Secretory IgMs (SIgMs) were amongst the first identified immunoglobulins. However, their importance was not fully understood and recent advances have shown they play a key role in establishing and ...promoting commensal gut tolerance in mice and humans. The true interactions between SIgMs and the microbiota remain controversial and we aim to consolidate current knowledge in this review. Through comprehensive examination of SIgMs and their corresponding B cell secretors in several different pathological immunological contexts, we review the presumed role of these molecules in gut tolerance, inflammatory bowel diseases, and lung immunity. As SIgMs harbor a mostly tolerogenic function, we posit that their inclusion in further immunological research is paramount.
Human secretory immunoglobulin-M (SIgM) is mostly natural IgM and shapes the colonization of mucosal surfaces.SIgMs can selectively bind commensal bacteria at mucosal surfaces and may have overlapping functions with SIgAs in healthy humans and mice.SIgM can regulate B cell development.SIgMs can promote central and mucosal tolerance, which might influence the development and outcomes of autoimmune conditions in mice and humans.The B-1 cell pool produces the bulk of natural IgM and has regulatory functions in the establishment of tolerance in mice.If robustly elicited, SIgM might be potentially beneficial in helping to treat certain pathologies such as infections or autoimmune diseases, although robust testing is still warranted.
Dihydrogen (H2) is considered nowadays as a sustainable energy carrier and exhibits a high energy density in its highly compressed state. Different countries in the world are developing industrial ...production and are scaling up water electrolysis processes with clear roadmaps. Alkaline water electrolysis is an affordable technology that avoids the use of platinum group metals with a good compromise of efficiency because of the development of new cost-effective and Earth-abundant materials of electrodes and new anion-exchange membranes. Here, we report on the use of emerging and selective laser melting (SLM) technology for the three-dimensional (3D) printing of binary alloyed NiFe, NiMo, NiCr, and NiCo electrode materials at an applied scale. These materials are preliminarily tested for hydrogen and oxygen evolution half-reactions in alkaline conditions to select the most promising combinations of cathode/anode combinations for overall water electrolysis. On the basis of three key performance metrics (KPMs, namely, overpotential values at 10 and 50 mA cm–2 and the stability in operation over 6 days at 50 mA cm–2), NiCr and NiCo are preferred for the cathode, whereas the anode is NiMo or NiFe. Moreover, to facilitate the release of the electrogenerated gas bubbles, the patterning of 3D-printed electrodes with either roughly conical holes or ramps is considered as a third experimental factor. The water electrolysis process is then fully optimized using the formalism of design of experiments (DOE), which allows to reduce the number of experiments without loss in the quality of conclusions. This study reveals that NiCo and NiMo will be preferentially used as the cathode and anode, respectively, to decrease the cell overvoltage, whereas NiFe as the anode yields the best stability in operation. Besides, the impact of the patterns printed by SLM on the KPMs is somewhat limited, even though the presence of holes is rather beneficial for decreasing cell overvoltage. Interestingly, an approximate calculation of the consumed energy for the production of 1 kg of H2 from the combination of NiCo/NiMo/holes as the cathode/anode/pattern yields 50.6 kWh/kg of H2, which is quite promising if one refers to the 48 kWh industrial target set by European Union for 2030.
Systemic and mucosal humoral immune responses are crucial to fight respiratory viral infections in the current pandemic of COVID-19 caused by the SARS-CoV-2 virus. During SARS-CoV-2 infection, the ...dynamics of systemic and mucosal antibody infections are affected by patient characteristics, such as age, sex, disease severity, or prior immunity to other human coronaviruses. Patients suffering from severe disease develop higher levels of anti-SARS-CoV-2 antibodies in serum and mucosal tissues than those with mild disease, and these antibodies are detectable for up to a year after symptom onset. In hospitalized patients, the aberrant glycosylation of anti-SARS-CoV-2 antibodies enhances inflammation-associated antibody Fc-dependent effector functions, thereby contributing to COVID-19 pathophysiology. Current vaccines elicit robust humoral immune responses, principally in the blood. However, they are less effective against new viral variants, such as Delta and Omicron. This review provides an overview of current knowledge about the humoral immune response to SARS-CoV-2, with a particular focus on the protective and pathological role of humoral immunity in COVID-19 severity. We also discuss the humoral immune response elicited by COVID-19 vaccination and protection against emerging viral variants.
The Nightmare Monitoring of JAKinhibs Paul, Stéphane; Roblin, Xavier
Gastroenterology (New York, N.Y. 1943),
September 2020, 2020-09-00, 20200901, Letnik:
159, Številka:
3
Journal Article
LINKED CONTENT
This article is linked to Rundquist et al papers. To view these articles, visit https://doi.org/10.1111/apt.16193 and https://doi.org/10.1111/apt.16241
Highlights ► To date, mucosal vaccines are poorly efficient. ► Select antigens, adjuvant and design new mucosal routes of administration. ► Induce protective immunity at mucosal surfaces. ► Mucosal ...vaccine would make immunization procedures easier for mass administration.
Abstract
Despite huge advances in understanding the molecular basis of IBD, clinical management has continued to rely on a “trial and error” approach. In addition, a therapeutic ceiling has emerged ...whereby even the most effective interventions are only beneficial for approximately 30% of patients. Consequently, several tools have been developed to aid stratification and guide treatment-decisions.
We review the potential application for many of these precision medicine approaches, which are now almost within reach. We highlight the importance of early action (and avoiding inaction) to ensure the best outcomes for patients and how combining early action with precision tools will likely ensure the right treatment is delivered at the right time and place for each individual person living with IBD.
The lack of clinical impact to date from precision medicine, despite much hype and investment, should be tempered with the knowledge that clinical translation can take a long time, and many promising breakthroughs might be ready for clinical implementation in the near future. We discuss some of the remaining challenges and barriers to overcome for clinical adoption. We also highlight that early recognition, early diagnosis, early stratification, and early intervention go hand in hand with precision medicine tools. It is the combination of these approaches that offer the greatest opportunity to finally deliver on the promise of precision medicine in IBD.
Lay Summary
Several precision medicine tools to guide treatment decisions are almost ready for clinical implementation. We highlight that combining these tools with a focus on early action offers the greatest opportunity to finally deliver on the promise of precision medicine in IBD.
Following severe adverse reactions to the AstraZeneca ChAdOx1-S-nCoV-19 vaccine
, European health authorities recommended that patients under the age of 55 years who received one dose of ...ChAdOx1-S-nCoV-19 receive a second dose of the Pfizer BNT162b2 vaccine as a booster. However, the effectiveness and the immunogenicity of this vaccination regimen have not been formally tested. Here we show that the heterologous ChAdOx1-S-nCoV-19 and BNT162b2 combination confers better protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection than the homologous BNT162b2 and BNT162b2 combination in a real-world observational study of healthcare workers (n = 13,121). To understand the underlying mechanism, we conducted a longitudinal survey of the anti-spike immunity conferred by each vaccine combination. Both combinations induced strong anti-spike antibody responses, but sera from heterologous vaccinated individuals displayed a stronger neutralizing activity regardless of the SARS-CoV-2 variant. This enhanced neutralizing potential correlated with increased frequencies of switched and activated memory B cells that recognize the SARS-CoV-2 receptor binding domain. The ChAdOx1-S-nCoV-19 vaccine induced a weaker IgG response but a stronger T cell response than the BNT162b2 vaccine after the priming dose, which could explain the complementarity of both vaccines when used in combination. The heterologous vaccination regimen could therefore be particularly suitable for immunocompromised individuals.
LINKED CONTENT
This article is linked to Tournier et al and Demarzo et al papers. To view these articles, visit https://doi.org/10.1111/apt.16333 and https://doi.org/10.1111/apt.16494
PDF
