Why the study?
Innate immune modulators show efficacy in idiopathic recurrent pericarditis (IRP), suggesting autoinflammation contributes to the disease, but the phenotype and genetic association with autoinflammatory disease genes remained to be characterized.
Are autoinflammatory disease genes associated with idiopathic recurrent pericarditis, and what is the clinical phenotype of these patients?
Are autoinflammatory disease genes associated with idiopathic recurrent pericarditis, and what is the clinical phenotype of these patients?
Idiopathic recurrent pericarditis is associated with variants in the MEFV gene and features of systemic inflammation, supporting the role of autoinflammation and the use of interleukin-1 targeted therapies to reduce corticosteroid dependence.
Answers are grounded in this paper and cite their sources.
MEFV variants may identify autoinflammatory IRP subsets; leaves open whether genetic testing or IL-1 inhibition improves outcomes.
Background Idiopathic recurrent pericarditis (IRP) is an orphan disease that carries significant morbidity, partly driven by corticosteroid dependence. Innate immune modulators, colchicine and anti-interleukin-1 agents, pioneered in monogenic autoinflammatory diseases, have demonstrated remarkable efficacy in trials, suggesting that autoinflammation may contribute to IRP. This study characterizes the phenotype of patients with IRP and monogenic autoinflammatory diseases, and establishes whether autoinflammatory disease genes are associated with IRP. Methods and Results We retrospectively analyzed the medical records of patients with IRP (n=136) and monogenic autoinflammatory diseases (n=1910) attending a national center (London, UK) between 2000 and 2021. We examined 4 genes (MEFV, MVK, NLRP3, TNFRSF1A) by next-generation sequencing in 128 patients with IRP and compared the frequency of rare deleterious variants to controls obtained from the Genome Aggregation Database. In this cohort of patients with IRP, corticosteroid dependence was common (39/136, 28.7%) and was associated with chronic pain (adjusted odds ratio 2.8 [95% CI, 1.3-6.5], P=0.012). IRP frequently manifested with systemic inflammation (raised C-reactive protein [121/136, 89.0%] and extrapericardial effusions [68/136, 50.0%]). Pericarditis was observed in all examined monogenic autoinflammatory diseases (0.4%-3.7% of cases). Rare deleterious MEFV variants were more frequent in IRP than in ancestry-matched controls (allele frequency 9/200 versus 2932/129 200, P=0.040). Conclusions Pericarditis is a feature of interleukin-1 driven monogenic autoinflammatory diseases and IRP is associated with variants in MEFV, a gene involved in interleukin-1β processing. We also found that corticosteroid dependence in IRP is associated with chronic noninflammatory pain. Together these data implicate autoinflammation in IRP and support reducing reliance on corticosteroids in its management.
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Peet et al. (2022) studied this question.
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