Researchers have presented evidence suggesting that antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) may be heritable, according to a study published in Cureus. If confirmed, this will have widespread clinical and therapeutic implications.
“Despite extensive research, the mechanism behind AAV etiology remains obscure,” the authors of the study wrote.
Because of the rarity of familial cases of an already rare disease, there is yet to be a concerted effort to explore the possibility that AAV might be heritable.
Nevertheless, multicenter genome-wide association studies (GWAS) have greatly contributed to the understanding of the genetics underlying the disease. One of the findings from these studies is that AAV subtypes are associated with distinct human leukocyte antigen (HLA) variants.
Read more about AAV etiology
This is a point of interest because family members who have been diagnosed with the same disease, such as rheumatoid arthritis or systemic lupus erythematosus, have been shown to share an identical HLA haplotype; there are reports of this happening among family members with granulomatosis with polyangiitis (GPA) as well.
Two case reports were presented, highlighting the potential hereditary nature of AAV. The first was of a mother, the second was of her son. The first case details a 62-year-old woman who initially presented with bilateral lower extremity pain, as well as ulceration, erythema, and swelling on her lower extremities.
Laboratory investigations revealed leukocytosis and anemia. Serology indicated raised titers of antinuclear antibodies of 160 with indirect immunofluorescence showing a speckled pattern, cytoplasmic ANCA of 320, and anti-proteinase-3 of 51.5. Her erythrocyte sedimentation rate was elevated at 60 mm/hr.
Skin punch biopsy demonstrated palisaded neutrophilic granulomatous dermatosis, commonly seen in primary systemic vasculitis. In addition, her right lower lobe bronchoalveolar lavage demonstrated findings consistent with diffuse alveolar hemorrhage. The patient was hence diagnosed with GPA.
Notably, the patient’s 32-year-old son was separately admitted and was diagnosed with an autoimmune-mediated small vessel vasculitis, judged highly likely to be GPA.
“Recently, there have been a few more reports of familial AAV favoring a genetic pattern,” the authors of the study wrote. “Genetic testing, HLA subtyping, and further studies are warranted to determine the possible hereditary transmission of the disease.”
Farrukh L, Mumtaz A, Sami F, et al. Familial association of granulomatosis with polyangiitis: a case-based review of literature. Cureus. 2023;15(6):e40786. doi:10.7759/cureus.40786