Patricia S. Hutcheson

IgE antibody to Aspergillus fumigatus recombinant allergens in cystic fibrosis patients with allergic bronchopulmonary aspergillosis

Background:  Allergic bronchopulmonary aspergillosis (ABPA) in cystic fibrosis (CF) is characterized by a heightened Th2 CD4+ T‐cell response to Aspergillus fumigatus (Af) allergens and a hyper‐immunoglobulin E (IgE) state compared with cystic fibrosis patients without ABPA. The IgE serologic differentiation of ABPA from atopic CF patients can be difficult. We propose as the reactivity with purified antigens varies qualitatively and quantitatively and that the antibody response is more specific than with crude Af antigen extract, the IgE responses to purified recombinant Af allergens may differentiate ABPA from atopic CF patients.

Variability in parameters of allergic bronchopulmonary aspergillosis in patients with cystic fibrosis

Seventy-nine patients with cystic fibrosis (CF) were evaluated and were followed in a longitudinal, prospective fashion during a 6-year period for the development of immune parameters indicating Aspergillus fumigatus (Af) sensitization and allergic bronchopulmonary aspergillosis (ABPA). Although four patients developed frank ABPA, there was considerable variability in immune parameters in non-ABPA. Twenty-four patients became skin test positive to Af with none losing skin reactivity. Twenty-five patients developed serum precipitins to Af, whereas 12 patients lost their precipitins. Of 15 patients with an elevated total serum IgE of greater than or equal to 2 SD, five demonstrated a marked decline of at least 40%. Three of 16 patients with IgE-Af became negative, whereas eight of 27 patients lost their IgG-Af. None of these patients had received corticosteroid therapy that could have accounted for the findings. Thus, patients with CF frequently lose evidence of Af sensitivity spontaneously without corticosteroid intervention. The diagnosis of ABPA in CF should not be based solely on serology and skin test results, since at any point in time, patients with CF may demonstrate variable responses to Af.

Aspergillus fumigatus spore concentration in outside air: Cardiff and St Louis compared

Intermittent sampling of the atmosphere 3 days/week over a 12‐month period using Andersen samplers in Cardiff, Wales, U.K. and St Louis, Missouri, U.S.A., indicated average A. fumigatus spore concentrations of 13.5/m3 in St Louis and 11.3/m3 in Cardiff. Both sites showed seasonal variations with highest concentrations during winter.

Distinctions between allergic fungal rhinosinusitis and chronic rhinosinusitis.

Background Recent reports have attempted to redefine the accepted diagnostic criteria for allergic fungal rhinosinusitis (AFRS), a form of chronic rhinosinusitis (CRS) with nasal polyps. As a result, the existence of AFRS as a distinct entity has been questioned, suggesting that allergy has no role in CRS with sinonasal eosinophilia, and the condition should be referred to as eosinophilic fungal rhinosinusitis. The purpose of the study was to differentiate between AFRS and CRS by studying antibody responses in these two clearly defined patient groups. Methods Ninety-nine patients were enrolled and classified as AFRS or CRS (without AFRS). Serum total IgE, IgG anti–Alternaria-specific antibodies (UniCAP 100), and IgE antifungal antibodies (immunoblotting) were compared between the groups. Results Sixty-four patients fit the traditional criteria for AFRS, with 35 as CRS. Mean serum total IgE and mean IgG anti–Alternaria-specific antibodies were statistically significantly increased in AFRS over CRS patients. There was also a statistically significant increase in the mean number of IgE antifungal bands from AFRS compared with CRS patients. Conclusion We have shown a clear immunologic difference between AFRS and CRS patients. The overwhelming evidence of increased total IgE and fungal-specific IgE in AFRS supports an allergic component in AFRS. IgG anti–Alternaria-specific antibodies also point to an exaggerated fungal immune response in these patients. These results support the existence of AFRS as a separate, distinct entity of CRS. It is important to recognize AFRS to ensure proper treatment in these patients.

Serum anti-Aspergillus fumigatus antibodies by immunoblot and ELISA in cystic fibrosis with allergic bronchopulmonary aspergillosis☆

Allergic bronchopulmonary aspergillosis (ABPA) occurs with a prevalence of 5% to 15% in patients with cystic fibrosis (CF). Because of the frequent colonization with Aspergillus fumigatus (Af) in CF, the causative agent of ABPA, antibody reactivity to Af proteins is frequently observed, which obscures the diagnosis of ABPA. Patients with CF are also categorized according to the presence of positive skin test responses to Af and/or the presence of positive precipitins. In this study we used ELISA and immunoblot assay to detect IgE and IgG anti-Af antibodies in patients with CF and ABPA (n = 13) compared with other groups of patients with CF: those with positive skin test and positive precipitin results (n = 18), those with positive skin test and negative precipitin results (n = 14), those with negative skin test and positive precipitin results (n = 10), and those with negative skin test and negative precipitin results (n = 35). IgE and IgG anti-Af antibodies were significantly elevated in patients with ABPA as determined by both immunoblot assay (p < 0.01) and ELISA (p < 0.01). However, detection of Af antibodies by ELISA was more sensitive in discriminating patients with CF and ABPA from patients with CF who had positive skin test and positive precipitin results but lacked radiographic and clinical evidence of ABPA. In patients with CF and ABPA the immunoblot assays demonstrated a multitude of IgE, IgG, and IgA antibody responses to Af proteins, which ranged in molecular weight from 14 kd to greater than 106 kd. The level of IgE anti-Af antibody to individual proteins decreased during remissions of ABPA.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of intradermal skin tests in the evaluation of clinically relevant respiratory allergy assessed using patient history and nasal challenges

BACKGROUND Skin testing, correlated with patient history, is the accepted method of identifying clinically relevant aeroallergen sensitivity. Traditionally, intradermal tests are believed to be more sensitive in identifying aeroallergen sensitivity than the epicutaneous and percutaneous methods. Therefore, many allergy practitioners use the epicutaneous or percutaneous method first and, if the results are negative, follow up with intradermal tests. OBJECTIVES To compare the epicutaneous, percutaneous, and intradermal methods to determine their sensitivity to patient history and to evaluate the value of intradermal tests when epicutaneous and percutaneous test results are negative. METHODS Participants were evaluated for rhinoconjunctivitis symptoms and then were skin tested using the prick and Multi-Test II (MTII) methods. Intradermal tests were performed when prick and MTII test results were negative to an aeroallergen. Participants with negative prick and MTII test results and corresponding positive intradermal test results underwent nasal challenges with evaluation by anterior rhinomanometry. RESULTS Compared with patient history, average sensitivity for MTII was 77% and for the prick method was 62%. When MTII results were negative, 17% of intradermal tests corresponded with probable patient histories of allergy but none with positive nasal challenge results. Nasal challenge results were similar to those of the negative control group and significantly different from those of the positive control group (P < .001). CONCLUSIONS The MTII tests are more sensitive and equally specific compared with the prick method. When MTII results are negative, positive intradermal test results are unlikely to identify clinically relevant aeroallergen sensitivity. Routine performance of intradermal tests when MTII results are negative is likely to be of low clinical yield.

Primary paranasal aspergillus granuloma: Case report and review of the literature

Background Primary paranasal aspergillus granuloma (PPAG) is a slowly progressive chronic infection of the sinus extending beyond the confines of the sinus. It has been reported only in patients from the Sudan and India. Microscopically, it differs from chronic invasive fungal sinusitis in that there are pseudotubercles containing giant cells, histiocytes, lymphocytes, plasma cells, newly formed capillaries, eosinophils, and Aspergillus fungal elements. Conclusion We describe the first case of PPAG in the United States in an immunocompetent nonatopic woman who had never left Missouri.

Immune response in experimentally induced uremia: I. Suppression of mitogen responses by adherent cells in chronic uremia

Abstract The response of spleen cells to T-cell mitogens PHA-P and Con A and to the B-cell mitogen LPS was studied in experimentally induced chronic uremia. The activity of spleen cells from chronic uremic rats to mitogens was shown to be significantly suppressed as compared to that of cells from control animals. This suppression appears to be mediated by suppressor cells which can be eliminated by adherence to glass wool and rayon wool. Also, the addition of plastic-adherent cells to nonadherent cell population restores the suppressed response to mitogens. Thus, the suppressed response of uremic spleen cells to mitogens seems to result from a suppressor cell activity which is present in experimentally induced chronic uremia and which is more potent than the naturally occurring suppressor cell in control rats.

T-cell receptor bias in patients with allergic bronchopulmonary aspergillosis.

CD4(+) Th2 helper cell mediated immune responses have been shown to play a crucial role in the pathogenesis of ABPA. HLA and TCR are the candidate genes, which can influence the specificity of these responses. We have previously established a strong association of HLA DR2/5 in ABPA susceptibility. The study was designed to determine whether allergen specific T cell express a limited usage of T cell receptor (TCR) Vbeta gene repertoire in ABPA and to find an association of susceptible HLA-DR determinants with the identified TCR gene segments. TCR Vbeta typing was performed on antigen specific T cell lines from 14 ABPA and 12 nonABPA patients. The majority of ABPA patients (86%) expressed allergen specific T cells with Vbeta13 genes indicating its role in susceptibility, whereas in nonABPA controls, Vbeta1 genes T cell repertoires were predominantly expressed. The unrestricted pattern of Vbeta gene amplification seen before antigen stimulation suggests an oligoclonal expansion of a specific T cell population in response to the allergen Asp f 1 in ABPA and nonABPA patients. The increased usage of Vbeta13 in ABPA and Vbeta1 in nonABPA indicates their importance in susceptibility and resistance, respectively.

Facial angioedema in children due to ladybug (Harmonia axyridis) contact: 2 case reports.

BACKGROUND Only 9 adult cases of immediate-hypersensitivity reaction to ladybugs, also known as Asian lady beetles (Harmonia axyridis), have been documented in the literature. These patients have all shown symptoms of allergic rhinoconjunctivitis or asthma from exposure to ladybugs. OBJECTIVE To describe the first pediatric patients with severe allergic facial angioedema requiring emergency department management after exposure to ladybugs. METHODS Evidence of IgE-mediated hypersensitivity to ladybugs was documented by positive skin prick test reactions, correlating with exposure history. RESULTS Two cases in preschool boys had similar features, although they were evaluated and tested by 2 different allergists. Both patients developed severe facial or periocular angioedema with no significant respiratory involvement after exposure to ladybugs outside their infested homes. Both patients required an emergency department visit for treatment. Allergy evaluation using ladybug extract for skin prick testing showed markedly positive reactions in both patients. There were no further episodes after environmental control measures were instituted. CONCLUSIONS Although allergic respiratory or cutaneous reactions to ladybugs are uncommon, a high index of suspicion from exposure history and confirmatory skin testing can be conclusive for the diagnosis.