Sistemik lupus eritematozusta tip I interferon cevabı ve kompleman aktivasyonunun klinik bulgularla ilişkisi
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Dosyalar
Tarih
2015
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Trakya Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Sistemik lupus eritematozus, organ ve hücrelerin doku bağlayıcı otoantikorlar ve immün kompleksler aracılığı ile hasar gördüğü kronik otoimmün bir hastalıktır. Kompleman sistemi birçoğu proteinaz olan 30’dan fazla proteinin bir kompleks serisi oluşturmasından meydana gelir. Kompleman sisteminin sistemik lupus eritematozus patogenezinde hem olumlu hem de olumsuz etkileri bulunur. Son dönemde sistemik lupus eritematozuslu hastalarda kompleman aktivasyonunu değerlendirmek için farklı biomarkerlerin tanımlanması gündeme gelmiştir. Bunun yanında kompleman aktivasyonu muhtemelen sistemik lupus eritematozus patogenezinde de rol oynadığı için kompleman sistemi sistemik lupus eritematozusun geleceği yönelik tedavi planlanmasında hedef bir yolak da olabilir. Çalışma kapsamında sistemik lupus eritematozuslu hastalarda tip I interferon cevabını belirlemek için son dönemde tip I interferon cevabı ile ilişkili bulunan CXCL-12, CXCL-10 (IP-10) ve nötrofil aktivasyonu ilişkili LL-37 ve yeni tedavi hedefi olan BAFF düzeylerinin değerlendirilmesi planlandı. Çalışmamızda Trakya Üniversitesi Tıp Fakültesi Romatoloji bölümünde takipli sistemik lupus eritematozuslu 94 hasta (88 kadın, 6 erkek) ve 101 kontrol olgusu (87 kadın, 14 erkek) alındı. Çalışmamız sonuçlarında sistemik lupus eritematozuslu hastalarda kontrol grubu ile karşılaştırıldığında; SDF-1, CXCL-10, Complement fragments Bb değerlerinin anlamlı olarak (p<0.05) yüksek ; C3a des-arg ve LL37 değerlerinin ise anlamlı olarak (p<0.05) düşük olduğu ancak Ficolin ve BAFF değerlerinde ise hasta ve kontrol grubu arasında anlamlı fark olmadığı görülmüştür. SLEDAI skoru 6 ve üzerinde olan hastalar aktif kabul edildi. Karşılaştırma sonucunda aktif ve inaktif SLE’li hastalarda SDF-1, BAFF, C3a-des-arg, Complement Fragments Bb, Ficolin ve LL37 değer ortalamaları arasında anlamlı fark bulunamadı. Aktif hastalığı olan grupta CXCL10 düzeyleri inaktif hastalığı olan gruba göre anlamlı olarak yüksek idi (p=0.023). Artritli hastalarda SDF-1, BAFF, CXCL10 ve complement fragments Bb ortalama değerlerinde anlamlı yükseklik olduğu bulundu (sırasıyla p=0.003, p=0.030, p=0.001). Nörolojik tutulum olan ve olmayan SLE’liler karşılaştırıldığında C3a des-arg düzeyinin nörolojik tutulumlu SLE’lilerde daha düşük olduğu gözlendi (p=0.022). Trombositopenisi olan SLE’lilerde C3a des-arg düzeyleri trombositopenisi olmayan SLE’lilere göre anlamlı yüksek bulundu (p=0.043). CXCL-10 düzeyleri; SLEDAI skoru (r=0.33, p=0.014), hastalık süresi (r=0.26, p=0.05) ve BAFF düzeyleri ile (r=0.59, p<0.001) korele bulundu. Çalışmamız sonuçları sistemik lupus eritematozus patogenezinde tip 1 interferon ve kompleman aktivasyonunun rolünü destekler niteliktedir. CXCL12, CXCL-10, C3a des-arg, LL-37 ve complement fragments Bb; sistemik lupus eritematozusta birer biomarker olarak kullanılabilir. Aynı zamanda bu parametreler belirli hasta alt gruplarının tanımlanmasında yararlı olabilir.
abstract
The complement system plays an important role in systemic lupus erythematosus and it might be a therapeutic target. Type I interferon response and type I interferon-induced gene expression are enhanced in systemic lupus erythematosus. Therefore, it was suggested that type I interferon response played a role in systemic lupus erythematosus pathogenesis. We evaluated some biomarkers associated with type I interferon response and complement activation in systemic lupus erythematsus and determined their relationship with clinical findings. We included 94 systemic lupus erythematosus patients (88 females, 6 males, mean age: 39 years) and 101 healthy controls (87 females, 14 males, mean age: 38 years). Systemic lupus erythematosus patients’ clinical and laboratory data were obtained from medical records. Complement factor H, complement fragments Bb, C3a des-arg, ficolin-2, CXCL-12 (plasma stromal cell derived factor, SDF-1), CXCL-10 (IP-10), neutrophil activation-related LL-37, and BAFF levels were determined with ELISA. Systemic lupus erythematosus patients had significantly higher CXCL-12 (p=0.001), CXCL-10 (p=0.012), and complement fragments Bb (4.36±2.2 vs 3.68±2.5, p=0.046) levels than healthy controls. C3a des-arg (p=0.003) and LL-37 (p<0.001) levels were significantly lower in systemic lupus erythematosus group when compared to controls. Ficolin-2 and BAFF levels were similar in both groups. When systemic lupus erythematosus patients whose SLEDAI scores were active and inactive were compared, it was seen that CXCL-10 was significantly higher in the former group (p=0.023). Systemic lupus erythematosus patients with arthritis had significantly higher CXCL-12 (p=0.003), BAFF (p=0.03), CXCL-10 (p=0.001) and complement fragments Bb (p=0.004) levels than systemic lupus erythematosus patients without arthritis. Systemic lupus erythematosus patients with neurologic involvement had significantly lower C3a des-arg level when compared to other systemic lupus erythematosus patients (p=0.022). C3a des-arg level was significantly higher in systemic lupus erythematosus patients with thrombocytopenia than systemic lupus erythematosus patients without thrombocytopenia (p=0.043). CXCL-10 correlated with SLEDAI score (r=0.33, p=0.014), disease duration (r=0.26, p=0.05), and BAFF level (r=0.59, p<0.001). BAFF was found to correlate with LL-37 (r=0.27, p=0.033) and disease duration (r=0.39, p=0.002). Complement fragment Bb correlated with CRP level (r=0.3, p=0.005).Our results support the roles of type I interferon response and complement activation in the pathogenesis of systemic lupus erythematosus. CXCL12, CXCL-10, C3a des-arg, LL-37, and complement fragments Bb might be used as biomarkers in systemic lupus erythematosus. They might be useful to define certain clinical subgroups.
abstract
The complement system plays an important role in systemic lupus erythematosus and it might be a therapeutic target. Type I interferon response and type I interferon-induced gene expression are enhanced in systemic lupus erythematosus. Therefore, it was suggested that type I interferon response played a role in systemic lupus erythematosus pathogenesis. We evaluated some biomarkers associated with type I interferon response and complement activation in systemic lupus erythematsus and determined their relationship with clinical findings. We included 94 systemic lupus erythematosus patients (88 females, 6 males, mean age: 39 years) and 101 healthy controls (87 females, 14 males, mean age: 38 years). Systemic lupus erythematosus patients’ clinical and laboratory data were obtained from medical records. Complement factor H, complement fragments Bb, C3a des-arg, ficolin-2, CXCL-12 (plasma stromal cell derived factor, SDF-1), CXCL-10 (IP-10), neutrophil activation-related LL-37, and BAFF levels were determined with ELISA. Systemic lupus erythematosus patients had significantly higher CXCL-12 (p=0.001), CXCL-10 (p=0.012), and complement fragments Bb (4.36±2.2 vs 3.68±2.5, p=0.046) levels than healthy controls. C3a des-arg (p=0.003) and LL-37 (p<0.001) levels were significantly lower in systemic lupus erythematosus group when compared to controls. Ficolin-2 and BAFF levels were similar in both groups. When systemic lupus erythematosus patients whose SLEDAI scores were active and inactive were compared, it was seen that CXCL-10 was significantly higher in the former group (p=0.023). Systemic lupus erythematosus patients with arthritis had significantly higher CXCL-12 (p=0.003), BAFF (p=0.03), CXCL-10 (p=0.001) and complement fragments Bb (p=0.004) levels than systemic lupus erythematosus patients without arthritis. Systemic lupus erythematosus patients with neurologic involvement had significantly lower C3a des-arg level when compared to other systemic lupus erythematosus patients (p=0.022). C3a des-arg level was significantly higher in systemic lupus erythematosus patients with thrombocytopenia than systemic lupus erythematosus patients without thrombocytopenia (p=0.043). CXCL-10 correlated with SLEDAI score (r=0.33, p=0.014), disease duration (r=0.26, p=0.05), and BAFF level (r=0.59, p<0.001). BAFF was found to correlate with LL-37 (r=0.27, p=0.033) and disease duration (r=0.39, p=0.002). Complement fragment Bb correlated with CRP level (r=0.3, p=0.005).Our results support the roles of type I interferon response and complement activation in the pathogenesis of systemic lupus erythematosus. CXCL12, CXCL-10, C3a des-arg, LL-37, and complement fragments Bb might be used as biomarkers in systemic lupus erythematosus. They might be useful to define certain clinical subgroups.
Açıklama
Tıpta Uzmanlık Tezi
Anahtar Kelimeler
Tip 1 İnterferon, Kompleman Sistemi, Sistemik Lupus Eritematozus, Systemic Lupus Erythematosus, Type 1 Interferon, Complement System
