Immune Cell Response during COVID-19 Infection and following SARS-CoV-2 Vaccination in Patients Admitted to Intensive Care Unit.

Background: Immune response plays a crucial role in virus clearance during COVID-19 infection and underpins vaccine efficacy. Herein, we aimed to assess the immune response during COVID-19 infection and following SARS-CoV-2 vaccination. Methods: In this retrospective study, 94 confirmed COVID-19 patients admitted to the intensive care unit were categorized into unvaccinated patients (n = 50), including 33 deceased and 17 discharged patients, and vaccinated group (n = 44) with 26 deceased and 18 discharged patients. Records of patients with severe COVID-19 admitted to the ICU between March, 2021 and March, 2022 were gathered and analyzed. Result: The assessment of immune cell counts revealed a large rise of neutrophils associated to decrease number of lymphocytes in patients with COVID-19 infection. In dead patients, we detected a significant correlation between neutrophils and inflammatory parameters such as IL-6 and CRP. Moreover, analysis of immune cell count following vaccination did not reveal any significant difference. However, the most substantial result, herein, detected is the decrease level of IL-6 in vaccinated patients as compared to unvaccinated. The reduce level of IL-6 following vaccination is observed in discharged patients as compared to deceased. Regarding the level of mortality after vaccination, we showed that all patients who received the first dose were died (46.1%, n = 12) as compared to those who have received two doses (34.6%, n = 9) and the third dose of vaccine (19.23%, n = 3) (p=0.0018). Strikingly, studying the inflammatory parameters after each vaccine dose, we revealed a significant decrease of IL-6 level after the booster dose (third dose), especially in vaccinated discharged patients. Conclusions: Neutrophils combined with IL-6 and CRP can be very useful markers to predict disease severity in patients admitted to ICU. The decrease level of IL-6 in vaccinated group pointed out the impact of vaccination to prevent inflammatory cytokine release.

High levels of proinflammatory cytokines IL-6, IL-8, TNF-Α, IL-23, and IFN- in Tunisian patients with type 1 autoimmune hepatitis.

Autoimmune hepatitis (AIH) is a chronic hepatitis of unknown etiology and several cytokines have been implicated in its pathogenesis and onset. Our objective was to determine the profile of pro and anti-inflammatory cytokines, including IL-1ß, IL-6, IL-8, IL-23, IFN-, TNF-α, IL-10 in autoimmune hepatitis and their association with HLA gene polymorphisms. Serum cytokine levels were determined in 50 autoimmune hepatitis patients and one hundred fifty controls using chemiluminescence and ELISA techniques and HLA genotyping performed by PCR SSP. The levels of IL-6 (12 pg/mL vs. 5.5 pg/mL, p = 0.017), IL-8 (24.1 pg/mL vs. 7.8 pg/mL, p = 0.006), and TNF-α (61.1 pg/mL vs. <4.00 pg/mL, p = 0.002) were significantly higher in AIH patients in pretreatment phase compared to levels after remission and in controls. HLA*DRB15 was significantly associated with higher levels of IL-8. IL-6, IL-8, and TNF-α may be biomarkers of AIH activity. HLA gene expression may play a role in higher cytokine production and could allow an earlier diagnosis and better management of the disease.

Cytotoxic T lymphocyte antigen-4 gene polymorphisms and susceptibility to type 1 autoimmune hepatitis in the Tunisian population.

Genetic factors and gene polymorphisms leading to the onset of autoimmune response in autoimmune hepatitis (AIH) are still not full elucidated. Since the CTLA-4 molecule is a key modulator of the lymphocytes responses we hypothezied that deficiencies or mutations in the gene encoding CTLA4 protein may be involved in AIH susceptibility and trigger the autoimmune response. We investigated 3 distinct polymorphic sites (+49A > G, CT60 G > A and -318C > T) of the CTLA4 gene in 50 AIH patients and 100 healthy controls using the KASP genotyping technology. A significant positive association with AIH susceptibility was found for the GG genotype in +49 position of the CTLA4 gene which was significantly higher in AIH patients compared to controls (28% vs 9%, p = 0.003, OR = 3.93 [1.56-9.88]). The CTLA4 A/A genotype in position CT60 was more significantly frequent in controls comparing to AIH patients and could be considered as a protective genotype for the tunisian patients. CTLA4 genotyping in position -318 did not show any statistically significant difference in genotype or allele distribution. The CTLA4 gene polymorphism in position +49 is associated to AIH susceptibility in the Tunisian population. Mutation in the CTLA4 gene may lead to a modification of the CTLA4 protein structure that could have functional relevance in AIH pathogenesis and onset.