Session Type: Abstract Submissions (ACR)
Background/Purpose . New data has emerged about the role of the inflammasome in psoriasis and psoriatic arthritis (PsA). The assembly of the inflammasome components in innate immune cells (monocytes) results in the rapid activation of Caspase-1, which cleaves pro-IL-1β and pro-IL-18 to generate active forms of these cytokines. We hypothesized that: “inflammasome activation occurs in monocytes, as a key element on the initiation and amplification of the innate immune response in PsA pathogenesis”. Therefore, it was decided: 1) To determine whether inflammasome activation occurs in monocytes of PsA patients and, 2) To determine the relationship between inflammasome activation with disease activity and metabolic syndrome in these patients.
Methods . After informed consent, 13 PsA patients (CASPAR criteria) and 16 age-matched healthy individuals attending to the outpatient Rheumatology clinic were enrolled. Demographic, laboratory and clinical data was recorded. Disease activity was determined by DAS-28 score. Blood pressure, diabetes history, lipid profile and waist circumference data were included. Metabolic syndrome (MS) was defined following the International Diabetes Federation (IDF) criteria. Purified monocytes were plated and stimulated for 18 h with LPS (100ng/ml) in presence or absence of Caspase-1 inhibitor. CD14 and Caspase-1 expression was analyzed by flow cytometry. Cell lysates and supernatants were collected for determination of Caspase-1 and NLRP3 protein by Western blot and cytokine levels by ELISA, respectively. Student’s ttest and Mann-Whitney tests were used for statistical analysis.
Results . Sixty two percent (62%) of patients were females, mostly (77%) Caucasians. The mean age was 45.15 (SD 9.7) years and mean disease duration was 6.7 (SD 5.5) years. Ten patients presented with active disease, mean DAS28 3.25 (SD 1.2). Metabolic syndrome was present in 77% of patients.
The percentage of CD14+/Caspase1+was numerically higher in PBMC-monocytes from PsA patients compared to normal controls (33.5 ± 13 vs. 22.5 ± 11.3, respectively), although difference did not reach statistical significance (p<0.1). Caspase-1 expression was confirmed by Western blot. No differences were found regarding cytokine levels. Purified monocytes from PsA patients displayed a robust inflammatory response after LPS stimulation where Caspase-1, NLRP3, IL-1β and IL-18 were highly expressed. Neither Caspase-1 nor cytokine expression were associated with disease activity. In a subset of PsA patients with MS, there was a trend to higher IL-1β levels (19.4 ± 24.8 vs. 4.1 ± 6.6) (p=0.08).
Conclusion . In this pilot study, PsA patients showed an enhanced expression of inflammasome activation, although difference did not reach statistical significance. Further studies including a larger number of patients are needed to truly establish a role of inflammasome activation in PsA pathogenesis and associated comorbidities.
R. Perez Alamino,
Genentech and Biogen IDEC Inc.,
L. R. Espinoza,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/is-there-a-role-for-inflammasome-activation-in-psa-pathogenesis-and-its-comorbidities/