Clinical Immunology Communications最新文献

Emerging research shows that innate immunity can also keep the memory of prior experiences, challenging the long-held notion that immunological memory is only the domain of the adaptive immune cells. However, the absence of immunological memory in innate immune responses has recently been brought into question. Now it is known that after a few transient activations, innate immune cells may acquire immunological memory phenotype, resulting in a stronger response to a subsequent secondary challenge. When exposed to particular microbial and/or inflammatory stimuli, trained innate immunity is characterized by the enhanced non-specific response, which is regulated by substantial metabolic alterations and epigenetic reprogramming. Trained immunity is acquired by two main reprogramming, namely, epigenetic reprogramming and metabolic adaptation/reprogramming. Epigenetic reprogramming causes changes in gene expression and cell physiology, resulting in internal cell signaling and/or accelerated and amplified cytokine release. Metabolic changes due to trained immunity induce accelerated glycolysis and glutaminolysis. As a result, trained immunity can have unfavorable outcomes, such as hyper inflammation and the development of cardiovascular diseases, autoinflammatory diseases, and neuroinflammation. In this review, the current scenario in the area of trained innate immunity, its mechanisms, and its involvement in immunological disorders are briefly outlined.

Aim

Serum calprotectin (SC), a novel biomarker of inflammatory bowel diseases (IBD), has been recently investigated with conflicting results. The purpose of this study was to assess the ability of SC to predict relapse in IBD patients treated by biologic therapies, and to evaluate the correlation between SC, clinical and endoscopic relapse and other biomarkers as fecal calprotectin (FC) and C-reactive protein (CRP).

Methods

All consecutive IBD patients in deep remission (clinical, endoscopic or imaging remission) were followed 12 months in this prospective study. Blood and stool samples were collected for SC, serum CRP and FC. SC was measured the day of inclusion (baseline, D0), 3 months (M3) and at 6 months (M6) or during the study period for clinical relapse. Relapse was defined as clinical, biomarkers, or endoscopic/imaging activities. Evolution of SC was quantified before relapse to analyze a predicting value of loss of response (LOR). SC for patients with active IBD and those with symptoms without inflammation were also compared.

Results

Among the 119 patients included, 54 (46.4%) patients experienced a disease relapse during follow-up. Median SC levels did not increase in patients with clinical relapse (3.15 µg/ml at baseline, 3.38 µg/ml at M3, 3.33 µg/ml at M6 and 3.99 µg/ml in case of relapse (p = 0.63)). SC were compared during relapse in patients with endoscopic remission but clinical symptoms defined as secondary Irritable Bowel Syndrome (IBS). SC levels were higher in active IBD and similar between the groups of patients with IBS or deep remission (3.05 µg/ml IBS vs 2.99 µg/ml remission vs 5.1 µg/ml for clinical relapse, p = 0.04). In patients with clinical symptoms, SC presents a good predictive value for relapse (AUROC 0.764, IC95: 0.68–0.88), with a sensitivity of 72%, a specificity of 77%, using a cut-off value of 4.45 µg/ml. A weak, but significant correlation was found between SC and FC levels (r = 0.35, P = 0.001). A combined score with CRP, FC and SC is not efficient to improve IBD diagnostic.

Conclusion

SC was significantly higher in patients with clinical relapse compared to those with endoscopic remission with or without clinical symptoms. SC allow to discriminate patients with active IBD or with IBS but failed to predict relapse.

SARS-CoV-2 causes Coronavirus Disease 2019 (COVID-19), an infectious condition that can present none or one or more of these symptoms: fever, cough, headache, sore throat, loss of taste and smell, aches, fatigue and musculoskeletal pain. For the prevention of COVID-19, there are vaccines available including those developed by Pfizer, Moderna, Sinovac, Janssen, and AstraZeneca. Recent evidence has shown that some COVID-19-vaccinated individuals can occasionally develop as a potential side effect Guillain-Barre syndrome (GBS), a severe neurological autoimmune condition in which the immune response against the peripheral nerve system (PNS) can result in significant morbidity. GBS had been linked previously to several viral or bacterial infections, and the finding of GBS after vaccination with certain COVID-19, while rare, should alert medical practitioners for an early diagnosis and targeted treatment. Here we review five cases of GBS that developed in different countries after COVID-19 vaccination.

Generating memory T cell responses besides humoral immune responses is essential when it comes to the efficacy of a vaccine. In this study, the presence of memory T cell responses after aluminum-adjuvanted inactivated whole-virion SARS-CoV-2 vaccine (CoronaVac) in seronegative and seropositive elderly individuals were examined. CD4⁺ and CD8⁺ memory T cell proliferation and IFN-γ production capacities were evaluated. Additionally, clinical frailty scale (CFS) and FRAIL scales of the individuals were scored. CD4⁺ memory T cell responses more prominent than CD8⁺ memory T cells. In seronegative individuals, 80% of them had memory CD4⁺ and IFN-γ, whereas 50% of them had memory CD4⁺ and all of them had IFN-γ responses. Additionally, 40% of seronegative patients and 50% of seropositive patients had memory CD8⁺ responses. To sum up, humoral immune responses are not associated with memory T cell responses, and in seronegative individuals, memory T cell responses can be detected.

Adalimumab is a fully-humanized monoclonal antibody against tumor necrosis factor alpha (TNF-α) that is used to suppress the immune response. Though rare, hypersensitivity reactions to adalimumab can occur. Desensitization protocols have been developed to safely administer many medications in patients with Type I and Type IV hypersensitivity reactions. This case describes a teenage patient with Crohn's Disease who developed a delayed pruritic urticarial rash hypersensitivity reaction to adalimumab. A novel desensitization protocol was developed based on available literature. Our protocol consisted of four weekly doses, with the first dose in seven steps, second dose in two steps, and two full doses at weekly intervals, before spacing to biweekly injections. This multipart protocol was necessary due to the long half-life of adalimumab, which also allows for maintenance of the desensitized state in between injections. This protocol successfully treated our patient's hypersensitivity to adalimumab, with no further hypersensitivity occurring over a two-year follow-up period.

Vitiligo is an autoimmune disorder, which is characterized by the chronic loss of melanocytes and subsequent lack of melanin from the skin or hair or both. The resultant depigmentation state of the skin causing irregular white patches deteriorates the vitiligo patients’ quality of life by major stigmatizing psychological impact. Despite tremendous studies for the past several decades, there has been a dearth of precise theranostics for vitiligo, which necessitates to revisit the molecular changes in vitiligo. Following advent of omics research, the examination of circulating non-coding RNAs including miRNAs has been enormously utilized for potential vitiligo therapeutic targets, however the expression profile of miRNAs and their target genes have not been studied at exosomal level in correlation with the differentially expressed genes (DEG) at the tissue level in vitiligo patients.

Exosomes are tiny extracellular vesicles, with diameter approximately 30–200 nm, which is released from various cell types, and found in different biofluids including blood serum and plasma. Notably, the exosomes have been found to mimic the constituents of their parent cells, enabling it an excellent theranostics platform for diseased condition. Therefore, we investigated the plasma exosomal miRNA and identified the target genes associated with immune infiltration in vitiligo patients compared to healthy subjects. In this study, 65 DEGs have been analyzed by heatmap, among which 44 genes are up-regulated and 21 are down-regulated, which are associated with melanin- biosynthetic and metabolic process. CENPN and SLIRP were found to be substantially correlated with immune cells viz. CD8+ T cells, M1-macrophage. Among several target genes by the exosomal miRNAs, SLIRP has been found to be associated with miR-16-5p, whereas CENPN has been found to be associated with miR-6721-5p, and miR-486-5p. Conclusively, the exosomal miR-16-5p, miR-6721-5p, and miR-486-5p could be potential theranostics targets for vitiligo.

Pre-existing SARS-CoV-2-specific T cells, but not antibodies, have been detected in some unexposed individuals. This may account for some of the diversity in clinical outcomes ranging from asymptomatic infection to severe COVID-19. Although age is a risk factor for COVID-19, how age affects SARS-CoV-2-specific T cell responses remains unknown. We found that pre-existing T cell responses to specific SARS-CoV-2 proteins, Spike (S) and Nucleoprotein (N), were significantly lower in elderly donors (>70 years old) than in young donors. However, substantial pre-existing T cell responses to the viral membrane (M) protein were detected in both young and elderly donors. In contrast, young and elderly donors exhibited comparable T cell responses to S, N, and M proteins after infection with SARS-CoV-2. These data suggest that although SARS-CoV-2 infection can induce T cell responses specific to various viral antigens regardless of age, diversity of target antigen repertoire for long-lived memory T cells specific for SARS-CoV-2 may decline with age; however, memory T cell responses can be maintained by T cells reactive to specific viral proteins such as M. A better understanding of the role of pre-existing SARS-CoV-2-specific T cells that are less susceptible to age-related loss may contribute to development of more effective vaccines for elderly people.

In Pakistan, the Hepatitis E virus (HEV) is prevalent. HEV exposure is deadly during pregnancy, with high infection rates in both the mother and the baby, even in asymptomatic situations. The researcher examined HEV-negative pregnant women with acute hepatitis or increased renal characteristic assessments at 12 medical sites in Khyber Pakhtunkhwa, Pakistan, to identify maternal and fetal disease risks from August to December 2018. Except for one during the entire pregnancy, twenty-five of the 135 females were HEV-free and in the perinatal period. HEV infection was found in 0.19% of newly pregnant women. Also, 11 cases of forcible induction of labor, 7 cases of normal labor, 5 cases of normal labor (full-term), 2 cases of death, and 1 case of intrauterine death were reported before going to the doctor a girl had an abortion. There were eight postpartum deaths: five from infections, four from miscarriages, and two from miscarriages. While 18 mothers who survived voluntarily or intentionally induced abortions and three women who continued to get pregnant but did not deliver died as a result of abortion. The current study found that HEV infection during pregnancy raised the death rate by 14.2%.

Paroxysmal nocturnal hemoglobinuria (PNH) is a non-malignant clonal disorder of the pluripotent hematopoietic stem cell. Currently, Eculizumab, Ravulizumab, and Pegcetacoplan are the approved drugs to treat PNH. In order to assess the efficacy and safety of different medications available for PNH, we performed a systematic search. The primary efficacy endpoint was the percentage change in lactate dehydrogenase, transfusion avoidance, and stabilized hemoglobin. Key secondary endpoints included the proportion of patients with breakthrough hemolysis, anemia, adverse events, number of deaths, and discontinuation of treatment. From 2526 articles retrieved from electronic databases and manual searches, a total of five studies were included in this review: 1 observational study and 4 randomized clinical trials. For all efficacy and safety endpoints, Ravulizumab and Pegcetacoplan achieved noninferiority compared with the first standardized treatment Eculizumab. The use of complement inhibition therapy can further improve hematological outcomes in PNH patients.

Imprinting of the specific molecular image of a given protein antigen into immunological memory is one of the hallmarks of immunity. A later contact with a related, but different antigen should not trigger the memory response (because the produced antibodies would not be effective). The preferential expansion of cross-reactive antibodies, or T-lymphocytes for that matter, by a related antigen has been termed the original antigenic sin and was first described by Thomas Francis Jr. in 1960. The phenomenon was initially described for influenza virus, but also has been found for dengue and rotavirus. The antibody dependent enhancement observed in feline coronavirus vaccination also may be related to the original antigenic sin. For a full interpretation of the effectivity of the immune response against SARS-CoV-2, as well as for the success of vaccination, the role of existing immunological memory against circulating corona viruses is reviewed and analyzed.