Toward finding the difference between untreated celiac disease and COVID-19 infected patients in terms of CD4, CD25 (IL-2 Rα), FOXP3 and IL-6 expressions as genes affecting immune homeostasis

Abstract

Background Coronavirus disease 2019 (COVID-19) is defined as an emerging infectious disease caused by severe acute respiratory syndrome coronavirus 2 and celiac disease (CD) is one of the autoimmune multiorgan diseases, which can be accompanied by an increased risk of viral infections. CD patients, especially untreated subjects, may be at greater risk of infections such as viral illnesses. Interleukin (IL)-6, CD4, CD25, and FOXP3 are known as genes affecting immune homeostasis and relate to the inflammation state. This study aimed to compare the expression levels of aforementioned genes in peripheral blood samples of CD and severe COVID-19 patients. Methods Sixty newly diagnosed CD patients with median age (mean ± SD) of 35.40 ± 24.12 years; thirty confirmed severe COVID-19 patients with median age (mean ± SD) of 59.67 ± 17.22, and 60 healthy subjects with median age (mean ± SD) of 35.6 ± 13.02 years; were recruited from March to September 2020. Fresh whole blood samples were collected, total RNA was obtained and cDNA synthesis was carried out. RNA expression levels of IL-6, CD4, CD25, and FOXP3 genes were assessed using real-time quantitative RT-PCR according to the 2−∆∆Ct formula. Statistical analysis was performed using SPSS (V.21) and GraphPad, Prism (V.6). Results While increased expression of CD4, CD25, and FOXP3 was observed in CD patients compared to the control group (p = 0.02, p = 0.03, and p < 0.0001 respectively) and COVID-19 patients group (p < 0.0001 for all of them), their expression levels in COVID-19 patients decreased compared to controls (p < 0.0001, p = 0.01, p = 0.007, respectively). Increased IL-6 expression was observed in both groups of patients compared to controls (p < 0.0001 for both of them). Conclusions Although untreated CD patients may be at greater risk of developing into severe COVID-19 if they are infected by SARS-CoV-2 virus (due to their high expression of IL-6), increased expression of anti-inflammatory markers in these patients may be beneficial for them with the ability of reducing the severity of COVID-19 disease, which needs to be proven in future studies involving celiac patients infected with COVID-19.

Celiac Disease and Targeting the Molecular Mechanisms of Autoimmunity in COVID Pandemic

“…People with CD, mainly untreated patients, may be at higher risk for infections such as COVID-19 [ 98 , 161 ].…”

“…In the recently published study by Asri et al, it is suggested that high levels of IL-6 may predispose non-dietary CD patients to severe complications if infected with SARS-CoV-2. In this case, improved expression of CD4, CD25 and FOXP3 as anti-inflammatory markers may be helpful in reducing the serious adverse events of SARS-CoV-2 infection, as demonstrated in the final conclusions of this clinical trial with the control group [ 98 , 179 ].…”

“…However, a higher expression of IL-6 was observed in both groups of patients compared to controls. Authors concluded that due to the high expression of IL-6, patients with untreated CD may be at higher risk of developing severe COVID-19, but the increased expression of anti-inflammatory markers may be salutary for them, possible through diminishing the gravity of COVID-19, aspects to be scientifically proved in time to come research on CD patients contaminated with SARS-CoV-2 [ 98 ].…”

SARS-CoV-2 Spike Protein-Activated Dendritic Cell-Derived Extracellular Vesicles Induce Antiviral Immunity in Mice

“…Several studies indicated that IL-6 plays an important role in Tfh cell differentiation, and the production of IL-6 by different T-cell types after SARS-CoV-2 infection is beneficial for resolving the viral infection. , As shown in Figure C, at day 7, IL-6 was not elevated in the serum of mice for all groups. However, on day 15, the IL-6 level was significantly elevated in the serum obtained from mice treated with DEVs (Figure C) (DEVs vs DCs or Spike at day 15, p ≤ 0.005, n = 3).…”

“…44,45 Interestingly, optimum production of IL-6 and other proinflammatory markers by various cell types after SARS-CoV-2 infection provided a positive indication in resolving the viral infection. 21 It is important to note that although DEVs induce antibodies at early time points, however, the antibody level becomes equivalent at later stages, as observed with DCs and Spike. A similar observation was also correlated with the ability to neutralize the virus in an in vitro model.…”