A 54-year-old man with a university degree was admitted to our hospital because of a two-year history of progressive dementia. He had familial sensorineural hearing loss and had been treated for epilepsy since his 30s. On admission, he showed severe dementia and parkinsonism without fever or skin rash. Systemic inflammation was evident, and the CSF cell count and IL-6 level were elevated to 53/μl and 307 ‍pg/ml, respectively. Brain MRI demonstrated diffuse brain atrophy. More detailed anamnesis revealed a history of rheumatoid arthritis in childhood and aseptic meningitis in his 20s. Genetic examination for autoinflammatory diseases demonstrated compound heterozygotic mutations in the NLRP3 gene, causing cryopyrin-associated periodic fever syndrome (CAPS). This case was atypical CAPS presenting as early-onset progressive dementia, without recurrent fever or urticaria-like eruption which are usually seen in this disease.

UNASSIGNED: Chronic obstructive pulmonary disease (COPD) is a chronic respiratory ailment influenced by a blend of genetic and environmental factors. Inflammatory response and an imbalance in oxidative-antioxidant mechanisms constitute the primary pathogenesis of COPD. Glutathione S-transferase P1(GSTP1) plays a pivotal role as an antioxidant enzyme in regulating oxidative-antioxidant responses in the pulmonary system. The activation of the NOD-like receptor thermal protein domain (NLRP3) inflammatory vesicle can trigger an inflammatory response. Several investigations have implicated GSTP1 and NLRP3 in the progression of COPD; nonetheless, there remains debate regarding this mechanism.
UNASSIGNED: Employing a case-control study design, 312 individuals diagnosed with COPD and 314 healthy controls were recruited from Gansu Province to evaluate the correlation between GSTP1 (rs4147581C>G and rs1695A>G) and NLRP3 (rs3806265T>C and rs10754558G>C) polymorphisms and the susceptibility to COPD.
UNASSIGNED: The presence of the GSTP1 rs4147581G allele substantially elevated the susceptibility to COPD (CGvs.CC:OR=3.11,95% CI=1.961-4.935, P<0.001;GGvs.CC:OR=2.065,95% CI=1.273-3.350, P=0.003; CG+GGvs.CC:OR=2.594,95% CI=1.718-3.916, P<0.001). Similarly, the NLRP3rs3806265T allele significantly increased the susceptibility to COPD (TC:TT:OR=0.432,95% CI=0.296-0.630; TC+CCvs.TT:OR=2.132,95% CI=1.479-3.074, P<0.001). However, no statistically significant association was discerned between the rs1695A>G and rs10754558G>C polymorphisms and COPD susceptibility (P>0.05).
UNASSIGNED: In summary, this study ascertained that the GSTP1 rs4147581C>G polymorphism is associated with increased COPD susceptibility, with the G allele elevating the risk of COPD. Similarly, the NLRP3 rs3806265T>C polymorphism is linked to elevated COPD susceptibility, with the T allele heightening the risk of COPD.

Neonatal-onset multisystem inflammatory disease (NOMID) is a rare and severe autoinflammatory disease caused by mutations of the NLRP3 gene and is characterized by a skin rash, fever, arthropathy, and neurologic manifestations. We herein report a neonatal case with recurrent rash, fever, and meningitis from 12 h after birth, and NOMID was diagnosed during the neonatal period. We also reviewed the clinical characteristics and genetic mutations of previously reported Chinese neonates with NOMID.
NOMID is rare in China, and there have been over 100 cases uncovered thus far, including ours. The patient we reported here was the youngest among the confirmed Chinese cases and had the de novo mutation c.1210G>C (p.V404L) in exon 4 of the NLRP3 gene, which has not been reported previously. All 25 patients manifested recurrent urticaria-like rash, and 24 were febrile. Of the 23 patients with genetic data available, all had NLRP3 mutations. The primary treatment of these patients entailed glucocorticoids and immunosuppressants; however, the IL-1 inhibitor was rarely used due to its current unavailability in China. One patient was cured by umbilical cord blood stem cell transplantation (UCBT), which provided an alternative treatment.
We recommend that NOMID be considered for neonates with recurrent rash, fever, and aseptic meningitis. However, further research on underlying mechanisms and therapeutic regimens in China is necessary to provide improved management.

BACKGROUND: High mobility group box-1 (HMGB1) is an endogenous danger signal that mediates activation of the innate immune response including NLR pyrin domain containing 3 (NLRP3) inflammasome activation and proinflammatory cytokine release. Although HMGB1 and NLRP3 have been implicated in the pathophysiology of seizures, the correlation between HMGB1 and NLRP3 expression has not been determined in children with febrile seizures (FS). To explore the relationship between extra-cellular HMGB1 and NLRP3 in children with FS, we analyzed serum HMGB1, NLRP3, caspase-1, and proinflammatory cytokines in patients with FS.
METHODS: Thirty children with FS and thirty age-matched febrile controls were included in this study. Blood was obtained from the children with FS within 1 h of the time of the seizure; subsequently, the serum contents of HMGB1, NLRP3, caspase-1, interleukin (IL)-1β, interleukin (IL)-6, and tumour necrosis factor-α (TNF-α) were determined by enzyme-linked immunosorbent assay. The Mann‒Whitney U test was used to compare serum cytokine levels between FS patients and controls. Spearman\'s rank correlation coefficient was calculated to detect significant correlations between cytokine levels.
RESULTS: Serum levels of HMGB1, NLRP3, caspase-1, IL-1β, IL-6, and TNF-α were significantly higher in FS patients than in febrile controls (p < 0.05). Serum levels of HMGB1 were significantly correlated with levels of NLRP3 and caspase-1 (both, p < 0.05). Serum levels of caspase-1 were significantly correlated with levels of IL-1β (p < 0.05). Serum levels of IL-1β were significantly correlated with levels of IL-6 and TNF-α (p < 0.05).
CONCLUSIONS: HMGB1 is up-regulated in the peripheral serum of FS patients, which may be responsible, at least in part, for the increased expression of NLRP3 and Caspase-1. Increased expression of caspase-1 was significantly associated with elevated serum levels of IL-1β. Given that activated Caspase-1 directly regulates the expression of mature IL-1β and positively correlates with activation of the NLRP3 inflammasome, our data suggest that increased levels of peripheral HMGB1 possibly mediate IL-1β secretion through the activation of the NLRP3 inflammasome in children with FS. Thus, both HMGB1 and NLRP3 might be potential targets for preventing or limiting FS.

Cryopyrin-associated periodic syndromes (CAPS) have been considered autoinflammatory diseases resulting from NLRP3 gene mutations. In recent years, these conditions have been redefined as NLRP3-associated autoinflammatory diseases (NLRP3-AID). Our previous study highlighted a case of a Chinese individual carrying the de novo NLRP3 mutation.
A female child carrying a de novo variant (c.1718T>G, p. L573W) in the NLRP3 gene was presented in this work. The patient manifested various symptoms, including recurrent fever, a rash resembling urticaria, arthritis, physical growth retardation, a notable prominence of the forehead, and a flat nose bridge. Additionally, inflammatory markers, like WBC count, PLT count, CRP, ESR, and IL-6 showed elevated levels. Additionally, we observed interstitial pulmonary disease in the patient, which is not frequently mentioned in previous studies. Notably, the proband did not present with any ocular, auditory, or neurological symptoms. After 12 weeks of subcutaneous canakinumab injection, there was a clear improvement in the patient\'s clinical manifestations and inflammatory markers.
Our study contributes to broadening the clinical spectrum of established pathogenic variants of NLRP3 gene, which are related to NLRP3-AID.

BACKGROUND: The goal of this case-control observational study was to compare the levels of the human nucleotide-binding domain, leucine-rich repeat, and pyrin domain-containing-3 (NLRP3) protein in the saliva and gingival crevicular fluid (GCF) of patients with symptomatic irreversible pulpitis (SIP) and healthy controls.
METHODS: The 16 patients in the control group were matched with the 16 patients in the SIP group to create a total of 32 patients. In addition to saliva, GCF (n = 48) samples were collected from the involved tooth (n = 16), contralateral tooth (n = 16), and adjacent tooth (n = 16) in the SIP group. Saliva and GCF were taken from the healthy group as a baseline. An independent t-test was used for statistical analysis. The random-intercept model was used to compare the average NLRP3 levels in the SIP tooth, adjacent tooth, and contralateral tooth taking age as a covariate, and the P value was adjusted using Bonferroni correction.
RESULTS: There were significantly higher levels of NLRP3 in the saliva of SIP patients (1.78 ± 1.14 ng/ml) compared to the healthy control (0.70 ± 0.70 ng/ml) and in the GCF of the involved tooth (5.72 ± 0.63 ng/ml) compared to healthy people (1.60 ± 0.42 ng/ml) (P < .001). In SIP patients the mean difference of NLRP3 levels between SIP and contralateral teeth was significant at 4.13 ng/ml (95% confidence interval, 3.52-4.70 P < .001) and a mean difference between adjacent teeth and contralateral teeth was significant at 3.53 ng/ml [95% confidence interval, 2.94-4.12 P < .001]. The NLRP3 in GCF and saliva had a negative association in the affected tooth but a negligible correlation in healthy controls.
CONCLUSIONS: The NLRP3 inflammasome has the potential to be employed as a molecular diagnostic biomarker for pulpal disorders.

BACKGROUND: Cryopyrin-associated periodic syndrome (CAPS), a rare genetic autoimmune disease, is composed of familial cold autoinflammatory syndrome (FCAs), Muckle-Wells syndrome (MWS), and neonatal onset multisystem inflammatory disease (NOMID). MWS is caused by dominantly inherited or de novo gain-of-function mutations in the NOD-like receptor 3 (NLRP3) gene. At present, there is no report about the variation of R262W in China.
METHODS: We reported a 3-year-old Chinese boy who had recurrent fever without obvious inducement, bilateral conjunctival congestion, and urticarial-like rash. Laboratory examination showed elevation in leukocyte count, neutrophil count, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) and serum amyloid protein (SAA) levels. Whole exome sequencing identified a missense variation c.784-786delinsTGG (p.R262W) in the coding region of the NLRP3 gene.
CONCLUSIONS: A classical variant of the NLRP3 gene in a patient with MWS was first reported in China.

Genetic factors are important risk factors for asthma. Nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) is closely associated with asthma. Mitochondrial antiviral signaling protein (MAVS) mediates the recruitment of NLRP3 to the mitochondria and activation of the NLRP3 inflammasome. The purpose of this study was to analyze the effects of NLRP3 and MAVS polymorphisms on the risk of asthma and the interactions between them. Children with asthma (n = 127) and healthy children (n = 100) were recruited between August, 2020 and July, 2021. Multiplex polymerase chain reaction and sequencing was used to analyze genotypes of single nucleotide polymorphisms. The multifactor dimensionality reduction statistical method was used to detect and model epistasis of gene-gene interactions. There were significant differences in the distribution of MVAS rs6515831 and NLRP3 rs10925023 genotypes between the asthma and healthy groups. Compared with rs6515831 TT genotype, the results showed that rs6515831CT genotype increased the risk of asthma (odds ratio: 2.243, 95% CI: 1.221-4.122, P = .009). Compared with rs10925023 GG genotype, the results showed that the risk of asthma in the population with rs10925023 TT genotype was lower (odd ratio: 0.643, 95% CI: 0.423-0.979, P = .039). In the genotype of the NLRP3 rs12048215 locus, the IgE level of asthma patients with genotype AG was lower than that of patients with genotype AA. The dendrogram model showed the strongest interaction between rs7272495 and rs10925023, which was expressed in a synergistic manner. Haplotype analysis revealed that rs10925023T/rs7272495G and rs10925023T/rs3272495A were statistically different in distribution between the two groups. The MAVS rs6515831 and NLRP3 rs10925023 polymorphisms were associated with the risk of asthma in children. There may be interactions between NLRP3 and MAVS polymorphisms in the risk of asthma.

COPD is a complex respiratory disease characterized by chronic airway inflammation and the airflow limitations are not fully reversible due to the combination of genetic and environmental factors. Genetic factors such as polymorphisms, may affect the susceptibility of COPD. In the present study, we examined the association between the polymorphisms of three genes and COPD risk in a Chinese Han population.
A total of 375 COPD patients and 284 control subjects were recruited from November 2018 to June 2021. Data on demographic basic information, smoking status, history of coal dust exposure, and peripheral blood were collected from subjects of two groups. Three polymorphisms (NLRP3 rs1539019, LAMB1 rs4320486,  IL-6 rs1800796) were analyzed. Logistic analysis was used to evaluate the genetic contribution of selected SNPs to COPD susceptibility.
The AC genotype of NLRP3 rs1539019 significantly decreased COPD risk compared with CC genotype (adjusted OR = 0.508, 95% CI 0.336-0.767). In the stratification analyses, the AC genotype significantly decreased the risk of COPD in subjects aged 60 and over (p=0.005; adjusted OR = 0.553; 95% CI 0.366-0.835) with current smoking status (p=0.002; adjusted OR = 0.419; 95% CI 0.240-0.732) when compared with AA+CC genotype. Moreover, a significantly decreased risk for GOLD III COPD was found in genotype AC of NLRP3 rs1539019 (p=0.006; adjusted OR = 0.502; 95% CI 0.306-0.822).
Our present study revealed that the genotype AC of NLRP3 rs1539019 is related to a decreased risk of COPD in a Chinese Han population, a large-sample, multi-center, multi-ethnic study is needed to further confirm our study.

UNASSIGNED: This study aimed to evaluate the gene expression of the P2X purinoceptor 7 (P2X7R)- nod-like receptor pyrin domain-containing protein 3 (NLRP3) signal pathway in peripheral blood mononuclear cells (PBMCs) between schizophrenia (SCZ) patients and healthy controls (HC) to reveal its relationship with clinical variables.
UNASSIGNED: Thirty-two SCZ patients and 41 healthy controls were included in this study. The Scale for the Assessment of Positive Symptoms (SAPS) and the Scale for the Assessment of Negative Symptoms (SANS), The Global Assessment of Functioning (GAF) scale and the Functioning Assessment Short Test (FAST) scales were applied. P2X7R, NLRP3, IL-1β and IL-18 gene expression levels were evaluated by real-time polymerase chain reaction in PBMCs.
UNASSIGNED: NLRP3, P2RX7, IL-1β and IL-18 expression levels were significantly higher in PBMCs of SCZ patients than in HC subjects. Negative correlations were found between NLRP3 gene expression levels and GAF and FAST scales scores. There was a negative correlation between IL-18 expression levels and the GAF and FAST scales scores and a positive correlation with the SAPS scale scores.
UNASSIGNED: Systemic inflammation is implicated in SCZ pathogenesis, according to our findings, which suggest that the NLRP3 pathway may be involved. The NLRP3 inflammasome may serve as a biomarker for SCZ, and its pharmacological regulation may be a promising treatment approach.Key pointsWe hypothesised that the NLRP3 pathway may contribute to the etiopathogenesis of schizophrenia.NLRP3, IL-1β and IL-18 mRNA levels were higher in patients with schizophrenia compared to healthy controls.Negative correlations were found between NLRP3 gene expression levels and GAF and FAST scales scores.There was a negative correlation between IL-18 expression levels and the GAF and FAST scales scores.The SAPS scale scores and IL-18 expression levels had a positive correlation.Given all these findings, it can be stated that NLRP3 inflammasome may play a role in the pathogenesis and symptoms of schizophrenia.