Aspergillus Precipitating Antibodies, IgG

Serum

0.3 mL

0.2 mL (Note: This volume does not allow for repeat testing.)

Gel tube

Detection of Aspergillus IgG Precipitins

Although ABPA and CPA represent two distinct manifestations of Aspergillus-related lung disease, a patient can evolve with time from one category to the other, making the specific diagnosis challenging, particularly in the context of chronic lung disease.^{14,16,18,25,36} It should also be noted that in some patients with CPA, the Aspergillus IgG may remain negative even in the presence of symptoms, radiology, and laboratory diagnostics.^25,28 Lastly, while the LabCorp Aspergillosis precipitins assay includes most species associated with Aspergillus-related lung disease, several other species not tested for have been implicated in aspergillosis in certain populations.

Ouchterlony gel double-diffusion

Aspergillus species are ubiquitous environmental molds that grow on organic matter and aerosolize conidia.^1,3 Humans inhale hundreds of conidia per day without adverse consequences, except for a small minority of people for whom infection with Aspergillus causes significant morbidity. The clinical manifestations of aspergillosis are determined by the host immune response to exposure with the spectrum ranging from a simple allergic response to local lung disease with mycelial balls to catastrophic systemic Aspergillus infection.

Aspergillus is a genus of molds that includes several hundred species that grow in nutrient-depleted environments.^1,3 These obligate aerobes are ubiquitous and can be found in virtually every oxygen-rich setting. Aspergillus molds are saprophytes that thrive on decaying organic matter. They are often found as contaminants of starchy foods and other carbon-rich substrates. They are commonly found in soil and marine habitats as well as indoor environments and in drinking water.² Of the hundred species identified, only a few have been associate with pathology in humans.^2-4 Aspergillus fumigatus is the species most commonly associated with disease.⁵ Other species that have been linked to disease include A. flavus, A. glaucus, A. niger, A. nidulans and A. terreus.^5-14

Aspergillus molds continuously disseminate spores (conidia) into the environment.² Humans are constantly exposed to airborne Aspergillus spores which, once inhaled, can access the most distal airways of the lungs due to their size and durability.¹⁴ In immunocompetent individuals with healthy lungs, inhaled conidia are eliminated by the neutrophils and macrophages of the innate immune system and do not lead to disease.^2,14 Illness only develops in a small proportion of patients with altered immune systems or underlying lung pathology.^1,3,14-17 Non-invasive forms of Aspergillus-induced lung disease include Allergic Bronchopulmonary Aspergillosis (ABPA) and Chronic Pulmonary Aspergillosis (CPA).^4,18 In severely immunocompromised individuals, Aspergillus infection of the respiratory system can spread to other organs in a condition referred to as Invasive Pulmonary Aspergillosis (IPA).^2,3,15 Antibody testing is central to diagnosis of these conditions, with raised Aspergillus-specific IgG often seen in patients with ABPA and CPA. Antibody levels are also used to monitor treatment response in these syndromes.

Allergic Bronchopulmonary Aspergillosis (ABPA)

ABPA is a relatively uncommon allergic reaction to Aspergilli that almost exclusively affects individuals with asthma or cystic fibrosis.^4,14,15,19 ABPA typically causes bronchospasm and mucus buildup resulting in coughing, breathing difficulty and airway obstruction. Bronchiectasis can develop resulting in worsening lung function and increased risk of infection. ABPA in patients with poorly controlled asthma has also been referred to as Severe Asthma with Fungal Sensitization (SAFS).²⁰

The diagnostic criteria for ABPA include the presence of a predisposing condition (asthma or cystic fibrosis) and positive allergen specific IgE to aspergillus species and a total IgE >1000 IU/mL.^21,37-39 Serum aspergillus IgG precipitins and a blood eosinophil count >500 cells/L in corticosteroid naive patients support the diagnosis of ABPA.²¹ A positive precipitin reaction against A. fumigatus can be demonstrated in 69-90% of patients with ABPA.^37,38 but also in 10% of asthmatics without ABPA³⁹ and in semi-invasive forms of aspergillosis like CPA.

Chronic Pulmonary Aspergillosis (CPA)

CPA is an uncommon, slowly destructive pulmonary disease characterized by progressive lung cavitation, fibrosis, and pleural thickening caused by Aspergillus infection of the pulmonary parenchyma in subjects with normal or mildly suppressed immunity and underlying structural lung disease.^{6,14-17, 22-27} Predisposing conditions include pulmonary tuberculosis, nontuberculous mycobacterial infection, sarcoidosis, pneumothorax, chronic obstructive pulmonary disease, surgically treated lung cancer and other cavitating or bullous lung conditions. Patients with CPA can present with chronic productive cough, weight loss and hemoptysis with nodules, cavities or fungal balls (aspergilloma) on chest imaging.

The most common form of CPA is chronic cavitary pulmonary aspergillosis (CCPA), defined as one or more pulmonary cavities that may or may not contain solid or liquid material or a fungal ball with significant pulmonary or systemic symptoms and overt radiographic progression.^2,23 Untreated, CCPA can progress to chronic fibrosing pulmonary aspergillosis (CFPA).²⁵ A less common manifestation of CPA is the simple aspergilloma, a fungal ball consisting of Aspergillus hyphae, fibrin and other debris, formed within a pre-existing area of pulmonary scar or cavity that has been colonized by Aspergillus.^15,22,25

Guidelines for the diagnosis and management of CPA were published in 2016 jointly by the European Society for Clinical Microbiology and Infectious Diseases (ESCMID), the European Respiratory Society (ERS), and the European Confederation of Medical Mycology (ECMM).²⁵ Also, the Infectious Diseases Society of America (IDSA) established recommendations for the diagnosis of CPA in the same year.²³ According to these guidelines, the diagnosis of CPA requires one or more cavities with or without a fungal ball or nodules present on thoracic imaging for ≥ 3 months, direct evidence of Aspergillus infection (microscopy or culture from biopsy) or an immunological response to Aspergillus specie(s), and exclusion of alternative diagnoses.²⁵ Several studies support the utility of measuring Aspergillus precipitins for diagnosing CPA.^5,24,28-30 A recent study indicated that the test was positive in more than 95% of cases³² while another study indicated 89.3% positivity compared to only 50% with Aspergillus galactomannan antigen ELISA tests.³¹ The Aspergillus IgG precipitins test has been reported to have a positive predictive value of 100% in differentiating infected and colonized individuals.^25,33 If antibody testing is not positive, then other evidence of Aspergillus infection is required.²⁵

Invasive Pulmonary Aspergillosis (IPA)

Chronic and allergic forms of aspergillosis are much more common than IPA.^34,35 Aspergillus infection in severely immunocompromised patients, such as individuals with hematological cancers or organ/stem cell transplant recipients, can lead to IPA, the most serious entity on the spectrum of pulmonary aspergillosis.^17,23 This life threatening disease is characterized by invasion of lung tissue by Aspergillus hyphae and subsequent spread into the lung parenchyma and associated vasculature.¹⁴ IPA can lead to intravascular thrombosis and hemorrhagic pulmonary infarction¹⁵ and has a relatively rapid progression (ranging from days to a few weeks) with a very high mortality rate.^14,17,23,30 Aspergillus IgG precipitins testing is generally not useful in the diagnosis of IPA due to the lack of antibody production in severely immunocompromised patients.^15,23,28