BackgroundChronic spontaneous urticaria (CSU) is a clinically heterogeneous inflammatory condition affecting the skin, in which mechanisms beyond histamine-mediated mast cell activation are increasingly recognized. Dysregulation of innate immune pathways, including inflammasome signaling, may contribute to disease pathogenesis.
Within the inflammasome family, NOD-like receptor pyrin domain–containing protein 3 (NLRP3) rs10754558 polymorphism has been implicated in altered cytokine responses in other inflammatory conditions. This study aimed to investigate the association between NLRP3 rs10754558 polymorphism and CSU susceptibility, and to examine its relationship with inflammasome-related cytokine responses (interleukin-1β [IL-1β] and IL-18).MethodsFifty-six patients with CSU and 56 age- and sex-matched healthy controls were recruited.
Genotyping of NLRP3 rs10754558 was performed. Whole blood cultures were stimulated with lipopolysaccharide (LPS) to assess IL-1β and IL-18 production.
Clinical and laboratory parameters, including the urticaria activity score (UAS7), autologous serum skin test (ASST) reactivity, erythrocyte sedimentation rate (ESR), and total serum IgE, were also evaluated.ResultsThe C allele of NLRP3 rs10754558 was significantly associated with increased CSU risk across multiple genetic models.
This study examined whether a common genetic variant in an inflammasome component, NLRP3 rs10754558, is linked to chronic spontaneous urticaria (CSU) susceptibility and to ex vivo production of inflammasome-associated cytokines.
The authors aimed to connect genotype to functional cytokine responses (interleukin‑1β and IL‑18) in patients and matched healthy controls.
A case‑control design enrolled 56 individuals with CSU and 56 age‑ and sex‑matched healthy volunteers.
Genotyping for NLRP3 rs10754558 was performed.
Whole blood was stimulated with lipopolysaccharide (LPS) to elicit cytokine release, and concentrations of IL‑1β and IL‑18 were measured.
Clinical and laboratory data collected included urticaria activity score (UAS7), autologous serum skin test (ASST) status, erythrocyte sedimentation rate (ESR), and total serum IgE.
Carriage of the C allele at rs10754558 was associated with increased odds of CSU under multiple genetic models.
Following LPS stimulation, CSU cases produced higher IL‑1β and IL‑18 than controls.
Individuals homozygous for the C allele (C/C) demonstrated the largest stimulated cytokine responses among genotype groups.
IL‑1β and IL‑18 responses were modestly positively correlated (reported r = 0.37).
Overall, the inflammasome‑related cytokine levels showed limited or inconsistent relationships with conventional measures of disease activity and serologic markers reported in the study.
The findings link a specific NLRP3 polymorphism with amplified systemic inflammasome‑related cytokine responsiveness in patients with CSU.
The results are associative and suggest a genetic contribution to innate immune reactivity in this heterogeneous disorder.
Direct evidence of NLRP3 inflammasome assembly or activation in lesional tissue or cells was not reported.
Causality cannot be inferred from the observed associations, and mechanistic confirmation was identified by the authors as not yet established.