scholarly journals Specific IgG subclass antibody pattern to Aspergillus fumigatus in patients with cystic fibrosis with allergic bronchopulmonary aspergillosis (ABPA)

Thorax ◽  
1999 ◽  
Vol 54 (1) ◽  
pp. 44-50 ◽  
Author(s):  
M Skov ◽  
T Pressler ◽  
H E Jensen ◽  
N Hoiby ◽  
C Koch
Author(s):  
Patience Eschenhagen ◽  
Claudia Grehn ◽  
Carsten Schwarz

BackgroundIn Cystic Fibrosis (CF), the airways are often colonized by opportunistic fungi. The most frequently detected mold is Aspergillus fumigatus (Af). Af diseases are associated with significant morbidity and mortality. The most common clinical picture caused by Af is allergic bronchopulmonary aspergillosis (ABPA), triggered by an immunological reaction against Af. Af bronchitis and invasive aspergillosis rarely occur in CF as a result of spore colonization and germination. Since pulmonary mycoses and exacerbations by other pathogens overlap in clinical, radiological, and immunological characteristics, diagnosis still remains a challenge. The search for reliable, widely available biomarkers for Af diseases is therefore still an important task today.ObjectivesAf-specific IgG m3 is broadly available. Sensitivity and specificity data are contradictory and differ depending on the study population. In our prospective study on pulmonary Af diseases in CF, we determined specific IgG m3 in order to test its suitability as a biomarker for acute Af diseases and as a follow-up parameter.MethodsIn this prospective single center study, 109 patients with CF were screened from 2016 to 2019 for Af-associated diseases. According to diagnostic criteria, they were divided into four groups (control, bronchitis, ABPA, pneumonia). The groups were compared with respect to the level of Af-specific IgG (ImmunoCAP Gm3). We performed a receiver operating characteristic (ROC) curve analysis to determine cut-off, sensitivity and specificity. Twenty-one patients could be enrolled for a follow-up examination.ResultsOf the 109 patients, 36 were classified as acute Af-disease (Af bronchitis, ABPA, Af pneumonia). Of these, 21 patients completed follow up-screening. The median Af-specific Gm3 was higher in the acute Af-disease groups. There was a significant difference in Af-specific IgG m3 compared to the control group without acute Af-disease. Overall, there was a large interindividual distribution of Gm3. A cut-off value of 78.05 mg/L for Gm3 was calculated to discriminate controls and patients with ABPA/pneumonia with a specificity of 75% and a sensitivity of 74.6%. The follow up examination of 21 patients showed a decrease of Gm3 in most patients without statistical significance due to the small number of follow up patients.ConclusionAf specific IgG may be a useful biomarker for acute ABPA and Af pneumonia, but not for Af bronchitis in CF. However, due to the large interindividual variability of Gm3, it should only be interpreted alongside other biomarkers. Therefore, due to its broad availability, it could be suitable as a biomarker for ABPA and Af pneumonia in CF, if the results can be supported by a larger multicenter cohort.


2015 ◽  
Vol 23 (3) ◽  
pp. 196-203 ◽  
Author(s):  
Coralie Barrera ◽  
Bénédicte Richaud-Thiriez ◽  
Steffi Rocchi ◽  
Bénédicte Rognon ◽  
Sandrine Roussel ◽  
...  

ABSTRACTAllergic bronchopulmonary aspergillosis (ABPA) is difficult to diagnose; diagnosis relies on clinical, radiological, pathological, and serological criteria. Our aim was to assess the performance of two new commercially available kits and a new in-house assay: anAspergillus fumigatusenzyme-linked immunosorbent assay (ELISA) IgG kit (Bordier Affinity Products), anAspergillusWestern blotting IgG kit (LDBio Diagnostics), and a new in-house time-resolved fluorometric IgE assay (dissociation-enhanced lanthanide fluorescent immunoassay, or DELFIA) using recombinant proteins from anAspergillussp. recently developed by our laboratory for ABPA diagnosis in a retrospective study that included 26 cystic fibrosis patients.Aspergillus fumigatus-specific IgG levels measured by a commercial ELISA kit were in accordance with the level of precipitins currently used in our lab. The ELISA kit could accelerate and help standardize ABPA diagnosis.Aspergillus fumigatus-specific IgE levels measured by ImmunoCAP (Phadia) withA. fumigatusM3 antigen and by DELFIA with a purified protein extract ofA. fumigatuswere significantly correlated (P< 10−6). The results with recombinant antigens glucose-6-phosphate isomerase and mannitol-1-phosphate dehydrogenase were encouraging but must be confirmed with sera from more patients. The DELFIA is an effective tool that can detect specific IgE against more fungal allergens than can be detected with other commercially available tests.


2011 ◽  
Vol 56 (2) ◽  
pp. 869-874 ◽  
Author(s):  
Pierre-Régis Burgel ◽  
Marie-Thérèse Baixench ◽  
Michaël Amsellem ◽  
Etienne Audureau ◽  
Jeanne Chapron ◽  
...  

ABSTRACTAspergillus fumigatusis the most frequent fungus found in the sputum of cystic fibrosis (CF) subjects. Itraconazole is prescribed for allergic bronchopulmonary aspergillosis (ABPA) orAspergillusbronchitis in CF subjects. We hypothesized thatA. fumigatusisolates in the sputum of CF subjects with previous exposure to itraconazole was associated with higher prevalence of azole resistance. From June 2010 to April 2011, sputum samples from adult CF subjects at Cochin University Hospital (France) were examined systematically for the detection ofA. fumigatus. MICs ofA. fumigatusisolates against azoles were screened using Etest, and reduced susceptibility to azoles was confirmed using the CLSI broth microdilution method.A. fumigatuswas isolated from the sputum of 131/249 (52.6%) adult CF subjects, and 47/131 (35.9%) subjects had received previous treatment with itraconazole. ReducedA. fumigatussusceptibility to itraconazole (MIC, ≥2 mg/liter) was confirmed in 6/131 (4.6%) subjects. All 6 isolates also had reduced susceptibility to posaconazole (MIC, ≥0.5 mg/liter), and 3/6 isolates had reduced susceptibility to voriconazole (MIC, ≥2 mg/liter). Mutations in thecyp51Agene were detected at positions previously implicated to cause resistance in 5 isolates. Azole-resistantA. fumigatusisolates were found in 5/25 (20%) subjects exposed to itraconazole within the previous 3 years. High rates of azole-resistantA. fumigatusisolates were present in adult CF subjects and were associated with recent itraconazole exposure. Although the clinical implications of these findings will require further studies, the cautious use of itraconazole in adult CF subjects can be recommended.


2006 ◽  
Vol 52 (9) ◽  
pp. 1785-1793 ◽  
Author(s):  
Erna Van Hoeyveld ◽  
Lieven Dupont ◽  
Xavier Bossuyt

Abstract Background: We evaluated the ImmunoCAP technique for measurement of IgG specific to Aspergillus fumigatus and pigeon antigens. Methods: We used ImmunoCAP and precipitation technique to measure concentrations of IgG to A. fumigatus or pigeon antigens in sera from 265 patients and 42 controls. We also evaluated linearity, interference, imprecision, concordance, and diagnostic accuracy of the measuring techniques. Results: The precipitation and ImmunoCAP technique showed moderate concordance (κ, 0.46 for both A. fumigatus and pigeon antibodies). Specific IgG results for A. fumigatus and pigeon were linear (r = 0.98 and 0.97, respectively), with interrun reproducibility rates of 23% and 14% and maximal interference of 36.5% and 8% by lipid and 24% and 21% by hemolysis, respectively. A. fumigatus antibody concentrations were higher in patients with aspergillosis and allergic bronchopulmonary aspergillosis (ABPA) (median, 103 and 70.1 mgA/L, respectively) than in patients with other pulmonary diseases (median, 18.15–33.40 mgA/L). Antibodies to pigeon antigens were high in patients with hypersensitivity pneumonitis (median, 1024 mgA/L) but also in patients with other pulmonary diseases (median, 445 mgA/L). Antibody titers were substantially higher in patients with other pulmonary diseases and contact with pigeons (median, 1060 mgA/L) than in patients without antigen contact (median, 27.35 mgA/L) (P &lt;0.004). Conclusions: Agreement between the precipitation and ImmunoCAP technique was 86% for A. fumigatus and 70% for pigeon antigens. Highest concentrations of specific IgG to A. fumigatus were found in patients with aspergillosis and ABPA. Our results suggest that antigen contact was the most important variable affecting the presence of antibodies to pigeon antigen.


2010 ◽  
Vol 17 (9) ◽  
pp. 1330-1336 ◽  
Author(s):  
Hélène Fricker-Hidalgo ◽  
Bérangère Coltey ◽  
Catherine Llerena ◽  
Jean-Charles Renversez ◽  
Renée Grillot ◽  
...  

ABSTRACT Allergic bronchopulmonary aspergillosis (ABPA) is a frequent complication in cystic fibrosis patients. The diagnosis remains difficult and requires a combination of clinical, radiological, biological, and mycological criteria. The aim of this study was to analyze the added value of two recombinant antigens, rAspf4 and rAspf6, associated with the detection of specific IgG; precipitins; total IgE; and Aspergillus fumigatus in sputum for the diagnosis of ABPA. In a retrospective study, we determined the specific IgE responses to these recombinants in 133 sera of 65 cystic fibrosis patients. We selected an average of five serum samples from each of the 17 patients with ABPA (13 proven and 4 probable ABPA) and from 3 patients with Aspergillus bronchitis and rhinosinusitis. One serum sample for the 45 patients without ABPA was tested. The sensitivity of specific IgE detection against rAspf4 calculated per patient (92.3%) was significantly higher (P < 0.05) than that of rAspf6 (53.8%). When rAspf4 IgE detection was associated with anti-Aspergillus IgG enzyme-linked immunosorbent assay (ELISA) and precipitin detection, the sensitivity rose to 100%. The specificities of rAspf4 and rAspf6 IgE detection were 93.7% and 91.6%, respectively. Other diagnostic criteria had slightly lower specificities (87.5% for anti-Aspergillus IgG ELISA, 89.6% for precipitins, 84.4% for total IgE, and 85.0% for positive A. fumigatus culture in sputum). In conclusion, this retrospective study showed the relevance of rAspf4 IgE detection, in combination with other biological markers (Aspergillus IgG ELISA, precipitins, and total IgE), for improving the biological diagnosis of ABPA.


mBio ◽  
2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Brandon S. Ross ◽  
Lotus A. Lofgren ◽  
Alix Ashare ◽  
Jason E. Stajich ◽  
Robert A. Cramer

Aspergillus fumigatus infection causes a spectrum of clinical manifestations. For individuals with cystic fibrosis (CF), allergic bronchopulmonary aspergillosis (ABPA) is an established complication, but there is a growing appreciation for A. fumigatus airway persistence in CF disease progression.


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