The association between type I interferon, response, complement activation and clinical findings in systemic lupus erythematosus

Tıpta Uzmanlık TeziSistemik 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.abstractThe 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

The Impact of CoronaVac Vaccination on 28-day Mortality Rate of Critically Ill Patients with COVID-19 in Türkiye

Background:Vaccines against coronavirus disease-19 (COVID-19) have been effective in preventing symptomatic diseases, hospitalizations, and intensive care unit (ICU) admissions. However, data regarding the effectiveness of COVID-19 vaccines in reducing mortality among critically ill patients with COVID-19 remains unclear.Aims:To determine the vaccination status and investigate the impact of the COVID-19 vaccine on the 28-day mortality in critically ill patients with COVID-19.Study Design:Multicenter prospective observational clinical study.Methods:This study was conducted in 60 hospitals with ICUs managing critically ill patients with COVID-19. Patients aged ≥ 18 years with confirmed COVID-19 who were admitted to the ICU were included. The present study had two phases. The first phase was designed as a one-day point prevalence study, and demographic and clinical findings were evaluated. In the second phase, the 28-day mortality was evaluated.Results:As of August 11, 2021, 921 patients were enrolled in the study. The mean age of the patients was 65.42 ± 16.74 years, and 48.6% (n = 448) were female. Among the critically ill patients with COVID-19, 52.6% (n = 484) were unvaccinated, 7.7% (n = 71) were incompletely vaccinated, and 39.8% (n = 366) were fully vaccinated. A subgroup analysis of 817 patients who were unvaccinated (n = 484) or who had received two doses of the CoronaVac vaccine (n = 333) was performed. The 28-day mortality rate was 56.8% (n = 275) and 57.4% (n = 191) in the unvaccinated and two-dose CoronaVac groups, respectively. The 28-day mortality was associated with age, hypertension, the number of comorbidities, type of respiratory support, and APACHE II and sequential organ failure assessment scores (p < 0.05). The odds ratio for the 28-day mortality among those who had received two doses of CoronaVac was 0.591 (95% confidence interval: 0.413-0.848) (p = 0.004).Conclusion:Vaccination with at least two doses of CoronaVac within six months significantly decreased mortality in vaccinated patients than in unvaccinated patients