AUTHOR=Liu Jinjing , Yu Xin , Li Chaoran , Wang Yi , Yu Weihong , Shen Min , Zheng Wenjie 

TITLE=Behçet's Syndrome in a Chinese Pedigree of NLRP3-Associated Autoinflammatory Disease: A Coexistence or Novel Presentation?

JOURNAL=Frontiers in Medicine

VOLUME=8

YEAR=2021

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2021.695197

DOI=10.3389/fmed.2021.695197

ISSN=2296-858X

ABSTRACT=<p><bold>Objectives:</bold><italic>NLRP3</italic>-associated autoinflammatory disease (<italic>NLRP3</italic>-AID) and Behçet's syndrome (BS) both belong to autoinflammatory diseases and rarely co-occur. Here we reported a Chinese pedigree of <italic>NLRP3</italic>-AID presented with BS.</p><p><bold>Methods:</bold> We recorded a Chinese pedigree of <italic>NLRP3</italic>-AID presented with BS. Whole-exome sequencing was performed to find the hereditary susceptibility gene, and Sanger sequencing was performed on a consecutive cohort of 30 BS patients. We also reviewed the English literature on vasculitis associated with <italic>NLRP3</italic>-AID.</p><p><bold>Results:</bold> The proband was a 45-year-old Chinese Han woman. She and her 12-year-old daughter presented with recurrent fevers, cold-induced urticaria, oral, and genital ulcers, conjunctivitis, uveitis, optic atrophy, erythema nodosum, headache, and hearing loss. They were initially suspected of having BS, and both responded poorly to corticosteroids and immunosuppressants, while anti-TNF therapy was moderately effective. Pedigree analysis revealed another four relatives with similar symptoms, and a heterozygous <italic>NLRP3</italic> gene mutation c.1316C&gt;T, p.Ala439Val was identified by whole-exome sequencing and Sanger sequencing. However, we did not discover <italic>NLRP3</italic> gene mutation by Sanger sequencing in a confirmative cohort of 30 BS cases. A few case reports of vasculitis coexisting with <italic>NLRP3</italic>-AID, including a case of glomerulonephritis, and five cases of retinal vasculitis, were summarized through literature review.</p><p><bold>Conclusions:</bold> Our study is the first report of <italic>NLRP3</italic>-AID associated with BS. The coexistence of <italic>NLRP3</italic>-AID and BS reveals the extensive heterogeneity of the pathogenesis of systemic autoinflammatory diseases and calls for specific therapeutics.</p>