[CAR-T therapy for autoimmune diseases]. / Thérapie cellulaire CAR-T dans le traitement des maladies auto-immunes.

Cellular therapy using genetically modified T lymphocytes expressing synthetic receptors, known as CAR (Chimeric Antigen Receptor), has revolutionized the treatment of certain hematologic malignancies. This success has led to exploring the same approach in the treatment of severe autoimmune diseases refractory to conventional therapies. Initial results in systemic lupus erythematosus have shown complete remissions that appear to persist over time. Consequently, there is a growing number of ongoing clinical trials. In this review, we discuss the rationale behind the use of CAR-T therapies, the targeted autoimmune diseases, and the associated risks.

La thérapie cellulaire à base de lymphocytes T génétiquement modifiés exprimant des récepteurs synthétiques ou CAR (récepteur antigénique chimérique) a révolutionné le traitement de certaines maladies hémato-oncologiques. Ce succès a conduit à l'exploration de la même approche dans le traitement de maladies auto-immunes sévères et réfractaires aux thérapies conventionnelles. Les premiers résultats obtenus dans le lupus érythémateux systémique ont montré des rémissions complètes semblant persister dans le temps. Nous assistons donc actuellement à une prolifération importante d'essais cliniques. Dans cet article, nous abordons le rationnel derrière l'utilisation des thérapies CAR-T, les maladies auto-immunes ciblées, mais aussi les risques associés.

[Understanding hypersensitivity reactions to monoclonal antibodies]. / Comprendre les réactions d'hypersensibilité aux anticorps monoclonaux.

Biologic drugs are complex molecules synthesized by a living organism. Their use is increasingly prevalent across all medical specialties, exposing a growing number of patients to potential adverse reactions. In this review, we discuss the new classification of hypersensitivity reactions, along with the specific characteristics of monoclonal antibodies. We also address the available diagnostic tools and discuss the management of those reactions, including for patients requiring the continuation of these biologic drugs.

Les médicaments biologiques sont des molécules complexes synthétisées par un organisme vivant. Ils sont de plus en plus utilisés dans toutes les spécialités médicales, exposant ainsi les patients à des réactions indésirables. Dans cet article, nous abordons la nouvelle classification des réactions d'hypersensibilité ainsi que les caractéristiques spécifiques des anticorps monoclonaux. Nous évoquons également les outils diagnostiques disponibles et discutons de la prise en charge, y compris pour les patients nécessitant la poursuite de l'administration des médicaments biologiques.

Intradermal skin test with mRNA vaccines as a surrogate marker of T cell immunity in immunocompromised patients.

OBJECTIVES: Intradermal skin test (IDT) with mRNA vaccines may represent a simple, reliable, and affordable tool to measure T cell response in immunocompromised patients who failed to mount serological responses following vaccination with mRNA covid-19 vaccines. METHODS: We compared anti-SARS-CoV-2 antibodies and cellular responses in vaccinated immunocompromised patients (n = 58), healthy seronegative naive controls (NC, n = 8), and healthy seropositive vaccinated controls (VC, n = 32) by Luminex, spike-induced IFN-γ Elispot and an IDT. A skin biopsy 24 h after IDT and single-cell RNAseq was performed in three vaccinated volunteers. RESULTS: Twenty-five percent of seronegative NC had a positive Elispot (2/8) and IDT (1/4), compared to 95% (20/21) and 93% (28/30) in seropositive VC, respectively. Single-cell RNAseq data in the skin of VC showed a predominant mixed population of effector helper and cytotoxic T cells. The TCR repertoire revealed 18/1064 clonotypes with known specificities against SARS-CoV-2, among which six were spike-specific. Seronegative immunocompromised patients with positive Elispot and IDT were in 83% (5/6) treated with B cell-depleting reagents, while those with negative IDT were all transplant recipients. CONCLUSIONS: Our results indicate that delayed local reaction to IDT reflects vaccine-induced T-cell immunity opening new perspectives to monitor seronegative patients and elderly populations with waning immunity.

Atopy as an independent predictor for long-term patient and graft survival after kidney transplantation.

Background: Atopy is a genetic condition predisposing individuals to develop immunoglobulin E (IgE) against common allergens through T-helper 2 (Th2) polarization mechanisms. The impact of atopy on graft survival in solid organ transplantation is unknown. Methodology: We analyzed 268 renal allograft recipients from the Swiss Transplant Cohort Study, a prospective multicenter cohort studying patients after solid organ transplantation, with a 9-year median follow-up (IQR 3.0). We used the Phadiatop assay to measure IgE antibodies against a mixture of common inhaled allergens (grass, tree, herbs, spores, animals, and mites) to identify pre-transplantation atopic patients (>0.35 KU/L). Results: Of 268 kidney transplant recipients, 66 individuals were atopic (24.6%). Atopic patients were significantly younger than non-atopic patients (49.6 vs 58.0 years old, P = 0.002). No significant difference was found for gender, cold/warm ischemia time, preformed donor-specific antibodies (DSA), HLA mismatches, induction and maintenance immunosuppressive therapy, CMV serostatus, or cause of kidney failure. Patient and graft survival at ten years of follow-up were significantly better in the atopic group, 95.2% versus 69.2% patient survival (P < 0.001), and 87.9% versus 60.8% graft survival (P < 0.001), respectively. A multivariate Cox analysis revealed that atopy predicted recipient and graft survival independently of age and living donor donation. Finally, we found similar rates of biopsy-proven acute cellular and antibody-mediated rejections between atopic and non-atopic recipients. Conclusion: Atopy was associated with better long-term patient and graft survival, independently of age and living donor donation after kidney transplantation. Yet, atopy should not be used as a predictor for acute rejection.

Chimeric antigen receptor T-cell therapy for HIV cure.

PURPOSE OF REVIEW: Cell-based immunotherapies have made enormous progress over the last decade with the approval of several anti-CD19-chimeric antigen receptor (CAR)-T cell therapies for haemato-oncological diseases. CARs are synthetic receptors comprising an antigen-specific extracellular domain fused to a hinge, transmembrane and intracellular signalling domains. The success obtained with CD19 CAR-T cells rekindled interest in using CAR-T cells to treat HIV seropositive patients. The purpose of this review is to discuss historical and recent developments of anti-HIV CARs. RECENT FINDINGS: Since the first description of CD4+-based CARs in the early 90s, new generations of anti-HIV CARs were developed. They target the hetero-trimeric glycoprotein gp120/gp41 and consist of either a CD4+ extracellular domain or a VH/VL segment derived from broadly neutralizing antibodies. Recent efforts were employed in multiplexing CAR specificities, intracellular signalling domains and T cells resistance to HIV. SUMMARY: Several new-anti HIV CAR-T cells were successfully tested in preclinical mice models and are now waiting to be evaluated in clinical trials. One of the key parameters to successfully using CAR-T cells in HIV treatment will depend on their capacity to control the HIV reservoir without causing off-targeting activities.

[MMR vaccination at UNIL and EPFL†: Lausanne medical students get involved]. / Vaccination ROR à l'UNIL et à l'EPFL†: les étudiant·e·s en médecine de Lausanne se mobilisent.

In recent years, several cases of measles have appeared on the campuses of the University of Lausanne (UNIL) and the Swiss Federal Institute of Technology in Lausanne (EPFL). In response to this, several medical students have mobilized in collaboration with various cantonal authorities in order to set up a free measles, mumps and rubella vaccination campaign on the UNIL/EPFL campuses, in 2019. This first edition was a success and will be repeated in the future. Such an approach having shown its feasibility, it could be applied to other public health issues. The involvement of medical students could thus be extremely valuable if a generalized vaccination against SARS-CoV-2 were to take place.

Durant ces dernières années, plusieurs cas de rougeole sont apparus sur les campus de l'Université de Lausanne (UNIL) et de l'École polytechnique fédérale de Lausanne (EPFL). En réponse à cela, plusieurs étudiant·e·s en médecine se sont mobilisé·e·s en collaboration avec diverses instances cantonales afin de mettre en place en 2019 une campagne de vaccination gratuite contre la rougeole, les oreillons et la rubéole sur les campus UNIL/EPFL. Cette première édition a été un succès et sera reconduite dans le futur. Une telle approche ayant montré sa faisabilité, elle pourrait être appliquée à d'autres enjeux de santé publique. L'implication des étudiant·e·s en médecine pourrait ainsi être extrêmement précieuse si une vaccination généralisée contre le virus SARS-CoV-2 devait avoir lieu.

[Racism and the practice of medicine†: elements for a required learning]. / Racisme et pratique de la médecine†: éléments pour un apprentissage nécessaire.

The new catalogue of objectives for medical education at Swiss universities (PROFILES) underlines the importance of teaching the impact of ethnic, cultural, spiritual and religious differences and the socio-economic determinants of health and illness on health and care. At the same time, the social reality of the moment reminds us that racism is still present in our societies. Therefore, education for medical students is necessary. This should include basic knowledge but also, and above all, an understanding of the underlying mechanisms that will enable them to grasp the notions of prejudice, stereotypes and discrimination. Finally, introspection, the acquisition of cross-cultural skills and cultural humility will help to deal with this other epidemic.

Le nouveau catalogue des objectifs d'enseignement de la médecine dans les universités suisses (PROFILES) souligne l'importance de l'enseignement de l'impact sur la santé et les soins des différences ethniques, culturelles, spirituelles, religieuses, et des déterminants socio-économiques de la santé et de la maladie. Parallèlement, la réalité sociale du moment nous rappelle que le racisme est toujours présent dans nos sociétés. Dès lors, un enseignement aux étudiant·e·s de médecine est nécessaire. Celui-ci devra intégrer des connaissances de base mais aussi et surtout la compréhension des mécanismes sous-jacents qui permettra d'appréhender les notions de préjugés, stéréotypes et discriminations. Enfin, l'introspection, l'acquisition de compétences transculturelles et d'humilité culturelle permettront de faire face à cette autre épidémie.

[Medical students at the bedside of COVID-19 patients†: motivations and challenges]. / Étudiant·e·s en médecine engagé·e·s au chevet des patient·e·s hospitalisé·e·s pour COVID-19 - Motivations et enjeux.

The SARS-CoV-2 pandemic is putting our healthcare system under exceptional pressure, given the number of affected patients. In a context of limited human healthcare resources, senior medical students represent a valuable workforce that can quickly be mobilized for patient care. This is the approach followed in Switzerland and other countries, in several outpatient structures or inpatient services, including the Department of Internal Medicine, of the Lausanne University Hospital (CHUV). In this article, we first give the floor to students who responded to our call. We conclude with important considerations in terms of students' clinical supervision. It is reminded that the involvement of students in the care of COVID-19 patients should only occur on a vo luntary basis.

La pandémie de COVID-19 met notre système de santé sous une pression exceptionnelle, au vu du nombre de patient·e·s atteint·e·s. Dans un contexte de ressources humaines médico-soignantes limitées, les étudiant·e·s en médecine avancé·e·s dans leur cursus représentent un renfort très précieux, rapidement mobilisable auprès des patient·e·s. C'est la démarche suivie en Suisse et ailleurs dans le monde par diverses structures ambulatoires ou services hospitaliers, dont le Service de médecine interne du Centre hospitalier universitaire vaudois (CHUV). Dans cet article, nous donnons tout d'abord la parole aux étudiant·e·s qui ont répondu à notre appel. Nous terminons par des considérations importantes quant à l'accueil et l'accompagnement de ces étudiant·e·s. Il est rappelé que l'engagement d'étudiant·e·s auprès de patient·e·s souffrant de COVID-19 devrait se faire sur une base volontaire uniquement.