Clinical characteristics of patients carrying the Q703K variant of the NLRP3 Gene: A 10-year multicentric national study

Aldo Naselli, Federica Penco, L. Cantarini, Antonella Insalaco, Mariolina Alessio, Alberto Tommasini, Cristina Maggio, Laura Piera Obici, Romina Gallizi, Marco A. Cimmino, Sara Signa, Orso Maria Lucherini, Sonia Carta, F. Caroli, Alberto Martini, Anna Rubartelli, Isabella Ceccherini, Marco Gattorno

Research output: Contribution to journalArticle

Abstract

Objective. The aim of our study was to analyze the clinical and functional effect of the p.Q703K (p. Q705K, c. 2107C> A) variant of the NLRP3 gene in a population of patients screened for suspected cryopyrin-associated periodic syndrome (CAPS). Methods. Since 2002, 580 patients underwent molecular analysis for NLRP3. Data on clinical presentation, response to treatment, and longterm followup were collected using a uniform questionnaire. The pattern of cytokine secretion after lipopolysaccharide stimulation from isolated monocytes was analyzed in 3 patients carrying the p.Q703K variant and 1 patient with a chronic infantile neurologic, cutaneous, articular syndrome phenotype carrying both the p.M406I and p.Q703K, and compared with 7 patients with CAPS with sure pathogenic variants and 6 healthy controls. Results. The p.Q703K variant was found in 57 screened patients with an overall allelic frequency of 5%. The frequency in normal controls was 5.5%. Clinical data at the moment of molecular analysis and at followup were available in 36 patients. Two patients displayed additional mutations of NLRP3. The mean followup was 2.5 years. Thirteen patients (39%) had a final diagnosis different from the original suspicion of CAPS. The remaining 21 patients displayed a mild phenotype mainly characterized by recurrent episodes of urticarial rash and arthralgia. Only 8 patients were treated with antiinterleukin (IL)-1 treatment, with a complete response in 5 patients. The pattern of secretion of IL-1β and other cytokines (IL-6 and IL-1 receptor antagonist) in patients did not display the aberrancies observed in patients with CAPS and was similar to that observed in healthy controls. Conclusion. The present study confirms the weak clinical and functional effect of the p.Q703K variant.

Original languageEnglish
Pages (from-to)1093-1100
Number of pages8
JournalJournal of Rheumatology
Volume43
Issue number6
DOIs
Publication statusPublished - Jun 1 2016

Fingerprint

antineoplaston A10
Cryopyrin-Associated Periodic Syndromes
Genes
Interleukin-1
Cytokines
Phenotype
Interleukin-1 Receptors
Arthralgia
Exanthema
Lipopolysaccharides
Monocytes
Interleukin-6

Keywords

  • Cryopyrin
  • Cryopyrin-Associated Periodic Syndrome
  • Inflammasome
  • Interleukin-1β
  • NLRP3

ASJC Scopus subject areas

  • Rheumatology
  • Immunology
  • Immunology and Allergy

Cite this

Clinical characteristics of patients carrying the Q703K variant of the NLRP3 Gene : A 10-year multicentric national study. / Naselli, Aldo; Penco, Federica; Cantarini, L.; Insalaco, Antonella; Alessio, Mariolina; Tommasini, Alberto; Maggio, Cristina; Obici, Laura Piera; Gallizi, Romina; Cimmino, Marco A.; Signa, Sara; Lucherini, Orso Maria; Carta, Sonia; Caroli, F.; Martini, Alberto; Rubartelli, Anna; Ceccherini, Isabella; Gattorno, Marco.

In: Journal of Rheumatology, Vol. 43, No. 6, 01.06.2016, p. 1093-1100.

Research output: Contribution to journalArticle

Naselli, A, Penco, F, Cantarini, L, Insalaco, A, Alessio, M, Tommasini, A, Maggio, C, Obici, LP, Gallizi, R, Cimmino, MA, Signa, S, Lucherini, OM, Carta, S, Caroli, F, Martini, A, Rubartelli, A, Ceccherini, I & Gattorno, M 2016, 'Clinical characteristics of patients carrying the Q703K variant of the NLRP3 Gene: A 10-year multicentric national study', Journal of Rheumatology, vol. 43, no. 6, pp. 1093-1100. https://doi.org/10.3899/jrheum.150962
Naselli, Aldo ; Penco, Federica ; Cantarini, L. ; Insalaco, Antonella ; Alessio, Mariolina ; Tommasini, Alberto ; Maggio, Cristina ; Obici, Laura Piera ; Gallizi, Romina ; Cimmino, Marco A. ; Signa, Sara ; Lucherini, Orso Maria ; Carta, Sonia ; Caroli, F. ; Martini, Alberto ; Rubartelli, Anna ; Ceccherini, Isabella ; Gattorno, Marco. / Clinical characteristics of patients carrying the Q703K variant of the NLRP3 Gene : A 10-year multicentric national study. In: Journal of Rheumatology. 2016 ; Vol. 43, No. 6. pp. 1093-1100.
@article{9e38217d61fd4d2baa921b3ae5ea8a0a,
title = "Clinical characteristics of patients carrying the Q703K variant of the NLRP3 Gene: A 10-year multicentric national study",
abstract = "Objective. The aim of our study was to analyze the clinical and functional effect of the p.Q703K (p. Q705K, c. 2107C> A) variant of the NLRP3 gene in a population of patients screened for suspected cryopyrin-associated periodic syndrome (CAPS). Methods. Since 2002, 580 patients underwent molecular analysis for NLRP3. Data on clinical presentation, response to treatment, and longterm followup were collected using a uniform questionnaire. The pattern of cytokine secretion after lipopolysaccharide stimulation from isolated monocytes was analyzed in 3 patients carrying the p.Q703K variant and 1 patient with a chronic infantile neurologic, cutaneous, articular syndrome phenotype carrying both the p.M406I and p.Q703K, and compared with 7 patients with CAPS with sure pathogenic variants and 6 healthy controls. Results. The p.Q703K variant was found in 57 screened patients with an overall allelic frequency of 5{\%}. The frequency in normal controls was 5.5{\%}. Clinical data at the moment of molecular analysis and at followup were available in 36 patients. Two patients displayed additional mutations of NLRP3. The mean followup was 2.5 years. Thirteen patients (39{\%}) had a final diagnosis different from the original suspicion of CAPS. The remaining 21 patients displayed a mild phenotype mainly characterized by recurrent episodes of urticarial rash and arthralgia. Only 8 patients were treated with antiinterleukin (IL)-1 treatment, with a complete response in 5 patients. The pattern of secretion of IL-1β and other cytokines (IL-6 and IL-1 receptor antagonist) in patients did not display the aberrancies observed in patients with CAPS and was similar to that observed in healthy controls. Conclusion. The present study confirms the weak clinical and functional effect of the p.Q703K variant.",
keywords = "Cryopyrin, Cryopyrin-Associated Periodic Syndrome, Inflammasome, Interleukin-1β, NLRP3",
author = "Aldo Naselli and Federica Penco and L. Cantarini and Antonella Insalaco and Mariolina Alessio and Alberto Tommasini and Cristina Maggio and Obici, {Laura Piera} and Romina Gallizi and Cimmino, {Marco A.} and Sara Signa and Lucherini, {Orso Maria} and Sonia Carta and F. Caroli and Alberto Martini and Anna Rubartelli and Isabella Ceccherini and Marco Gattorno",
year = "2016",
month = "6",
day = "1",
doi = "10.3899/jrheum.150962",
language = "English",
volume = "43",
pages = "1093--1100",
journal = "Journal of Rheumatology",
issn = "0315-162X",
publisher = "Journal of Rheumatology",
number = "6",

}

TY - JOUR

T1 - Clinical characteristics of patients carrying the Q703K variant of the NLRP3 Gene

T2 - A 10-year multicentric national study

AU - Naselli, Aldo

AU - Penco, Federica

AU - Cantarini, L.

AU - Insalaco, Antonella

AU - Alessio, Mariolina

AU - Tommasini, Alberto

AU - Maggio, Cristina

AU - Obici, Laura Piera

AU - Gallizi, Romina

AU - Cimmino, Marco A.

AU - Signa, Sara

AU - Lucherini, Orso Maria

AU - Carta, Sonia

AU - Caroli, F.

AU - Martini, Alberto

AU - Rubartelli, Anna

AU - Ceccherini, Isabella

AU - Gattorno, Marco

PY - 2016/6/1

Y1 - 2016/6/1

N2 - Objective. The aim of our study was to analyze the clinical and functional effect of the p.Q703K (p. Q705K, c. 2107C> A) variant of the NLRP3 gene in a population of patients screened for suspected cryopyrin-associated periodic syndrome (CAPS). Methods. Since 2002, 580 patients underwent molecular analysis for NLRP3. Data on clinical presentation, response to treatment, and longterm followup were collected using a uniform questionnaire. The pattern of cytokine secretion after lipopolysaccharide stimulation from isolated monocytes was analyzed in 3 patients carrying the p.Q703K variant and 1 patient with a chronic infantile neurologic, cutaneous, articular syndrome phenotype carrying both the p.M406I and p.Q703K, and compared with 7 patients with CAPS with sure pathogenic variants and 6 healthy controls. Results. The p.Q703K variant was found in 57 screened patients with an overall allelic frequency of 5%. The frequency in normal controls was 5.5%. Clinical data at the moment of molecular analysis and at followup were available in 36 patients. Two patients displayed additional mutations of NLRP3. The mean followup was 2.5 years. Thirteen patients (39%) had a final diagnosis different from the original suspicion of CAPS. The remaining 21 patients displayed a mild phenotype mainly characterized by recurrent episodes of urticarial rash and arthralgia. Only 8 patients were treated with antiinterleukin (IL)-1 treatment, with a complete response in 5 patients. The pattern of secretion of IL-1β and other cytokines (IL-6 and IL-1 receptor antagonist) in patients did not display the aberrancies observed in patients with CAPS and was similar to that observed in healthy controls. Conclusion. The present study confirms the weak clinical and functional effect of the p.Q703K variant.

AB - Objective. The aim of our study was to analyze the clinical and functional effect of the p.Q703K (p. Q705K, c. 2107C> A) variant of the NLRP3 gene in a population of patients screened for suspected cryopyrin-associated periodic syndrome (CAPS). Methods. Since 2002, 580 patients underwent molecular analysis for NLRP3. Data on clinical presentation, response to treatment, and longterm followup were collected using a uniform questionnaire. The pattern of cytokine secretion after lipopolysaccharide stimulation from isolated monocytes was analyzed in 3 patients carrying the p.Q703K variant and 1 patient with a chronic infantile neurologic, cutaneous, articular syndrome phenotype carrying both the p.M406I and p.Q703K, and compared with 7 patients with CAPS with sure pathogenic variants and 6 healthy controls. Results. The p.Q703K variant was found in 57 screened patients with an overall allelic frequency of 5%. The frequency in normal controls was 5.5%. Clinical data at the moment of molecular analysis and at followup were available in 36 patients. Two patients displayed additional mutations of NLRP3. The mean followup was 2.5 years. Thirteen patients (39%) had a final diagnosis different from the original suspicion of CAPS. The remaining 21 patients displayed a mild phenotype mainly characterized by recurrent episodes of urticarial rash and arthralgia. Only 8 patients were treated with antiinterleukin (IL)-1 treatment, with a complete response in 5 patients. The pattern of secretion of IL-1β and other cytokines (IL-6 and IL-1 receptor antagonist) in patients did not display the aberrancies observed in patients with CAPS and was similar to that observed in healthy controls. Conclusion. The present study confirms the weak clinical and functional effect of the p.Q703K variant.

KW - Cryopyrin

KW - Cryopyrin-Associated Periodic Syndrome

KW - Inflammasome

KW - Interleukin-1β

KW - NLRP3

UR - http://www.scopus.com/inward/record.url?scp=84973303603&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84973303603&partnerID=8YFLogxK

U2 - 10.3899/jrheum.150962

DO - 10.3899/jrheum.150962

M3 - Article

VL - 43

SP - 1093

EP - 1100

JO - Journal of Rheumatology

JF - Journal of Rheumatology

SN - 0315-162X

IS - 6

ER -