Water molecule elimination from the protonated methanol dimer ion-An example of a size-selective intracluster reaction.

The abundance of extraterrestrial methanol makes the reaction between methanol molecules in a molecular cluster a possible key step in the search for mechanisms for the formation of more complex molecules under the conditions of the interstellar medium as well as circumstellar and planetary atmospheres. The reaction leading to the formation of the dimethyl ether ion from a methanol molecule interacting with a protonated methanol ion via the elimination of a water molecule is a basic mechanism for the formation of complex organic molecules. Here, we experimentally examine such reactions in the gas phase, analyzing the production and reactivity of protonated cluster ions formed by the ionization of a supersonic jet of methanol. Focusing especially on the post-collisional relaxation of the protonated methanol dimer and trimer ions after high-energy single collisions, the results indicate a strong size selectivity favoring the occurrence of this reaction only in the dimer ion. To elucidate this behavior, the velocity distribution of the eliminated water molecule was measured using an event-by-event coincidence analysis. These results are interpreted using quantum chemical calculations of the dissociation pathways. It turns out that in the dimer case, two transition states are able to contribute to this intracluster reaction. In the trimer case, methanol evaporation appears as the most energetically favorable relaxation pathway.

Risk factors for allergy documentation in electronic health record: A retrospective study in a tertiary health center in Switzerland.

BACKGROUND: Most hospitals use electronic health records (EHR) to warn health care professionals of drug hypersensitivity (DH) and other allergies. Indiscriminate recording of patient self-reported allergies may bloat the alert system, leading to unjustified avoidances and increases in health costs. The aim of our study was to analyze hypersensitivities documented in EHR of patients at Lausanne University Hospital (CHUV). METHODS: We conducted a retrospective study on patients admitted at least 24 h to CHUV between 2011 and 2021. After ethical clearance, we obtained anonymized data. Because culprit allergen could be either manually recorded or selected through a list, data was harmonized using a reference allergy database before undergoing statistical analysis. RESULTS: Of 192,444 patients, 16% had at least one allergy referenced. DH constituted 60% of all allergy alerts, mainly beta-lactam antibiotics (BLA) (30%), NSAID (11%) and iodinated contrast media (ICM) (7%). Median age at first hospitalization and hospitalization length were higher in the allergy group. Female to male ratio was 2:1 in the allergic group. Reactions were limited to the skin in half of patients, and consistent with anaphylaxis in 6%. In those deemed allergic to BLA, culprit drug was specified in 19%, 'allergy to penicillin' otherwise. It was impossible to distinguish DH based on history alone or resulting from specialized work-up. CONCLUSIONS: Older age, longer hospital stays, and female sex increase the odds of in-patient allergy documentation. Regarding DH, BLA were referenced in 4% of inpatient records. Specific delabeling programs should be implemented to increase data reliability and patient safety.

Glycine Peptide Chain Formation in the Gas Phase via Unimolecular Reactions.

Peptide chain formation from amino acids such as glycine is a key step in the emergence of life. Unlike their synthesis by living systems, how peptide chains grow under abiotic conditions is an open question given the variety of organic compounds discovered in various astrophysical environments, comets and meteorites. We propose a new abiotic route in the presence of protonated molecular dimers of glycine in a cold gaseous atmosphere without further need for a solid catalytic substrate. The results provide evidence for the preferential formation of mixed protonated dimers of glycine consisting of a dipeptide and a glycine molecule instead of pure protonated glycine dimers. Additional measurements mimicking a cosmic-ray impact in terms of internal excitation show that a single gas-phase collision induces polymerization via dehydration in both the mixed and pure dimer ions. Peptide chain growth is thus demonstrated to occur via a unimolecular gas-phase reaction in an excited cluster ion.

Polyarteritis Nodosa: Old Disease, New Etiologies.

Polyarteritis nodosa (PAN), also known as panarteritis nodosa, represents a form of necrotizing vasculitis that predominantly affects medium-sized vessels, although it is not restricted to them and can also involve smaller vessels. The clinical presentation is heterogeneous and characterized by a significant number of patients exhibiting general symptoms, including asthenia, fever, and unintended weight loss. Although PAN can involve virtually any organ, it preferentially affects the skin, nervous system, and the gastrointestinal tract. Orchitis is a rare but specific manifestation of PAN. The absence of granulomas, glomerulonephritis, and anti-neutrophil cytoplasmic antibodies serves to distinguish PAN from other types of vasculitis. Major complications consist of hemorrhagic and thrombotic events occurring in mesenteric, cardiac, cerebral, and renal systems. Historically, PAN was frequently linked to hepatitis B virus (HBV) infection, but this association has dramatically changed in recent years due to declining HBV prevalence. Current epidemiological research often identifies a connection between PAN and genetic syndromes as well as neoplasia. This article provides a comprehensive review of PAN, specifically focusing on the progression of its clinical manifestations over time.

[Should we suspect immune deficiency in internal medicine hospitalized patients?] / Quand suspecter une immunodéficience chez le patient hospitalisé en médecine interne?

Although often overlooked immune deficiencies are more common than generally believed. The internist is frequently the first physician to potentially meet affected patients, playing a significant role in detecting these immune deficiencies, whether they are primary (congenital) or secondary (acquired). In both scenarios, early identification and intervention can greatly reduce the morbidity and mortality of these patients. In this article, we review common immune deficits, suggest initial assessments when indicative signs are present, and provide guidance for management.

Les déficits immunitaires, quoique souvent méconnus, sont plus fréquents qu'on ne le pense. L'interniste est fréquemment le premier médecin à entrer en contact avec des patients potentiellement atteints, jouant ainsi un rôle important dans la détection de ces maladies, qu'elles soient primaires (congénitales) ou secondaires (acquises). Dans les deux cas, une identification et une intervention précoces peuvent considérablement réduire la morbidité et la mortalité de ces patients. Dans cet article, nous passons en revue les déficits immuns fréquents, suggérons des bilans initiaux en présence de signes évocateurs et fournissons des orientations pour la prise en charge.

[Anti-glomerular basement membrane disease]. / Maladie des anticorps anti-membrane basale glomérulaire.

Anti-glomerular basement membrane disease is a rare disease. In its classical presentation it associates rapidly progressive glomerulonephritis and diffuse alveolar hemorrhage, linked to the presence of antibodies targeting type IV collagen in the glomerular and alveolar basal membrane. Anti-GBM disease warrants prompt medical management to limit permanent kidney damage and mortality. Treatment includes plasma exchanges to quickly remove pathogenic antibodies and immunosuppressants to stop their production. This article reviews the pathogenesis and current treatments.

La maladie des anticorps anti-membrane basale glomérulaire (anti-MBG) est une entité rare. Dans sa présentation classique, elle associe une glomérulonéphrite rapidement progressive et une hémorragie alvéolaire diffuse liée à des anticorps dirigés contre le collagène de type IV des membranes basales glomérulaire et alvéolaire. Les pronostics rénal et vital sont engagés. Le traitement doit être prompt et comprend des plasmaphérèses visant à éliminer les anticorps pathogéniques ainsi qu'une immunosuppression destinée à supprimer leur production. Cet article passe en revue la pathogénie et les traitements actuels.

[Granulomatosis with polyangiitis: what's new?] / Granulomatose avec polyangéite : quoi de neuf ?

Within the group of antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides, granulomatosis with polyangiitis (GPA) is the most frequent. The incidence is around 10 to 20 cases/million/year. Clinical manifestations are varied, with ENT, lungs and kidneys most frequently involved. ANCA are pathogenic by triggering neutrophil activation, which leads to vascular damage. Detection of ANCA is most helpful in establishing the diagnosis, but serology may be negative in GPA limited to the airways. Diagnostic work-up and therapy require a multidisciplinary approach. Treatment includes an induction and maintenance phase, combining corticosteroids and immunosuppressive drugs. It aims at limiting the risk of relapses, which is important in GPA, and at reducing corticosteroids toxicity.

La granulomatose avec polyangéite (GPA) fait partie des vasculites associées aux anticorps anti-cytoplasme des polynucléaires neutrophiles (ANCA). La maladie touche principalement la sphère ORL, les poumons et les reins. Son incidence est de 10 à 20 cas/million/année. Les ANCA sont pathogéniques en induisant une activation des polynucléaires neutrophiles, entraînant des lésions endothéliales. Le diagnostic est facilité par la détection des ANCA, qui peuvent cependant être absents dans les formes ORL limitées. La prise en charge est multidisciplinaire. Le traitement comprend une phase d'induction et une autre de maintien de la rémission, associant corticostéroïdes et immunosuppresseurs. L'objectif du traitement est de limiter le risque important de rechute et de réduire la toxicité des corticostéroïdes.

[Chronic rhinosinusitis with nasal polyps†: is there a place for monoclonal antibodies in 2020†?] / Allergologie-immunologie - Rhinosinusite chronique avec polypes nasaux†: quelle est la place des anticorps monoclonaux en 2020†?

Chronic rhinosinusitis with nasal polyps is a severe form of chronic rhinosinusitis, which has a strong negative impact on quality of life. Rhinoscopy is helpful for diagnosis, and initial management depends on intra-nasal corticosteroids and sometimes short-term oral corticosteroids (1 to 3 weeks). If well-conducted drug therapy fails, surgery is considered. In the event of post-surgery recurrence or in case of concomitant severe asthma, biologic therapies represent an interesting option. These drugs include dupilumab, mepolizumab, benralizumab and omalizumab. The choice of medication depends on the individual patient context, which includes the presence of atopic dermatitis, eosinophilia, or asthma.

La rhinosinusite chronique avec polypes nasaux constitue une forme sévère de rhinosinusite chronique qui a un impact significatif sur la qualité de vie des personnes affectées. La rhinoscopie aide à poser le diagnostic et la prise en charge initiale repose sur les corticostéroïdes intranasaux avec parfois de courtes cures de corticostéroïdes per os (1 à 3 semaines). En cas d'échec du traitement médicamenteux bien conduit, la chirurgie est envisagée. Lors de récurrence après chirurgie ou en présence d'un asthme difficile à contrôler, les médicaments biologiques constituent une alternative intéressante. Ceux-ci comprennent notamment le dupilumab, le mépolizumab, le benralizumab et l'omalizumab. Le choix de la molécule sera dicté par le contexte individuel du patient, en fonction de la présence d'une dermatite atopique, d'une éosinophilie ou d'un asthme associé.

[Biologics and systemic lupus erythematosous : new insights and perspectives]. / Biologiques et lupus érythémateux systémique : nouveautés et perspectives.

Systemic lupus erythematosus is a complex autoimmune disease that remains challenging to treat. Recent advances in the understanding of the pathogenesis of SLE pave the way for the evaluation of biologic medicine. The most promising therapeutic targets in SLE are those that interfere with B cells count or normal function, interferon inhibitors, JAK inhibitors and biologicals that alter the cytokines imbalance that characterizes SLE. Recent phase 3 clinical trials have evaluated the role of belimumab in lupus nephritis and the usefulness of anifrolumab in the treatment of moderate to severe SLE. Many more trials are currently underway and may improve the level of care of patients with SLE in the near future.

Le lupus érythémateux systémique (LES) est une maladie autoimmune complexe, dont le traitement reste un challenge. Les progrès récents sur les connaissances de l'immunopathologie du LES ont permis d'évaluer la place de nouveaux traitements biologiques dans des études cliniques. Celles-ci concernent les anticorps monoclonaux antilymphocytes B, les inhibiteurs de l'interféron et des Janus kinases, ou encore les traitements par administration de cytokines, comme l'interleukine 2. Des études de phase 3 récentes ont évalué la place du bélimumab dans le traitement de la néphrite lupique et l'utilité du blocage de l'interféron par l'anifrolumab dans le traitement du LES modéré à sévère. Plusieurs études cliniques en cours pourraient révolutionner la prise en charge des patients atteints d'un LES dans les années à venir.

[COVID-19 vaccines: vaccine targets, immunogenicity and allergic reactions]. / Vaccins contre le Covid-19 : cibles vaccinales, immunogénicité et réactions allergiques.

Many vaccine strategies have been developed to control the COVID-19 pandemic. This article presents the mechanisms of action and the efficacy of different vaccines including mRNA- and adenovirus-based vaccines. We will discuss the different vaccine targets, immune responses and allergic reactions which have been reported during the vaccination campaigns. Finally, the latest recommendations for the prevention and management of severe allergic reactions will be summarized.

De nombreuses stratégies vaccinales ont été développées pour tenter de contrôler la pandémie de Covid-19. Cet article présente le fonctionnement et l'efficacité de différents vaccins, en particulier ceux à ARN messager et adénovecteurs. Nous discutons des cibles vaccinales, des véhicules vaccinaux ainsi que de l'immunité qu'ils induisent. Nous nous penchons également sur la question des allergies aux vaccins qui a rapidement été soulevée après le début des campagnes de vaccination à large échelle. Les allergènes potentiellement en cause et les mécanismes impliqués sont discutés. Enfin, nous proposons des recommandations pour la prévention et la prise en charge des réactions allergiques sévères.

[Autoimmune hepatitis: 2021 update]. / Hépatite autoimmune : mise au point 2021.

Autoimmune hepatitis is a rare disease which can present as acute or chronic forms and can be difficult to diagnose due to its variable clinical presentation. The disease arises in genetically susceptible individuals and several triggers have been identified. The diagnosis is based on the presence of autoantibodies, elevated transaminases and serum immunoglobulin G levels as well as a compatible histology. First-line immunosuppressive treatment strategies lead to clinical remission in most patients. In case of non-response, second-line therapies can be used and in case of hepatocellular insufficiency, liver transplantation remains an excellent option.

L'hépatite autoimmune est une maladie rare, pouvant se présenter sous forme aiguë ou chronique et dont le diagnostic peut être difficile à poser en raison d'une présentation clinique variable. La maladie se développe chez des personnes génétiquement prédisposées et plusieurs événements déclencheurs ont été identifiés. Le diagnostic repose sur la présence d'autoanticorps spécifiques, d'une élévation des transaminases et des immunoglobulines G, ainsi que sur une histologie compatible. Les traitements de première ligne, immunosuppresseurs, permettent dans la plupart des cas d'obtenir une rémission clinique. En cas de non-réponse, des traitements de deuxième ligne sont disponibles et lors d'insuffisance hépatocellulaire, la transplantation hépatique reste une excellente option.

[Autoimmune diseases in the context of pandemic COVID-19]. / Maladies autoimmunes dans le contexte de la pandémie COVID-19.

Patient suffering from autoimmune diseases (AID) typically have an increased risk of infection, which is attributed to the disease itself, but also to immunosuppressive drugs (IS) and comorbidities. During the current COVID-19 outbreak, the way to manage these diseases remains elusive. Limited data is currently available on AID and IS in the context of this new coronavirus infection. To date, there is no evidence to support an increase in complications of COVID-19 in these patients. In addition, certain drugs that are commonly used to treat AID could be part of the therapeutic arsenal used in COVID-19. The purpose of this article is to review the unique aspects of patients with AID during the COVID-19 outbreak.

Les patients atteints de maladies autoimmunes (MAI) présentent classiquement un risque accru d'infections, qui est attribué à la maladie en tant que telle, mais aussi aux traitements immunosuppresseurs (IS) et aux comorbidités. Durant l'épidémie COVID-19, l'attitude à adopter par rapport à ces maladies et à leur traitement reste incertaine. En effet, les données concernant les MAI et l'IS dans le cadre de cette nouvelle infection à coronavirus restent encore très limitées. À l'heure actuelle, il n'y a pas d'évidence indiquant une augmentation des complications sévères en lien avec le COVID-19 chez ces patients. De plus, certains médicaments utilisés pour traiter les MAI pourraient faire partie de l'arsenal thérapeutique utilisé en cas d'infection par le COVID-19. Cet article passe en revue les aspects particuliers des patients souffrant de MAI durant l'épidémie COVID-19.

Signaling lymphocyte activation molecule family in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease characterized by a breakdown in immune tolerance leading to the development of auto-reactive lymphocytes and autoantibodies. Recent findings have provided new insight on the role of the signaling lymphocytic activation molecule family (SLAMF) receptors, a group of nine co-regulatory molecules involved in the activation of hematopoietic cells, and their downstream protein SLAM-associated protein (SAP), into the pathogenesis of SLE. This review summarizes the current knowledge on SLAMF in human SLE immunopathogenesis, and the importance of SLAMF molecules as new therapeutic targets.

Engagement of SLAMF3 enhances CD4+ T-cell sensitivity to IL-2 and favors regulatory T-cell polarization in systemic lupus erythematosus.

Signaling lymphocytic activation molecule family 3 (SLAMF3/Ly9) is a coregulatory molecule implicated in T-cell activation and differentiation. Systemic lupus erythematosus (SLE) is characterized by aberrant T-cell activation and compromised IL-2 production, leading to abnormal regulatory T-cell (Treg) development/function. Here we show that SLAMF3 functions as a costimulator on CD4(+) T cells and influences IL-2 response and T helper cell differentiation. SLAMF3 ligation promotes T-cell responses to IL-2 via up-regulation of CD25 in a small mothers against decapentaplegic homolog 3 (Smad3)-dependent mechanism. This augments the activation of the IL-2/IL-2R/STAT5 pathway and enhances cell proliferation in response to exogenous IL-2. SLAMF3 costimulation promotes Treg differentiation from naïve CD4(+) T cells. Ligation of SLAMF3 receptors on SLE CD4(+) T cells restores IL-2 responses to levels comparable to those seen in healthy controls and promotes functional Treg generation. Taken together, our results suggest that SLAMF3 acts as potential therapeutic target in SLE patients by augmenting sensitivity to IL-2.

[Autoimmune disorders during chronic human immunodeficiency virus (HIV) infection]. / Manifestations auto-immunes au cours de l'infection chronique par le virus de l'immunodéficience humaine (VIH).

Over the years, the challenges of chronic HIV infection have evolved from the management of life-threatening opportunistic infections to chronic noninfectious complications. Nowadays, autoimmune disorders, which are linked to chronic immune dysregulations, have become an important issue in HIV infected patients. Although they mimic disorders and syndromes described in HIV seronegative patients, their frequency and clinical picture may differ considerably. The various immunological alterations and the production of non-specific autoantibodies often make diagnosis difficult. Moreover, the introduction of immunosuppressive therapy requires careful consideration in the presence of a chronic infection that alters the cellular immunity and increases the risk of infections.

Au fil des années, les défis concernant l'approche de l'infection chronique par le virus VIH ont évolué de la prise en charge d'infections opportunistes fatales vers des complications non infectieuses chroniques. Parmi ces complications, de multiples manifestations auto-immunes sont décrites. Celles-ci sont liées aux dysrégulations immunitaires induites par l'infection virale chronique. Bien qu'elles ressemblent aux maladies et syndromes décrits chez les patients VIH séronégatifs, leur fréquence et leur présentation clinique peuvent être considérablement différentes. Les altérations immunologiques et la production d'autoanticorps non spécifiques rendent le diagnostic difficile. Finalement, l'introduction d'un traitement immunosuppresseur doit faire l'objet d'une réflexion pondérée, en présence d'une infection virale chronique qui altère l'immunité et met potentiellement le patient à risque élevé d'infection.

[From isolated cutaneous vasculitis to systemic disease†: a diagnostic approach to purpura in the adult patient]. / De la vasculite cutanée isolée aux atteintes systémiques†: l'approche diagnostique d'un purpura chez l'adulte.

Purpura can be a clinical manifestation of various diseases. The causes of purpura are divided into two main categories: thrombocytopenia and vasculopathies. Cutaneous vasculitis belongs to the latter group. Cutaneous vasculitis should be considered a symptom rather than a medical entity. Some forms of cutaneous vasculitis are limited to the skin and are known as isolated cutaneous vasculitis, while other forms may be part of a systemic disease with a more serious prognosis. It is essential to clarify the type and severity of the disease for optimal patient care. A delay in the identification and start of treatment can be the cause of serious and potentially irreversible complications. Through this article, we will propose a step-by-step approach from diagnosis to patient care.

Le purpura peut être la manifestation d'un large spectre de pathologies. Les causes sont généralement séparées en deux groupes principaux : les thrombopénies et les vasculopathies, dont fait partie la vasculite cutanée. Elle doit être considérée comme un symptôme plutôt que comme une entité en soi. Certaines formes peuvent être limitées à la peau alors que d'autres s'inscrivent dans un tableau systémique, potentiellement de mauvais pronostic. Savoir clarifier le type et la sévérité des atteintes est important pour la prise en charge optimale du patient. Un diagnostic précis et précoce est essentiel afin d'éviter des complications sévères et potentiellement irréversibles. A travers cet article, nous proposons un algorithme de raisonnement pour porter le diagnostic étiologique d'un purpura et proposer une prise en charge adaptée.

[Side effects of immune checkpoint inhibitors: diagnosis and management]. / Effets indésirables des inhibiteurs de points de contrôle immunitaire : diagnostic et prise en charge.

New oncological approaches using immune checkpoint inhibitors aim to reinvigorate lymphocytes against the tumor. The prognosis of cancer has been significantly improved by these treatments, which nonetheless lead to a new spectrum of immune-related side effects. The most frequent are skin rash, colitis, thyroid dysfunction, hypophysitis, hepatitis and pneumonitis. Early detection of these toxicities is crucial to determine the etiology and to introduce a temporary immunosuppressive therapy, allowing resolution of toxicity in most of cases. A multidisciplinary team is essential for optimal management.

Les nouvelles thérapies oncologiques, dont les inhibiteurs de points de contrôle immunitaire, permettent une stimulation lymphocytaire antitumorale. Ces traitements ont amélioré de manière significative le pronostic oncologique de nombreux patients, mais présentent néanmoins un nouveau spectre de toxicités, d'ordre immunologique. Les toxicités immunes les plus fréquentes sont le rash cutané, la colite, la dysthyroïdie, l'hypophysite, l'hépatite et la pneumonie. Une détection précoce de ces effets secondaires est cruciale afin de réaliser un bilan étiologique adéquat puis d'introduire un traitement immunosuppresseur temporaire, qui permet une résolution de la toxicité dans la grande majorité des cas. Une évaluation multidisciplinaire est souvent indispensable pour une prise en charge optimale.

SLE-Associated Defects Promote Altered T Cell Function.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease linked to profound defects in the function and phenotype of T lymphocytes. Here, we describe abnormal signaling pathways that have been documented in T cells from patients with SLE and discuss how they impact gene expression and immune function, in order to understand how they contribute to disease development and progression.