The Effect of Exposure to SARS-CoV-2 Vaccination and Infection on Humoral and Cellular Immunity in a Cohort of Patients with Immune-Mediated Diseases: A Pilot Study.

Immunization against COVID-19 is needed in patients with immune-mediated inflammatory diseases (IMIDs). However, data on long-term immunity kinetics remain scarce. This study aimed to compare the humoral and cellular response to COVID-19 in patients with immune-mediated inflammatory diseases (IMIDs) compared to healthy controls. We compared the humoral and cellular response to SARS-Cov-2 elicited by vaccination and/or infection in a prospective cohort of 20 IMID patients compared with a group of 21 healthcare workers (HCWs). We assessed immunity before and after the third and fourth dose of BNT162b2 or after COVID-19 infection using quantitative IgG anti-SARS-CoV-2 Spike antibody (anti-S-IgG), neutralization assay, and specific interferon-gamma (IFN-g) release assay (IGRA). The responses were compared with those of healthy controls. The two groups were similar in age and total exposure, becoming infected for the first time, mainly after the third dose. Neutralizing antibodies and IGRA were negative in 9.5% of IMID patients but not in any HCWs. No significant difference was found between neutralization titers to BA.1 in the IMID and the HCW groups. The study highlights the SARS-CoV-2 immunological responses in healthy controls and IMID patients, suggesting that the combined stimuli of vaccination and infection in IMID patients could promote a more profound immunological response.

Prevalence of Apical Periodontitis in Patients with Autoimmune Liver Diseases on Immune Suppressants and Immune Modulators: A Cross-sectional Study.

INTRODUCTION: Autoimmune liver diseases (ALDs) are chronic conditions generated by an immune-mediated autoaggressive inflammatory reaction in genetically susceptible individuals. The purpose of this study was to evaluate the prevalence of apical periodontitis (AP) in patients suffering from ALDs undergoing treatment with the immune suppressants glucocorticoids, azathioprine, and/or ursodeoxycholic acid. METHODS: The ALD group included 46 patients (11 men and 35 women, average age = 57.9 ± 11.8 years) and 1186 teeth. The control group included 50 healthy patients not taking any medications (15 men and 35 women, average age = 58.6 ± 10.4 years) and 1251 teeth. Demographic data and medical, pharmacologic, and dental history were recorded. Dental and radiographic examinations were performed. The presence of AP; the periapical index score; decayed, missing, and filled teeth; quality of restoration, and root canal treatment were evaluated. The influence of the medications the patients were taking on the prevalence of AP was also tested. RESULTS: The prevalence of AP was significantly lower in ALDs than in the control group at the patient (P = .019) and tooth level (P = .014). Smoking and age were associated with a significant increase in AP in cases and controls (P = .045 and P = .001, respectively). In both groups, endodontically treated teeth showed a higher prevalence of AP. CONCLUSIONS: Considering the limitations because of the observational nature of the study, the patients affected by ALDs liver diseases and undergoing treatment with immune suppressors (often associated with immune modulators) were found to exhibit a lower prevalence of AP.

A review of the main genetic factors influencing the course of COVID-19 in Sardinia: the role of human leukocyte antigen-G.

Introduction: A large number of risk and protective factors have been identified during the SARS-CoV-2 pandemic which may influence the outcome of COVID-19. Among these, recent studies have explored the role of HLA-G molecules and their immunomodulatory effects in COVID-19, but there are very few reports exploring the genetic basis of these manifestations. The present study aims to investigate how host genetic factors, including HLA-G gene polymorphisms and sHLA-G, can affect SARS-CoV-2 infection. Materials and Methods: We compared the immune-genetic and phenotypic characteristics between COVID-19 patients (n = 381) with varying degrees of severity of the disease and 420 healthy controls from Sardinia (Italy). Results: HLA-G locus analysis showed that the extended haplotype HLA-G*01:01:01:01/UTR-1 was more prevalent in both COVID-19 patients and controls. In particular, this extended haplotype was more common among patients with mild symptoms than those with severe symptoms [22.7% vs 15.7%, OR = 0.634 (95% CI 0.440 - 0.913); P = 0.016]. Furthermore, the most significant HLA-G 3'UTR polymorphism (rs371194629) shows that the HLA-G 3'UTR Del/Del genotype frequency decreases gradually from 27.6% in paucisymptomatic patients to 15.9% in patients with severe symptoms (X2 = 7.095, P = 0.029), reaching the lowest frequency (7.0%) in ICU patients (X2 = 11.257, P = 0.004). However, no significant differences were observed for the soluble HLA-G levels in patients and controls. Finally, we showed that SARS-CoV-2 infection in the Sardinian population is also influenced by other genetic factors such as ß-thalassemia trait (rs11549407C>T in the HBB gene), KIR2DS2/HLA-C C1+ group combination and the HLA-B*58:01, C*07:01, DRB1*03:01 haplotype which exert a protective effect [P = 0.005, P = 0.001 and P = 0.026 respectively]. Conversely, the Neanderthal LZTFL1 gene variant (rs35044562A>G) shows a detrimental consequence on the disease course [P = 0.001]. However, by using a logistic regression model, HLA-G 3'UTR Del/Del genotype was independent from the other significant variables [ORM = 0.4 (95% CI 0.2 - 0.7), PM = 6.5 x 10-4]. Conclusion: Our results reveal novel genetic variants which could potentially serve as biomarkers for disease prognosis and treatment, highlighting the importance of considering genetic factors in the management of COVID-19 patients.

The double-sided of human leukocyte antigen-G molecules in type 1 autoimmune hepatitis.

The immunomodulatory effects of HLA-G expression and its role in cancers, human liver infections and liver transplantation are well documented, but so far, there are only a few reports addressing autoimmune liver diseases, particularly autoimmune hepatitis (AIH). Method and materials: We analyzed the genetic and phenotypic characteristics of HLA-G in 205 type 1 AIH patients (AIH-1) and a population of 210 healthy controls from Sardinia (Italy). Results: Analysis of the HLA-G locus showed no substantial differences in allele frequencies between patients and the healthy control population. The HLA-G UTR-1 haplotype was the most prevalent in both AIH-1 patients and controls (40.24% and 34.29%). Strong linkage was found between the HLA-G UTR-1 haplotype and HLA-DRB1*03:01 in AIH-1 patients but not controls (D' = 0.92 vs D' = 0.50 respectively; P = 1.3x10-8). Soluble HLA-G (sHLA-G) levels were significantly lower in AIH-1 patients compared to controls [13.9 (11.6 - 17.4) U/mL vs 21.3 (16.5 - 27.8) U/mL; P = 0.011]. Twenty-four patients with mild or moderate inflammatory involvement, as assessed from liver biopsy, showed much higher sHLA-G levels compared to the 28 patients with severe liver inflammation [33.5 (23.6 - 44.8) U/mL vs 8.8 (6.1 - 14.5) U/mL; P = 0.003]. Finally, immunohistochemistry analysis of 52 liver biopsies from AIH-1 patients did not show expression of HLA-G molecules in the liver parenchyma. However, a percentage of 69.2% (36/52) revealed widespread expression of HLA-G both in the cytoplasm and the membrane of plasma cells labeled with anti-HLA-G monoclonal antibodies. Conclusion: This study highlights the positive immunomodulatory effect of HLA-G molecules on the clinical course of AIH-1 and how this improvement closely correlates with plasma levels of sHLA-G. However, our results open the debate on the ambiguous role of HLA-G molecules expressed by plasma cells, which are pathognomonic features of AIH-1.

Evaluation of antibody response to BNT162b2 mRNA COVID-19 vaccine in patients affected by immune-mediated inflammatory diseases up to 5 months after vaccination.

SARS-CoV-2 vaccination with mRNA product BNT162b2 elicited high immunogenicity in healthy subjects in trials. This study aims to better understand the factors that influence the humoral immune response to vaccination against SARS-CoV-2 in patients with immune-mediated inflammatory diseases (IMIDs). We enrolled patients and healthy healthcare workers control group (HCW) that underwent mRNA BNT162b2 vaccination and measured the serum IgG anti-S-RBD response at booster dose (T1), one month after booster dose (T2) and up to 5 months (T3). Demographic, disease-specific and vaccination data were recorded. Vaccination response of 551 participants naïve to SARS-CoV-2 infection were included in HCW and 102 in the IMID group, analyzing separately those on anti-CD20. At T2 all naïve HCW developed anti-S-RBD-IgG, while 94% of IMID responded (p < 0.001). IMID patients had a significantly different level of IgG than HCW at both T1 (p = 0.031), T2 (p < 0.001), while there was no significant difference at T3. There were no statistically significant differences according to the IMID type or to ongoing treatment with immunosuppressants, corticosteroids or biological drugs other than anti-CD20. The proportion and magnitude of response was significantly lower in IMID treated with anti-CD20 drugs. There was a correlation with age at T1 and at T2 but not at T3, stronger in patients than in HCW. Immune response close after BNT162b2 vaccination is reduced in patients with IMID, but there is no significant difference at 5 months. The measured reduction is related to age and the disease itself rather than treatments, with the exception of anti-CD20 drugs.