Clin. GM protein derived from was not evident. Therefore, the chemical nature of the epitopes captured in this assay is most likely not associated with the GM structure, indicating that this newly developed antigen-capture ELISA is a promising tool for the diagnosis LY450108 of IA without the risk of the false-positive results that are problematic with current GM antigen assays. In recent years, the numbers of cases of invasive aspergillosis (IA) associated with high rates of morbidity and mortality have increased, likely due to the greater prevalence of immunosuppressive therapies LY450108 being performed (6, 33). IA is most commonly caused by and and less frequently by (6). The early and accurate diagnosis of IA is critical in improving the prognosis for patients through the delivery of more prompt antifungal therapy and lessening the unnecessary use of toxic antifungal drugs (32). However, the early clinical diagnosis of IA is often difficult, since the signs and symptoms of infection are nonspecific. A positive blood fungal culture is rarely obtained during the early stage of the infection, and antibody detection is often negative, as the majority of immunosuppressed patients have a weak antibody response (13, 38). Recent efforts to improve the early diagnosis of IA have focused on the detection of circulating antigens. Galactomannan (GM), which is present in the cell walls of most species, is an effective marker for facilitating the early detection of the antigenemia of IA (28). Polyclonal antibodies are capable of detecting the GM of (2, 4, 8). However, assays based on such antibodies are subject to variable intra- and interlaboratory results due to batch-to-batch variations in antisera. In addition, antigen tests based on polyclonal antibodies raised against crude fungal antigens exhibit significant cross-reactivity with several fungal antigens (7). Monoclonal LY450108 antibody (MAb)-based immunodiagnostic assays are preferred over polyclonal antibody-based assays. PTGS2 Two immunoassays that employ a rat immunoglobulin M (IgM) MAb designated EB-A2 for the detection of circulating GM have recently been developed (24, 25). One of these, designated the Platelia assay (Bio-Rad, Marnes-La-Coquette, France), is a commercially available, double-sandwich enzyme-linked immunosorbent assay (ELISA) that utilizes MAb EB-A2 as both the capture and the detector antibody; the assay enjoys worldwide use for the diagnosis of IA (17). Studies that have evaluated the Platelia assay have documented a high percentage of false-positive results when serum or urine samples from immunocompromised patients without evidence of aspergillosis are tested (29, 30), even though antigen detection is sensitive. Other studies have reported a high incidence of false-positive results (up to 74%) when the assay system is used to test patients treated with GM, but also recognizes cross-reacting epitopes on other fungal polysaccharide cell wall components (i.e., species) (13, 25). Thus, the occurrence of false-positive results may be caused by the cross-reactive epitopes in human serum or contamination by other fungal components. Since many antibiotics originate from fungi (i.e., ampicillin-sulbactam, piperacillin-tazobactam, and amoxicillin-clavulanic acid) and since these drugs are commonly used for the management of febrile immunosuppressed patients, the occurrence of false-positive results in patients during the administration of these drugs may limit the utility of the Platelia assay, leading to inappropriate treatment. This concern may also extend to pediatric populations (21), with which false-positive rates are as high as 83% (23). The false-positive results most likely relate to the cross-reacting epitopes of MAb EB-A2 with lipoteichoic acid, which is abundant in the neonatal gut and which may be transported through the immature intestinal mucosa into the bloodstream (18). LY450108 Indeed, cross-reactions of rat anti-GM MAb EB-A2 have been described with other organisms and foods (1, 13, 17, 22, 34). It is conceivable that the passage of food-derived GM through intestinal mucosa damaged as a result of chemotherapy may underlie the cross-reactivity (12). With the aim of improving the diagnosis of IA, we produced.