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[Analysis of Cases with Elevated Blood (1->3)-β-D-glucan in Relation to an Infection Marker, Neutrophil CD64
Abstract:
(1->3)-β-D-glucan (BDG) is a constituent of the fungal cell wall and its blood level is known as a marker of fungal infection including pneumocystis pneumonia (PCP). Meanwhile, peripheral blood neutrophil CD64 expression (CD64) is upregulated in various infections. We analyzed patients with positive BDG (cut off 11.0 pg/mL) and those whose CD64 was measured simultaneously. In patients who visited our hospital from 2005 to 2011, BDG was measured in 3,960 samples. The number of positive samples were 441 obtained from 185 patients. In patients with positive BDG, the initial BDG was 24.3 [16.4-70.5] pg/mL (median [interquartile range]). Positive BDG samples were derived mainly from the department of Rheumatology or that of Allergy and Respirology. Common primary diseases were rheumatoid arthritis (RA) or other connective tissue diseases, followed by malignancy, none (only abnormal chest X-ray) and bronchial asthma. The rates of afebrile patients, patients on immunosuppressive therapy and those with a normal range of white blood cell count were 63.7%, 50.9% and 40.8%, respectively. The main causes of positive BDG were PCP (n = 38, 20.5%) and non-PCP mycosis (n = 48, 25.9%, including 26 cases of aspergillosis). Others (99 patients, 53.6%) had positive BDG of unknown origin and 53 of them ameliorated spontaneously, most of whom could have been examples of pseudo-positive BDG. The number of deceased patients was 57 (30.8%) consisting of 9 PCP, 16 non-PCP mycosis and others. The median initial positive BDG levels in patients with PCP, non-PCP mycosis and others were 49.9, 28.9 and 19.7pg/mL, respectively. The positive rate of CD64 (cut off 2,000 molecules/cell) measured simultaneously with initial positive BDG was 77.8%. In RA patients with PCP, 94.7% of them had positive CD64 and the levels of CD64 were significantly higher than those in RA patients with bacterial pneumonia (median 9,386 vs 4,399 molecules/cell) in that same period. The positive rate of CD64 was lower in patients with positive BDG of unknown origin than those with PCP or non-PCP mycosis, which implies positive CD64 can exclude pseudo-positive BDG. Immunosuppressed patients often exhibit positive BDG. Simultaneous measurement of BDG and CD64, a quick pan-infection marker, assists the decision whether the positive BDG is true or false-positive.
Insights
This study shows that combining (1->3)-β-D-glucan (BDG) and CD64 expression tests helps distinguish true fungal infections from false positives, especially in immunosuppressed patients. This aids in accurate diagnosis and treatment decisions for fungal infections.
Area of Science:
- Medical diagnostics
- Clinical microbiology
- Immunology
Context:
- Fungal infections, including Pneumocystis pneumonia (PCP), are significant health concerns.
- (1->3)-β-D-glucan (BDG) is a biomarker for fungal infections, while CD64 expression on neutrophils indicates various infections.
- Distinguishing true fungal infections from non-infectious causes of elevated BDG is clinically important, particularly in immunocompromised patients.
Purpose:
- To evaluate the utility of simultaneous measurement of (1->3)-β-D-glucan (BDG) and peripheral blood neutrophil CD64 expression (CD64) in diagnosing fungal infections.
- To assess the correlation between positive BDG levels and specific primary diseases, treatment statuses, and patient outcomes.
- To determine if CD64 expression can help differentiate true fungal infections from pseudo-positive BDG results.
Summary:
- A retrospective analysis of 3,960 samples revealed 441 positive BDG results, primarily from patients with rheumatoid arthritis or other connective tissue diseases, malignancy, or asthma.
- Pneumocystis pneumonia (PCP) and non-PCP mycoses were the main causes of positive BDG, accounting for 20.5% and 25.9% respectively. A significant proportion of positive BDG cases were of unknown origin, with some potentially being pseudo-positive.
- Simultaneous CD64 measurement showed a high positive rate (77.8%) and was significantly elevated in RA patients with PCP compared to bacterial pneumonia, suggesting CD64 can help exclude pseudo-positive BDG results.
Impact:
- Simultaneous BDG and CD64 testing offers a valuable tool for clinicians to accurately diagnose fungal infections and guide treatment strategies.
- The findings highlight the importance of considering patient context, such as immunosuppressive therapy, when interpreting BDG results.
- This diagnostic approach can improve patient management by reducing misdiagnosis and ensuring timely intervention for true fungal infections.
