Differential expression of the inflammasome complex genes in systemic lupus erythematosus

Cruz, Heidi Lacerda Alves da; Cavalcanti, Catarina Addobbati Jordão; Silva, Jaqueline de Azevêdo; Lima, Camilla Albertina Dantas de; Fragoso, Thiago Sotero; Barbosa, Alexandre Domingues; Dantas, Andréa Tavares; Mariz, Henrique de Ataíde; Duarte, Ângela Luzia Branco Pinto; Pontillo, Alessandra; Crovella, Sérgio; Sandrin-Garcia, Paula

doi:10.1007/s00251-020-01158-6

Cited by 35 publications

(22 citation statements)

References 40 publications

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“…Cruz and colleagues with the evaluation of the NLRP3 variant in the Brazilian population demonstrated that gain of function allele (G) in rs10754558 was significantly higher in SLE patients with nephritis. 28 On the other hand, Su et al demonstrated that, at odds with our results, TT genotype in rs4612666 was correlated with severe disease activity in the Chinese population. Although in their study rs10754558 was not correlated with the risk of SLE, they reported that subjects with CC genotype in rs10754558 have a higher serum concentration of interferon-c (IFNc) and IL-1b.…”

Section: Discussioncontrasting

confidence: 94%

“…24,25 Besides, some previous association studies have demonstrated that NLRP3 variants are associated with the modulation of susceptibility, disease severity, and treatment efficacy of autoimmune diseases. [26][27][28][29] Functional analysis has revealed that some polymorphisms in this gene including rs4612666, rs10754558, and rs6672995 locate in the regulatory regions and correlate with the modulation of NLRP3 expression. [30][31][32][33][34] Therefore, regarding the previous data about the role of NLRP3 in SLE pathogenesis and related inflammatory processes, we hypostatized that these polymorphisms might be correlated with susceptibility and/or clinicopathological characteristics of SLE.…”

Section: Introductionmentioning

confidence: 99%

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Three functional variants in the NLRP3 gene are associated with susceptibility and clinical characteristics of systemic lupus erythematosus

Ehtesham

Rafie

Esmaeilzadeh

et al. 2021

Lupus

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Objective Nod-like receptor pyrin domain containing 3 ( NLRP3) gene encodes an intracellular receptor whose dysregulation in systemic lupus erythematosus (SLE) has been reported in multiple studies. Activation of NLRP3 inflammasome leads to the induction of inflammatory response via cleaving and producing of specific cytokines. In the present study, we assessed the possible association between three functional polymorphisms in this gene and SLE risk in the Iranian population. These variants include two gain of function (rs4612666 and rs10754558) and one loss of function (rs6672995) which are correlated with modulation of expression of NLRP3. Methods A case-control study involving 110 SLE patients and 116 control subjects was undertaken to estimate the frequency of rs4612666, rs10754558, and rs6672995 genotypes using real-time PCR high resolution melting method (HRM). Results Our findings revealed significant associations between GG genotype and G allele of rs10754558 with increased risk of SLE (OR for GG genotype= 2.82; 95%CI [1.45–5.46]/OR for G allele= 1.97; 95%CI [1.36–2.87]). Although, no significant associations were recognized between allele and genotype frequencies of rs4612666 and rs6672995 polymorphisms with SLE risk ( P > 0.05). Also, our analysis revealed that the C allele in rs4612666 and G allele in rs10754558 was correlated with the severity of disease activity (P < 0.001). Moreover, these common variants were associated with lower age of onset and some clinical symptoms in the patient group, such as skin manifestation, neurological symptom and, renal involvement (P < 0.05). Conclusion This study demonstrates a substantial association between NLRP3 polymorphisms with increased risk, clinical symptoms, and the severity of disease activity of SLE.

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Section: Discussioncontrasting

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Three functional variants in the NLRP3 gene are associated with susceptibility and clinical characteristics of systemic lupus erythematosus

Ehtesham

Rafie

Esmaeilzadeh

et al. 2021

Lupus

View full text Add to dashboard Cite

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“…At the same time, the activated caspase-1 fragment can induce cell membrane perforation, cell rupture, and cell pyroptosis (Fusco et al, 2020). Growing evidences indicate that NLRP3 inflammasome plays a key role in various AIDs (Shen et al, 2018;Zhao et al, 2018;Alves da Cruz et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Association of NLRP3 rs35829419 and rs10754558 Polymorphisms With Risks of Autoimmune Diseases: A Systematic Review and Meta-Analysis

Liang

2021

Front. Genet.

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The existing knowledge about the association between NLRP3 rs35829419/rs10754558 polymorphisms and susceptibility to autoimmune diseases (AIDs) remains controversial. Herein, a meta-analysis was performed to evaluate such association. We searched databases for relevant studies published in English up to February 2021. Stata14 was used to assess the odds ratio (OR). As for NLRP3 rs35829419, no significant association to overall AIDs was found in three genetic models [A vs. C: OR (95%CI) = 0.89 (0.69–1.14); AC vs. CC: 1.00 (0.77–1.30); AA/AC vs. CC: 0.93 (0.71–1.20)]. However, subgroup analysis by disease type showed that NLRP3 rs35829419 A allele may have a significant protective effect on rheumatoid arthritis (RA) susceptibility [A vs. C: 0.74 (0.57–0.96)]. NLRP3 rs10754558 polymorphism contributes to significantly reduce the risk of AIDs in the allelic model [G vs. C: 0.78 (0.71–0.87)], homozygote co-dominant model [GG vs. CC: 0.63 (0.51–0.77)], heterozygote co-dominant model [GC vs. CC: 0.78 (0.66–0.91)], dominant model [GG/GC vs. CC: 0.73 (0.63–0.84)], and recessive model [GG vs. GC/CC: 0.73 (0.62–0.88)]. In the subgroup analysis by ethnicity, association was observed between the NLRP3 rs10754558 G allele and AIDs in Latin Americans, but not in European, Arabian, or Asian populations. Stratification by disease type showed a significant association of the NLRP3 rs10754558 G allele with type 1 diabetes (T1D), RA, and systemic lupus erythematosus (SLE), but not with celiac disease (CD), multiple sclerosis (MS), or myasthenia gravis (MG). This meta-analysis suggests that the NLRP3 rs10754558, but not rs35829419, polymorphism is associated with susceptibility to AIDs, especially in Latin American individuals.

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“…Recent findings showed that NLRP3 and associated inflammatory cytokines, including IL-1β and IL-18, are elevated in the blood and nephritis biopsies from LN patients ( da Cruz et al, 2020 ; Huang et al, 2020 ). Moreover, to systematically explore the mechanisms of NLRP3 on LN, different mouse models have been analyzed.…”

Section: Role Of Nlrp3 In Lnmentioning

confidence: 99%

Role of NLRP3 Inflammasome in Lupus Nephritis and Therapeutic Targeting by Phytochemicals

Sun

et al. 2021

Front. Pharmacol.

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Systemic lupus erythematosus (SLE) is a multisystem autoimmune inflammatory condition that affects multiple organs and provokes extensive and severe clinical manifestations. Lupus nephritis (LN) is one of the main clinical manifestations of SLE. It refers to the deposition of immune complexes in the glomeruli, which cause kidney inflammation. Although LN seriously affects prognosis and represents a key factor of disability and death in SLE patients, its mechanism remains unclear. The NACHT, leucine-rich repeat (LRR), and pyrin (PYD) domains-containing protein 3 (NLRP3) inflammasome regulates IL-1β and IL-18 secretion and gasdermin D-mediated pyroptosis and plays a key role in innate immunity. There is increasing evidence that aberrant activation of the NLRP3 inflammasome and downstream inflammatory pathways play an important part in the pathogenesis of multiple autoimmune diseases, including LN. This review summarizes research progress on the elucidation of NLRP3 activation, regulation, and recent clinical trials and experimental studies implicating the NLRP3 inflammasome in the pathophysiology of LN. Current treatments fail to provide durable remission and provoke several sides effects, mainly due to their broad immunosuppressive effects. Therefore, the identification of a safe and effective therapeutic approach for LN is of great significance. Phytochemicals are found in many herbs, fruits, and vegetables and are secondary metabolites of plants. Evidence suggests that phytochemicals have broad biological activities and have good prospects in a variety of diseases, including LN. Therefore, this review reports on current research evaluating phytochemicals for targeting NLRP3 inflammasome pathways in LN therapy.

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Differential expression of the inflammasome complex genes in systemic lupus erythematosus

Cited by 35 publications

References 40 publications

Three functional variants in the NLRP3 gene are associated with susceptibility and clinical characteristics of systemic lupus erythematosus

Three functional variants in the NLRP3 gene are associated with susceptibility and clinical characteristics of systemic lupus erythematosus

Association of NLRP3 rs35829419 and rs10754558 Polymorphisms With Risks of Autoimmune Diseases: A Systematic Review and Meta-Analysis

Role of NLRP3 Inflammasome in Lupus Nephritis and Therapeutic Targeting by Phytochemicals

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