Is ANCA-associated vasculitis heritable? Report says it may be.
Case study of mother and son with granulomatosis with polyangiitis
A rare case of two family members with granulomatosis with polyangiitis (GPA), a type of ANCA-associated vasculitis (AAV), highlights the potential genetic underpinnings of the autoimmune disease, according to a recent report.
This case of a mother and son both presenting with GPA add to a small, but accumulating, body of evidence that AAV can be heritable.
“Information on the possible heritability of AAV is of clinical importance because family members would often want to know whether having AAV puts their closest relatives at increased risk of developing the disease,” scientists wrote.
The report, “Familial Association of Granulomatosis With Polyangiitis: A Case-Based Review of Literature,” was published in Cureus.
AAV arises from interplay between genetic and environmental factors
The mechanisms underlying AAV development remain relatively poorly understood, but it is believed that the disease arises from a complex interplay between genetic and environmental factors.
Yet, understanding the genetic contributions is difficult because, on top of AAV being a rare disease, reported cases where the condition clusters in families are very scarce.
In the recent report, scientists described a rare case of two Caucasian family members who presented with similar symptoms of GPA.
The first, a 62-year-old woman, had symptoms such as pain in the legs and feet, skin lesions, red skin, and swelling. She had also been experiencing joint pain, rash, and discoloration on her fingertips, for which a rheumatologist had previously started her on methotrexate, an immunosuppressant, for suspected inflammatory arthritis.
At the researchers’ clinic, doctors noted black discoloration and tissue death (necrosis) on her fingertips and toes, as well as an extensive lesion, or ulcer, on her shin.
She was admitted to the hospital for possible autoimmune vasculitis, and lab tests showed various signs of autoimmune disease, including a high white blood cell count and elevated rheumatoid factor, a self-reactive protein produced by the immune system.
ANCAs, the self-reactive antibodies that cause AAV, were also elevated, particularly PR3-ANCAs, the type usually associated with GPA. Markers of other autoimmune conditions were normal. Based on these and other physical findings, the woman was diagnosed with GPA.
Damaged tissue surrounding her ulcers was removed, and she was started on oral prednisone, a corticosteroid, and weekly rituximab infusions, but returned multiple times for uncontrolled pain in her lower extremities. At the time of the report, the patient remained on rituximab and was in remission.
Information on the possible heritability of AAV is of clinical importance because family members would often want to know whether having AAV puts their closest relatives at increased risk of developing the disease.
Son, 32, experienced similar symptoms
Her son, a 32-year-old man, experienced similar clinical features, with main symptoms being coughing up blood, breathlessness, rash, and joint pain. He had previously been treated with steroids for symptoms of pain and swelling in the hands without improvement.
At the hospital, the man had a fast heart rate and low blood oxygen levels, with swelling, rash, ulcers, breathlessness, and joint pain, among other symptoms.
Lab tests indicated elevated white blood cell counts and markers of inflammation, while chest X-rays indicated lung abnormalities and bleeding. He was started on prednisone.
Additional tests were negative for markers of other autoimmune diseases, and as in his mother’s case, he had very high levels of PR3-ANCAs.
Given the various physical findings and the now known family history of GPA, the man was diagnosed with an autoimmune-mediated small vessel vasculitis, which doctors believed was most likely GPA based on lab findings.
The man was started on steroids, but experienced worsening respiratory failure and quickly deteriorated. He died on his sixth day in the hospital.
To learn more about familial AAV, the scientists conducted a literature review, identifying eight studies involving 17 patients that reported familial cases. These cases all involved siblings or parents, and most — 15 of 17 patients — were diagnosed with GPA.
Family recurrence indicates ‘possible heritability in autoimmune disorders’
“Family recurrence is a strong indicator of a possible heritability in autoimmune disorders,” the researchers wrote. As such, these reports favor “a genetic pattern” for AAV.
A few large-scale genetic studies have been conducted to look for potential genetic contributors to AAV.
Such reports have found that different AAV subtypes may be linked to genetic variation in human leukocyte antigen (HLA) genes, a family of immune-related genes that’s been associated with a range of autoimmune conditions.
Thus, “genetic testing, HLA subtyping, and further studies are warranted to determine the possible hereditary transmission of the disease,” the scientists wrote.
Taken all together, findings from these studies “could help elucidate the etiology of AAV and develop new biomarkers for early diagnosis and targeted therapy,” they added.
“Although very informative, all these findings represent only the beginning of a new exciting, and dynamic phase in this field,” the team concluded.