NLRP12-associated autoinflammatory disease in Chinese adult patients: a single-centre study

RMD Open. 2023 Dec 20;9(4):e003598. doi: 10.1136/rmdopen-2023-003598.

Abstract

Background: NLRP12-associated autoinflammatory disease (NLRP12-AID) is an autosomal dominant autoinflammatory disorder caused by variants of NLRP12 gene. We aimed to report a cohort of Chinese adult patients with NLRP12-AID and summarised phenotypes and genotypes.

Methods: Twenty patients were diagnosed with NLRP12-AID after performing whole-exome sequencing and were included in our cohort. Demographic information, clinical data and treatment response were collected and evaluated. A literature review of NLRP12-AID was performed, and the clinical features and mutated sites were summarised and compared with our cohort.

Results: Among the 20 NLRP12-AID patients, the main clinical features of NLRP12-AID included fever, cutaneous rash, arthralgia/arthritis, pharyngitis/tonsillitis, lymphadenopathy, myalgia and abdominal pain/diarrhoea. Thirteen NLRP12 variants were detected as F402L, G39V, R1030X, R7G, E24A, Q90X, A218V, A259V, W581X, G729R, R859W, c.-150T>C and c.*126G>C. Glucocorticoids were used in 14 patients, immunosuppressive agents in 13, and tocilizumab in 2. Seventeen patients had good responses to therapy. When compared with 50 NLRP12-AID patients from other countries, Chinese patients had fewer variants in exon 3, higher incidences of cutaneous rash, pharyngitis/tonsillitis and lymphadenopathy. Among all these 70 NLRP12-AID patients, patients carrying non-exon-3 variants had higher frequencies of ocular involvement, pharyngitis/tonsillitis, headache and lymphadenopathy than those with exon-3 variants.

Conclusion: This is the largest cohort of NLRP12-AID in the world and seven novel variants of NLRP12 were identified. Chinese adult patients of NLRP12-AID had more non-specific symptoms such as pharyngitis/tonsillitis and lymphadenopathy when compared with patients from other countries, for which the less occurrence of exon-3 variants might be one possible reason.

Keywords: Immune Complex Diseases; Immune System Diseases; Inflammation.

Publication types

  • Review

MeSH terms

  • Adult
  • China / epidemiology
  • Exanthema* / etiology
  • Hereditary Autoinflammatory Diseases* / diagnosis
  • Hereditary Autoinflammatory Diseases* / drug therapy
  • Hereditary Autoinflammatory Diseases* / genetics
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / therapeutic use
  • Lymphadenopathy* / complications
  • Mutation
  • Pharyngitis* / complications
  • Tonsillitis* / complications

Substances

  • NLRP12 protein, human
  • Intracellular Signaling Peptides and Proteins