Fumigatus-specific Antibody Research Articles

Aspergillosis infection over 20\u2009years: a case report of probable vascular invasion in central nervous system

BackgroundAspergillosis infection of central nervous system (CNS) is rare and fatal. Diagnosis of invasive aspergillosis remains difficult. Aspergillosis of CNS can be an acute, subacute, or chronic onset, and the longest course of the disease was currently reported to be 4 years. Here, we report a case with recurrent headache over 20 years.Case presentationA 54-year-old man was admitted to our neurological disease ward due to intermittent throbbing headache lasting for more than 20 years that had grown notably worse over the past week. The headache was localized to the side of his head blown by a cold wind. He also experienced nausea and vomiting when the headache became severe. The headache usually lasted for 3–4 h after he was blown by the cold wind, though he had no fever. The neurological examination was normal. Magnetic resonance imaging (MRI) of the brain was negative for parenchymal and meningeal lesions. However, the case had increased intracranial pressure (ICP), and elevated protein level in the cerebrospinal fluid (CSF). Aspergillus fumigatus was found in CSF by nanopore targeted sequencing (NTS) and in blood by enzyme-linked immunosorbent assay (ELISA). Aspergillus fumigatus-specific antibody IgG was 104.62 AU/mL, aspergillus galactomannan (GM) antigen was 3.27 μg/L, D-dimer was 3.25 mg/L and fibrinogen degradation product was 11.50 mg/L, which were markedly higher than the normal levels. The patient was prescribed by voriconazole. After the treatment of 14 days, the ICP, CSF protein level, Aspergillus fumigatus-specific antibody IgG, GM antigen, D-dimer and fibrinogen degradation product returned normal. Aspergillus was disappeared by NTS test of CSF. His headache has never occurred again after blowing by a cold wind.ConclusionsThis report reveals that aspergillosis infection of CNS can last for more than 20 years and the major symptom is only intermittent throbbing headache in an immunocompetent patient. Vascular invasion is probably the mechanism of headache in our case with CNS aspergillosis infection. Performing high-throughput gene sequencing technology in CSF is important when the pathogen is not determined for the patients with suspected CNS infection.

Management of allergic aspergillosis

Treatment of allergic bronchopulmonary aspergillosis depends on accurate diagnosis, which is difficult because of multiple clinical, radiographic, and immunologic criteria; unstandardized immunoassays; and its similarity to cystic fibrosis. Advances in chest CT interpretation, measuring serum Aspergillus fumigatus-specific antibodies and the T-helper type 2 chemokine thymus-activated-and-regulated chemokine, recognizing risk factors, should improve diagnostic accuracy. Oral glucocorticosteroids remain the mainstay of treatment. Dose regimen and duration are not standardized, so expert recommendations are used. Inhaled steroids have not been proven to be effective. Due to relapse and toxicity, itraconazole has been added as second-tier therapy, supported by randomized, placebo-controlled trials in asthma and open-label trials in cystic fibrosis. Itraconazole is steroid sparing with anti-inflammatory aspects and poor bioavailability. Despite combination steroid-itraconazole therapy, relapses and steroid toxicity have led to open-label use of voriconazole, nebulized amphotericin B, monthly high-dose intravenous methylprednisolone, and omalizumab. Controlled trials are needed to evaluate these and other antifungal or immunomodulatory interventions.

Management of allergic aspergillosis

Treatment of allergic bronchopulmonary aspergillosis depends on accurate diagnosis, which is difficult because of multiple clinical, radiographic, and immunologic criteria; unstandardized immunoassays; and its similarity to cystic fibrosis. Advances in chest CT interpretation, measuring serum Aspergillus fumigatus-specific antibodies and the TH2 chemokine thymusactivated-and-regulated chemokine, recognizing risk factors, should improve diagnostic accuracy. Oral glucocorticosteroids remain the mainstay of treatment. Dose regimen and duration are not standardized, so expert recommendations are used. Inhaled steroids have not been proven to be effective. Due to relapse and toxicity, itraconazole has been added as second-tier therapy, supported by randomized, placebo-controlled trials in asthma and open-label trials in cystic fibrosis. Itraconazole is steroid sparing with anti-inflammatory aspects and poor bioavailability. Despite combination steroid-itraconazole therapy, relapses and steroid toxicity have led to open-label use of voriconazole, nebulized amphotericin B, monthly high-dose intravenous methylprednisolone, and omalizumab. Controlled trials are needed to evaluate these and other antifungal or immunomodulatory interventions.

Distinct CD4+-T-Cell Responses to Live and Heat-InactivatedAspergillus fumigatusConidia

Aspergillus fumigatus is an important fungal pathogen that causes invasive pulmonary disease in immunocompromised hosts. Respiratory exposure to A. fumigatus spores also causes allergic bronchopulmonary aspergillosis, a Th2 CD4+-T-cell-mediated disease that accompanies asthma. The microbial factors that influence the differentiation of A. fumigatus-specific CD4+ T lymphocytes into Th1 versus Th2 cells remain incompletely defined. We therefore examined CD4+-T-cell responses of immunologically intact mice to intratracheal challenge with live or heat-inactivated A. fumigatus spores. Live but not heat-inactivated fungal spores resulted in recruitment of gamma interferon (IFN-gamma)-producing, fungus-specific CD4+ T cells to lung airways, achieving A. fumigatus-specific frequencies exceeding 5% of total CD4+ T cells. While heat-inactivated spores did not induce detectable levels of IFN-gamma-producing, A. fumigatus-specific CD4+ T cells in the airways, they did prime CD4+ T-cell responses in draining lymph nodes that produced greater amounts of interleukin 4 (IL-4) and IL-13 than T cells responding to live conidia. While immunization with live fungal spores induced antibody responses, we found a marked decrease in isotype-switched, A. fumigatus-specific antibodies in sera of mice following immunization with heat-inactivated spores. Our studies demonstrate that robust Th1 T-cell and humoral responses are restricted to challenge with fungal spores that have the potential to germinate and cause invasive infection. How the adaptive immune system distinguishes between metabolically active and inactive fungal spores remains an important question.

Analysis of HIV seropositive thalassemic children for antibodies specific to Aspergillus fumigatus by luminescent immunoassay.

The applicability of luminescent immunoassay (LIA) in serodiagnosis of fungal infections in multitransfused (MT) thalassemic children seropositive for human immunodeficiency virus (HIV) was investigated. Thirty-one sera samples from HIV infected pediatric patients with thalassemia receiving repeated blood transfusions were analysed for the presence of antibodies specific to Aspergillus fumigatus by LIA. The LIA was standardized using well defined antigens of A. fumigatus. Ten out of 31 (32.2%) of the MT-HIV positive patients were found to have anti-Aspergillus antibodies in their sera by LIA. The ELISA could detect A. fumigatus specific antibodies in 25.8% (8 out of 31) of the patients. Thus, 20% more number of patients turned to be positive for aspergillosis by LIA as compared to ELISA. The difference was found to be statistically significant (p < 0.005). Of the MT-HIV negative patients only 1 out of 33 (3%) showed A. fumigatus specific antibodies by LIA and ELISA both. In age and sex matched control group (n = 25) none of the patients was found to be positive for antibodies to A. fumigatus. LIA was found to have better discriminatory value indicating, thereby, its utility in diagnosis of aspergillosis in compromised patients.

Dexamethasone and cyclosporin A modulation of cytokine expression and specific antibody synthesis in an allergic bronchopulmonary aspergillosis murine model.

We previously demonstrated that, in C57B1/6 mice, cyclosporin A enhanced and dexamethasone inhibited the Aspergillus fumigatus-induced pulmonary eosinophilia and total IgE levels. To evaluate whether these effects were related to the modulation of T-lymphocyte recruitment and activation and cytokine expression, we performed immunohistochemical staining for T-cell surface marker CD3 and CD4, cell activation marker CD25, and cytokines granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-4 (IL-4) and interleukin-5 (IL-5) on lung tissue sections from mice exposed to Aspergillus fumigatus and treated or not with dexamethasone or cyclosporin A. Dexamethasone significantly inhibited Aspergillus fumigatus-induced increased number of activated T cells and cytokine-expressing cells in parallel with a decrease in pulmonary eosinophils. In contrast, cyclosporin A did not decrease these immunological events but enhanced the lung eosinophil recruitment. Moreover, dexamethasone prevented the production of immunoglobulins against 76 and 36 kD antigen proteins and cyclosporin A against 76 and 18 kD antigen proteins. These results indicate that dexamethasone down-regulates and cyclosporin A up-regulates lung eosinophil recruitment and total IgE production, probably via the modulation of T-lymphocyte activation and GM-CSF, IL-4 and IL-5 expression. Both drugs inhibit Aspergillus fumigatus-specific antibody synthesis, but their suppressive actions are selective to different antigenic components.

Aspergillus fumigatus-specific antibodies in allergic bronchopulmonary aspergillosis and aspergilloma: evidence for a polyclonal antibody response

Patients with the Aspergillus-induced diseases allergic bronchopulmonary aspergillosis (ABPA), aspergilloma (fungus ball), and Aspergillus skin test-positive asthma were differentiated immunologically by radioimmunoassay based on their total immunoglobulin E (IgE) and Aspergillus fumigatus-specific IgE levels. In this study, a new, highly sensitive biotin-avidin-linked immunosorbent assay was used to evaluate A. fumigatus-specific antibodies of all immunoglobulin classes. Studied populations included 13 patients with ABPA, 12 with aspergilloma, 9 with Aspergillus skin test-positive asthma, and 9 normal individuals without asthma. A. fumigatus-specific antibodies of all classes were elevated in patients with ABPA, variably elevated in those with aspergilloma, and lowest in the other two groups. This assay demonstrated significantly higher specific IgE antibody levels in the ABPA group over those of the other groups, even with 1:1,000 dilutions of the sera. This study demonstrated that ABPA is a disease characterized by a polyclonal antibody response to Aspergillus antigen and not just a response to IgE and IgG antibody classes. The measurement of other antibody classes, particularly IgD and IgA, could enhance the immunodiagnosis of ABPA. The biotin-avidin-linked immunosorbent assay was found to be a highly sensitive assay that can be a clinically useful alternative to radioimmunoassay in the measurement of A. fumigatus-specific antibodies.

Enzyme-linked immunosorbent assay in the detection of specific antibodies against Aspergillus in patient Sera

A biotin-avidin linked enzyme immunoassay (BALISA) was used to detect Aspergillus fumigatus specific antibodies in the sera of patients with aspergillosis. Culture filtrate antigens from a strain of A. fumigatus grown in synthetic medium was used in the ELISA. This antigen was characterized by various immunochemical methods including isoelectric focusing, two-dimensional electrophoresis and antigen antibody crossed-immunoelectrophoresis. Sera from patients having allergic asthma, allergic bronchopulmonary aspergillosis (ABPA), aspergilloma and normal controls were studied. High levels of IgE and IgG antibodies specific to A. fumigatus antigens were detected in ABPA while only IgG antibodies were seen in aspergilloma. The normal group and the allergic asthma failed to show any differences in the specific antibody content. Biotin-avidin linked immunosorbent assay was found to be very useful in detecting both IgG and IgE antibodies, and by using characterized antigens reproducible and dependable results can be obtained.