SARS-CoV-2 infection and increasing autoimmune disorders among ICU-hospitalized COVID-19 patients.

INTRODUCTION: In acute conditions, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes multi-organ damage due to the induction of inappropriate immune responses, particularly lung tissue fibrosis. To evaluate the consequence of the deterioration of the immune system, autoimmune markers were assessed. METHODS: In a case-control study, 108 patients with coronavirus disease 2019 (COVID-19) were admitted to the intensive care unit (ICU), and 158 outpatients with mild clinical symptoms, with SARS-CoV-2 reverse transcription quantitative polymerase chain reaction (RT-qPCR) positive tests, were included for comparison. The demographic and hematologic variables and presence of the main autoantibodies in sera of 40 eligible ICU-hospitalized COVID-19 patients and 40 COVID-19 outpatients were assessed. Out of 108 COVID-19 ICU-hospitalized patients, 40 were selected as the control group (40/158) who had no underlying diseases before hospitalization, according to their self-declaration and clinical records at the time of admission. RESULTS: The results demonstrated that the main complete blood count indices, such as red blood cells and platelets, decreased dramatically in ICU-hospitalized patients. Furthermore, the autoantibody profiles were positive in 45% and 15% of ICU-admitted patients for antinuclear antibodies and antineutrophilic cytoplasmic autoantibodies, respectively. In ICU patients, anti-PM/Scl 100 or AMA-M2 was 33%. Anti SS-A, anti-SS-B, anti-Ro-52, and anti-Jo-1 in 11.5% for each one were reactive. Other autoantibodies of the ICU group were as follows: CENP (5.6%), Rib-protein (5.6%), and nucleosome (5.6%). However, only two individuals in the control group had positive results for SS-A and SS-B (5%). CONCLUSION: Induction of such particular autoantibodies by the virus can justify the multi-organ involvement and severity of the disease in ICU patients, which may also cause other organ involvement in the long term.

Gene Expression Study of Host and Mycobacterium tuberculosis Interactions in the Manifestation of Acute Tuberculosis.

Mycobacterium tuberculosis (M.tb) could induce type IV hypersensitivity. The chemotaxis of the leukocytes toward the site of infection and producing matrix metalloproteinases (MMPs) are key factors in the immune pathogenesis of tuberculosis (TB). Mononuclear cells were isolated from bronchoalveolar lavage (BAL) specimens, and the target from genomic DNA was used for qPCR TB diagnosis and cDNA for specific RT-qPCR gene expression. The subjects were then classified into TB+ and TB- groups, and the expression levels of CFP-10, ESAT-6, CCR1, CCR12 and MMP3,9 were evaluated. The mean level of CCR1 expression in TB+ and TB- patients' BAL was 1.71 ± 0.78 and 0.5 ± 0.22, respectively, which was statistically different (p = 0.01). The CCR2 level, in TB+ (2.07 ± 1.4), was higher than in TB- patients (1.42 ± 0.89, p = 0.01). The MMP9 expression in TB+ was 2.56 ± 0.68, also higher than in TB- patients (1.13 ± 0.35), while MMP3 was lower in TB+ (0.22 ± 0.09) than in TB- (0.64 ± 0.230, p = 0.05). The CCR2/CCR1 and MMP3/MMP9 balance in TB+ were reduced, compared to the TB-. The CFP-10 and ESAT-6 were highly expressed in TB+ patients. The CFP-10 expression had a strong negative correlation with albumin (r = - 0.93, p = 0.001), and a negative correlation with neutrophil (r = - 0.444, p = 0.1 with 90% CI). The MMP-9 expression showed a positive correlation with WBC count (r = 0.61, p = 0.02), in TB+, and had a negative correlation with BMI (r = 0.59, p = 0.02) in TB-. The M.tb CFP-10 might be implicated in lowering CCR2 and MMP3 expression in favour of M.tb dissemination. Moreover, the balance of CCR2/CCR1 and MMP3/MMP9 can be used as prognostic factors in the severity of TB.

Evaluation of the immunoregulatory effect of Dicrocoelium dendriticum eggs on inflammatory and anti-inflammatory cytokines in EAE model.

Experimental autoimmune encephalomyelitis (EAE) is an appropriate model for the study of the immunologic and pathologic mechanisms in multiple sclerosis (MS). According to the hygiene hypothesis, helminths can improve immunoregulation and have therapeutic effects on immune-mediated diseases. In this study, we used Dicrocoelium dendriticum (Dicrocoeliidae, Platyhelminthes) eggs for the evaluation of their prophylactic and treatment effects on EAE disease. D. dendriticum eggs were extracted. Female C57BL/6 mice were immunized with the specific antigen MOG35-55 , and then the egg extracts were utilized for prophylaxis and/or treatment. Clinical symptoms and other relevant parameters were assessed daily. The mRNA expression of transforming growth factor-ß (TGF-ß), interleukin-10 (IL-10), IL-6, IL-23 and IL-17 were assessed with a real-time polymerase chain reaction technique. Furthermore, secretion of TGF-ß and IL-17 cytokines were determined by enzyme-linked immunosorbent assay. Data indicated that clinical symptoms in prophylaxis and treatment groups were decreased significantly in comparison with the untreated control group (p < .001). Our results showed a significant decrease in IL-17, as well as an increase in TGF-ß cytokine in the treatment group compared to the EAE control group (p < .01). Furthermore, in the prophylaxis and treatment groups, the mRNA expression of disease-associated cytokines decreased and the mRNA expression of the anti-inflammatory cytokines increased. In this study, the D. dendriticum egg ameliorates the clinical symptoms of the EAE model through the modulation of related cytokines of Th17 and Treg cells. Therefore, using this parasite egg could be a new treatment for MS.

Dicrocoelium ova can block the induction phase of experimental autoimmune encephalomyelitis.

AIMS: This study aimed at investigating the impact of Dicrocoelium ova on experimental autoimmune encephalomyelitis (EAE) treatment in C57BL6 mice. METHODS AND RESULTS: Twenty-eight C57BL/6 mice were assigned into four groups as PBS, prophylaxis (P), treatment1 (T1) and treatment2 (T2). Prior to induction of EAE in prophylaxis group and on days 7 and 18 in T1 and T2 groups, respectively, Dicrocoelium eggs were injected intraperitoneally to each mouse. The clinical score, weight changes and incidence time of EAE were recorded. IFN-γ and IL-4 expression is quantified on spleen cells. Also, histopathological study by (H&E) and Toluidine-Blue (TB), and Luxol Fast Blue (LFB) were performed. The data were analysed using SPSS version 21. Mean disease scores were significantly lower in P and T1 groups than the PBS group (P = .01). IFN-γ was lower in P and T1 groups than the PBS group. The highest level of IL-4 was observed in T1 group. The total number of neuroglia cells of corpus callosum was similar in all groups, but the density increased in T1 group compared to the PBS group (P = .03). CONCLUSIONS: Dicrocoelium eggs have a great potential to stimulate immunomodulation towards treatment of EAE during the initial phase.