Specific IgG subclass antibody pattern toAspergillus fumigatus in patients withcystic fibrosis with allergic bronchopulmonary aspergillosis (ABPA)

摘要

BACKGROUND—IgG and IgG subclass antibodies to Aspergillus fumigatus (A fumigatus) were measured in a large population of patients with cystic fibrosis to elucidate a putative antibody pattern specific for allergic bronchopulmonary aspergillosis (ABPA).
METHODS—An ELISA technique using water soluble somatic hyphal (WSSH) A fumigatus antigens and subclass specific monoclonal antibodies was used for cross sectional quantification of IgG and IgG1-4 subclass antibody levels in the serum of 238 patients with cystic fibrosis and 107 healthy controls.
RESULTS—In patients with cystic fibrosis persistently colonised with A fumigatus the subclass antibody levels were significantly increased compared with patients with cystic fibrosis never or rarely colonised (p<0.001). The group of patients persistently colonised with A fumigatus with ABPA (+Af+ABPA) had significantly increased levels of IgG antibodies to A fumigatus (Af-IgG) (median 69 ELISA units (EU) versus 31) and of subclasses Af-IgG1 (91 versus 27), Af-IgG2 (143 versus 56), and Af-IgG4 antibodies (72 versus 20), but not of IgG3 (17 versus 15), compared with the colonised patients without ABPA (+Af-ABPA). Patients with cystic fibrosis withno or only rare isolates of A fumigatuswithout ABPA (-Af-ABPA) also had significantly increasedsubclass antibody levels (Af-IgG1 9 versus 3, Af-IgG2 28 versus 5, Af-IgG4 16 versus 4;p<0.001) compared with healthy controls. Low, although detectable,levels of antibodies were demonstrated in healthy controls. ABPA seemedto occur independently of Pseudomonas aeruginosainfection. Using diagnostic cut off levels for ABPA, sensitivityand specificity were calculated. The highest specificity was found forIgG4 (88%); sensitivity was between 65% and 73%. Thepositive predictive values (PPV) were moderate, whereas the negativepredictive values (NPV) were high (96% in all subclasses exceptIgG3 with 94%). PPV increased to 50% if IgG1as well as IgG2 and IgG4 were included.
CONCLUSIONS—In a largenumber of unselected patients with cystic fibrosis significantlyincreased levels of Af-specific antibodies belonging to total IgG andall four subclasses were found in all groups of patients compared withhealthy controls. In patients persistently colonised withA fumigatus these levels were significantlyhigher than in non-colonised patients, and the significantly highest levels (with the exception of IgG3) were found in patientswith ABPA. Using a sensitive ELISA technique, measurements of IgG and IgG subclass antibodies to A fumigatus mightbe of importance in the management of ABPA, especially as a screeningtest to exclude the presence of ABPA; other tests are needed to confirmthe diagnosis.