Expanded ANCA Testing May Improve AAV Diagnosis, Classification, Study Says

Expanded ANCA Testing May Improve AAV Diagnosis, Classification, Study Says

A new test that recognizes anti-neutrophil cytoplasmic autoantibodies (ANCAs) targeting proteins other than myeloperoxidase (MPO) and proteinase-3 (PR-3) could improve the diagnosis and classification of ANCA-associated vasculitis, a study suggests.

The study, “ANCA Beyond MPO & PR-3: the Clinical Utility of an Expanded ANCA Profile,” was recently presented at the 19th International Vasculitis and ANCA Workshop in Philadelphia.

ANCA-associated vasculitis is a group of autoimmune diseases characterized by the presence of ANCAs — autoantibodies against proteins present in neutrophils.

These autoantibodies wrongly activate neutrophils attached to the blood vessel wall, triggering their defense mechanisms, which ultimately damage the walls of small vessels in different tissues and organs.

There are three major types of ANCA vasculitis, each with different symptoms and prognosis, and one way of differentiating them is by determining the type of ANCAs they produce.

Most ANCAs attack either the MPO or PR-3 proteins at the surface of neutrophils, but in some cases, patients have antibodies targeting different neutrophil proteins other than these molecules; in these cases, they have what is called “atypical ANCA.”

ANCAs are currently classified using a combination of two tests. The first, called immunofluorescence, determines the presence and location of ANCAs in samples of neutrophils observed under a microscope. The second, called enzymatic immunoassay (EIA), identifies whether those autoantibodies specifically target PR-3 or MPO.

Because these approaches fail to identify other targets of ANCAs — which could improve the diagnosis and classification of ANCA vasculitis subtypes — researchers at the Lexington Medical Center in South Carolina developed a new six-test assay called the Expanded ANCA Specificity EIA Profile aimed at reducing the number of cases classified as atypical ANCA.

The assay determines if autoantibodies in neutrophils target not only PR-3 or MPO, but also four other proteins — lactoferrin, elastase, BPI, and cathepsin-G — or a combination of any of these.

The investigators tested 1,850 possible ANCA-associated vasculitis samples. A total of 1,578 (85%) were negative for autoantibodies, and 272 (15%) were positive by immunofluorescence, 112 of which (41%) targeted either PR3 or MPO.

The new test was used to analyze the 81 samples defined as atypical ANCA, and successfully classified 79 of them. ANCAs in those samples targeted either one of the four remaining proteins (58 samples) or a combination of proteins (21 samples).

Of particular note is that 18 of the samples targeting a protein combination included at least one protein not previously reported in ANCA-associated vasculitis.

These results underscore the complexity of this disorder and suggest that “routine use of an expanded profile for ANCA antigen specificities will further expand the diagnostic utility of ANCA testing — similar to follow-up testing,” the researchers said.

Alejandra has a PhD in Genetics from São Paulo State University (UNESP) and is currently working as a scientific writer, editor, and translator. As a writer for BioNews, she is fulfilling her passion for making scientific data easily available and understandable to the general public. Aside from her work with BioNews, she also works as a language editor for non-English speaking authors and is an author of science books for kids.
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Alejandra has a PhD in Genetics from São Paulo State University (UNESP) and is currently working as a scientific writer, editor, and translator. As a writer for BioNews, she is fulfilling her passion for making scientific data easily available and understandable to the general public. Aside from her work with BioNews, she also works as a language editor for non-English speaking authors and is an author of science books for kids.
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