Does IL33/Sst2 Pathway Play a Role in the Pathogenesis of Familial Mediterranean Fever?

Abstract

Objectives: Interleukin-33 (IL-33) is a novel cytokine which belongs to IL-1 superfamily. It shares structural homology and common signaling pathway with IL-1β whose excessive secretion results in Familial Mediterranean Fever (FMF). In this study, we aimed to evaluate the serum IL-33 and its decoy receptor sST2 levels in patients with FMF and its correlation with disease activity. Materials and Methods: In this cross-sectional single-centered study, 76 FMF patients and 30 age- and sex-matched healthy individuals were recruited. Disease activity was evaluated according to the autoinflammatory disease activity index, in which ≥9 points were considered as “active disease”. Serum IL-33 and sST2 levels were measured using a commercial enzyme-linked immunosorbent assay kit. A p-value <0.05 was considered statistically significant. Results: Serum IL-33 and sST2 levels were similar in both groups (p=0.899 and p=0.614, respectively). Similarly, there were no statistically significant differences between active (n=24) and inactive (n=52) patients; however, serum C-reactive protein and amyloid-A levels were significantly higher in active FMF patients (p=0.001 and p=0.002, respectively). Conclusion: This study has revealed that even though IL-33 is similar with IL-1β in terms of structure and signaling, it neither increased in sera of FMF patients nor correlated with disease activity. In contrast to previous studies conducted on autoimmune diseases, the role of IL33/sST2 pathway in autoinflammatory diseases needs to be further evaluated.

Keywords

• Familial Mediterranean Fever
• Interleukin-1β
• Interleukin-33
• sST2

Ailevi Akdeniz Ateşi Patogenezinde IL33/sST2 Yolağı Rol Oynamakta mıdır?

Abstract

Amaç: İnterlökin-33 (IL-33); IL-1 süper ailesine ait yeni bir sitokindir. Ailevi Akdeniz Ateşi (FMF) patogenezinde yer alan IL-1β ile benzer yapısal ve sinyalizasyon yolağına sahiptir. Bu çalışmada, FMF hastalarının serumlarında IL-33 ve bunun reseptörü olan sST2 reseptör seviyelerinin ve hastalık aktivitesi ile ilişkisinin incelenmesi amaçlanmıştır. Gereç ve Yöntem: Tek merkezli kesitsel olan bu çalışmaya, 18 yaş ve üzeri 76 FMF hastası ile yaş ve cinsiyet uyumlu 30 sağlıklı bireyler dahil edildi. Hastalık aktivitesi oto-enflamatuvar hastalık aktivite indeksi skoru kullanılarak değerlendirilmiş olup ≥9 puan aktif hastalık olarak kabul edildi. Serum IL-33 ve sST2 seviyeleri enzyme-linked immunosrobent assay kullanılarak çalışıldı. P-değeri <0,05 istatistiksel olarak anlamlı kabul edildi. Bulgular: Serum IL-33 ve sST2 değerleri, FMF hastaları ve sağlıklı kontrol grubunda benzer bulundu [sırasıyla (p=0,899 ve p=0,614)]. Aktif (n=24) ve inaktif (n=52) FMF hastaları arasında da serum IL-33 ve sST2 değerleri arasında fark bulunamadı. Ancak, aktif FMF hastalarında serum C-reaktif protein ve serum amiloid A düzeylerinin inaktif hastalara göre istatistiksel olarak anlamlı bir şekilde daha yüksek olduğu görüldü (sırasıyla, p=0,001 ve p=0,002). Sonuç: Bu çalışmada, her ne kadar IL-33, IL-1β ile benzer yapıya ve sinyalizasyon yolağına sahip olsa da FMF hastalarında serum düzeylerinin artmadığı ve hastalık aktivitesi ile de ilişkili olmadığı gösterilmiştir. Otoimmün hastalıklarla yapılan çalışmaların aksine, IL33/sST2 yolağının otoenflamatuvar hastalıklardaki rolünün ileri çalışmalarla incelenmesi gerekmektedir.

Keywords

• Ailevi Akdeniz Ateşi
• İnterlökin-1β
• İnterlökin-33
• sST2

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