Muscle Biopsies Could Be Useful in AAV Diagnosis, Study Asserts

Muscle Biopsies Could Be Useful in AAV Diagnosis, Study Asserts
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Muscle biopsies could be used to diagnose ANCA-associated vasculitis (AAV), a new study indicates. The finding suggests that such biopsies are most informative in females or in people with certain inflammation-related conditions.

The study, “Muscle biopsy in anti-neutrophil cytoplasmic antibody–associated vasculitis: diagnostic yield depends on anti-neutrophil cytoplasmic antibody type, sex and neutrophil count,” was published in Rheumatology.

AAV is characterized by vasculitis — inflammation of the blood vessels. This is often accompanied by the presence of self-targeting antibodies (the ANCAs from which the disease gets its name), most commonly those that target myeloperoxidase (MPO) or proteinase 3 (PR3).

Although testing for ANCAs can help, diagnosing AAV is often difficult, often  requiring both the exclusion of other possible causes of symptoms and finding evidence for the disease in tissue biopsies.

Biopsies of the kidney can provide useful data, but aren’t always feasible.  Generally, these biopsies are done only when other lab tests (e.g., analyses of urine) already indicate kidney damage, and they may be too risky to perform in people with high blood pressure or other conditions.

Some studies have suggested that muscle biopsy could be useful for detecting vasculitis and, by extension, diagnosing AAV. However, owing largely to small sample sizes, these previous studies haven’t been able to make reliable conclusions about what patient factors make muscle biopsy more or less likely to provide useful diagnostic information.

In the new study, researchers the Nantes University Hospital, in France, reviewed medical records from AAV patients followed at their center from 1995 to 2018.

In total, they identified 78 people, including 33 with granulomatosis with polyangiitis (GPA), 25 with microscopic polyangiitis (MPA), and 20 with eosinophilic granulomatosis with polyangiitis (EGPA). Their median age was 67 years, and all of the patients had active disease at the time of the biopsy.

Most of the 78 biopsies were collected from the muscle in the thigh. The biopsies were assessed under a microscope by a pathologist, who scored them as positive or negative for the presence of vasculitis.

Overall, 45 of the muscle biopsies were positive, resulting in a sensitivity (true-positive rate) of 58%. This sensitivity was similar across the different subtypes of AAV.

The researchers constructed statistical models, taking into account multiple relevant variables, to identify factors that were associated with a greater likelihood of a positive muscle biopsy. Since all of the patients included had confirmed AAV with active disease at the time of biopsy, the identified factors are indicative of when muscle biopsy would be more likely to provide useful diagnostic information, as opposed to false-negative results.

Among individuals with MPO or GPA, three factors were significantly associated with a higher likelihood of muscle biopsy positivity: female sex, having ANCAs against MPO, and elevated neutrophil count. Among those with EGPA, the only significant predictor of muscle biopsy positivity was female sex.

That anti-MPO ANCAs and neutrophil counts were associated with muscle biopsy positivity was, according to the researchers, largely expected, and makes sense based on what is known about AAV and its subtypes: “the higher frequency of muscle vasculitis in anti-MPO ANCA patients is consistent with their frequent purely vasculitic presentation, whereas anti-PR3 ANCA patients may suffer predominantly respiratory GPA manifestations,” they wrote.

“Neutrophils are key drivers of vascular lesions in AAV,” the researchers added. “Thus one may speculate that a high neutrophil count leads to more widespread vasculitis and consequently higher MB [muscle biopsy] yield.”

In contrast, the identification of female sex as a relevant factor was described as “unexpected.” It’s not clear why such an association would exist because, “unlike other immune-mediated diseases, little if any data are available regarding the impact of sex on the [manifestations] of AAV,” the researchers wrote. As such, there is a need for further research in this field.

The researchers noted that their study, “suffers the typical limitations of retrospective studies,” such as incompletely recorded data and substantial variation in the care provided, both at different time and from different carers. Additionally, they noted that, from the available data, they couldn’t make firm conclusions about how muscle biopsy utility would change based on treatment, highlighting another avenue for further research.

“In conclusion, MB is a safe and efficient tool to obtain pathological proof of vasculitis in AAV. We demonstrated that its diagnostic yield depends on sex, ANCA type and neutrophil count,” the researchers wrote. “We suggest the quadriceps femoris MB should be considered in non-renal AAV or in the event of kidney biopsy contraindication.”

Marisa holds an MS in Cellular and Molecular Pathology from the University of Pittsburgh, where she studied novel genetic drivers of ovarian cancer. She specializes in cancer biology, immunology, and genetics. Marisa began working with BioNews in 2018, and has written about science and health for SelfHacked and the Genetics Society of America. She also writes/composes musicals and coaches the University of Pittsburgh fencing club.
Total Posts: 16
Inês holds a PhD in Biomedical Sciences from the University of Lisbon, Portugal, where she specialized in blood vessel biology, blood stem cells, and cancer. Before that, she studied Cell and Molecular Biology at Universidade Nova de Lisboa and worked as a research fellow at Faculdade de Ciências e Tecnologias and Instituto Gulbenkian de Ciência. Inês currently works as a Managing Science Editor, striving to deliver the latest scientific advances to patient communities in a clear and accurate manner.
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Marisa holds an MS in Cellular and Molecular Pathology from the University of Pittsburgh, where she studied novel genetic drivers of ovarian cancer. She specializes in cancer biology, immunology, and genetics. Marisa began working with BioNews in 2018, and has written about science and health for SelfHacked and the Genetics Society of America. She also writes/composes musicals and coaches the University of Pittsburgh fencing club.
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