AB0034 NLRP12 GENE VARIANTS AND AUTOINFLAMMATORY DISEASES IN A GREEK PATIENT COHORT
Authors: S. Ziaragkali, V. Papatheodorou, A. Karamanakos, O. Vougiouka, E. Sapountzi, A. Germenis, M. G. Tektonidou, P. P. Sfikakis, K. Laskari
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Variants in the <i>NLRP12</i> gene cause rare autosomal dominant <i>NLRP12</i>-associated autoinflammatory disease (<i>NLRP12</i>-AID). So far, a few patients with <i>NLRP12</i>-AID have been described worldwide; therefore, data on the clinical phenotype and genetic profile are limited [1,2]. <h3>Objectives:</h3> To estimate the prevalence of <i>NLRP12</i> variants in a cohort of Greek patients with systemic autoinflammatory diseases (SAIDs) and describe their disease phenotypic expression. <h3>Methods:</h3> Consecutive patients (n=167) with confirmed SAIDs who underwent screening by next generation sequencing targeting 26 SAID-associated genes, including <i>NLRP12,</i> were included in this study. The demographic, clinical and laboratory parameters of those carrying at least one <i>NLRP12</i> gene variant were recorded. <h3>Results:</h3> A total of 16 out of 167 patients yielded at least one <i>NLRP12</i> variant. All but three patients carried a coexisting variant in at least one of 12 other SAID-related genes, namely <i>MEFV</i>, <i>TNFRSF1A</i>, <i>NLRP3</i>, <i>NLRP7</i>, <i>MVK</i>, <i>IL36RN, IL1RN</i>, <i>AP1S3</i>, <i>LPIN2, PLCG2, SH3BP2</i> and <i>CARD14</i>. <i>NLRP12</i>-AID was identified as the underlying autoinflammatory disorder in 13 out of the 16 patients with <i>NLRP12</i> variants, while the remaining patients were diagnosed with adult-onset Still's disease (n=2) or inflammatory bowel disease. <i>NLRP12</i>-AID patients (8 females), aged (mean) 17 years at disease onset, suffered from recurrent (mean 4 attack/year) disease episodes lasting (mean) 10 days. Most frequent manifestations included high grade fever (85%), gastrointestinal involvement (62% - abdominal pain, n=6; vomiting, n=5; diarrhea, n=3; oral ulcers, n=3; aseptic peritonitis, n=2), arthralgias/arthritis (54%), and organomegaly (54%), whereas serositis (pericarditis, n=5; pleuritis, n=1), malaise, sore throat, lymphadenopathy and/or neurological complications (headache, n=5; aseptic meningitis, n=1; increased intracranial pressure, n=1) occurred in 38% of the patients. Almost one-third (31%) presented with maculopapular rash and/or myalgias, and less frequent features included periorbital edema (8%), and conjunctivitis (8%). All but one patient had elevated inflammatory markers (92%), and leukocytosis was observed in 62%. Most patients responded well to non-steroidal anti-inflammatory drugs (n=7/10), corticosteroids (n=5/7), and/or anti-IL1 agents (n=3/5). One patient was treated with an TNFa-inhibitor with good response, while the response to colchicine was scarce (n=1/4). <h3>Conclusion:</h3> In our Greek SAID cohort, <i>NLRP12</i>-AID occurred in 8% of patients, manifested both in childhood and adulthood, and was characterized by a remarkable phenotypic diversity. Further studies should validate combined molecular and clinical data to better understand this distinct nosological entity. <h3>REFERENCES:</h3> [1] Jéru I, et al. Mutations in NALP12 cause hereditary periodic fever syndromes. <i>Proc Natl Acad Sci U S A</i>. 2008;105(5):1614-1619. [2] Miao J, et al. <i>NLRP12</i>-associated autoinflammatory disease in Chinese adult patients: a single-centre study. <i>RMD Open</i>. 2023;9(4):e003598. <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>