in therapy, and the need for agreed-upon definitions, an international consensus conference was convened. Areas addressed included fungal biology, immunopathogenesis, insights from animal models, diagnostic criteria, epidemiology, the use of new immunologic and genetic techniques in diagnosis, imaging modalities, pharmacology, and treatment approaches. Evidence from the existing literature was graded, and the consensus views were synthesized into this document and recirculated for affirmation. Virulence factors in Aspergillus that could aggravate these diseases, and particularly immunogenetic factors that could predispose persons to ABPA, were identified. New information has come from transgenic animals and recombinant fungal and host molecules. Diagnostic criteria that could provide a framework for monitoring were adopted, and helpful imaging features were identified. New possibilities in therapy produced plans for managing diverse clinical presentations.

Animals↗
PubMed2003

Lymphocytes in allergic bronchopulmonary aspergillosis.

Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity lung disease mediated by an allergic late-phase inflammatory response to Aspergillus fumigatus antigens. ABPA is characterized by markedly elevated Aspergillus-specific and total IgE levels and eosinophilia, and manifested by wheezing, pulmonary infiltrates and bronchiectasis and fibrosis, which affect asthmatic and cystic fibrosis (CF) patients. In the pathogenesis of ABPA, A. fumigatus proteases play a role in facilitation of antigen transport across the epithelial cell layer by damaging the epithelial integrity and by a direct interaction with epithelial cell surface receptors, resulting in pro-inflammatory cytokine production and corresponding inflammatory responses. In genetically susceptible asthmatic and CF patients, this leads to an allergic inflammatory response to Aspergillus allergens. A genetic susceptibility is HLA-DR restriction demonstrated by increased frequency of HLA-DR2 and/or DR5 and lack HLA-DQ2. IL-4 plays a central role in the development of allergic inflammatory responses. Our group has demonstrated that ABPA patients have increased sensitivity to IL-4 stimulation and skewing of Th2 responses to Aspergillus allergens in ABPA subjects and a Th1 response in non-ABPA subjects. Interestingly, Aspergillus allergens stimulate IL-10 synthesis is both ABPA and non-ABPA subjects.

Animals↗
PubMed2003

Umbilical cord blood transplantation in Wiskott Aldrich syndrome.

OBJECTIVE: To report the use of umbilical cord blood (UCB) stem cell transplantation in Wiskott Aldrich syndrome (WAS) when a matched sibling donor was unavailable. METHODS: Three children with WAS received unrelated umbilical cord blood stem cell transplantation after a preparative regimen for the treatment of combined immunodeficiency diseases. The patients ranged in age from 1.9 to 7.9 years. The cord blood units were 4/6 HLA antigen matches in 2 children and 5/6 in 1 child, with molecular HLA-DR match in all 3 children. RESULTS: The time for neutrophil engraftment (ANC >500/mm(3)) was 11 to 16 days, and the average time for platelet engraftment was 36 to 49 days. One patient had no evidence of GvHD, 1 patient grade I, and 1 patient grade II. No patient had chronic GvHD. The patient with grade II GvHD also had gut involvement. Immunologic reconstitution demonstrated that cord blood stem cell transplantation resulted in consistent and stable T-, B-, and NK-cell development. Functional B-cell antibody responses revealed that 2 of the patients in whom IVIG has been discontinued had low detectable antibody responses to tetanus and diphtheria toxoid immunizations at 18 to 24 months after transplantation. CONCLUSIONS: Unrelated umbilical donor cord blood is an alternative source of stem cells for transplantation in children with WAS when a suitable HLA-matched donor is not available. Benefits of UCB include rapid and reliable recovery of immune function, low risk of GvHD, and low viral transmission rate.

Antibodies, Bacterial↗
PubMed2002

Immunopathogenesis of allergic bronchopulmonary aspergillosis in cystic fibrosis.

Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity lung disease mediated by an allergic late-phase inflammatory response to Aspergillus fumigatus antigens. ABPA is characterized by markedly elevated Aspergillus-specific and total IgE levels and eosinophilia, and manifested by wheezing, pulmonary infiltrates, and bronchiectasis and fibrosis, which afflict asthmatic and cystic fibrosis (CF) patients. We propose that ABPA develops in genetically susceptible CF patients due to HLA-DR2 and DR5 restriction, increased sensitivity to IL-4 stimulation, and increased A. fumigatus allergen-specific Th2 CD4+ T-cell-mediated responses. In addition, A. fumigatus proteases play a role in facilitation of antigen transport across the epithelial cell layer by damaging the epithelial integrity and by a direct interaction with epithelial cell surface receptors, resulting in pro-inflammatory cytokine production and corresponding inflammatory responses.

Antibodies, Fungal↗