Axes de recherche
A retrospective study on the true prevalence of allergy to beta-lactam antibiotics in an adult population in Switzerland
Background: Studies suggest that 90% of patients labelled as allergic to penicillin tolerate it after rigorous assessment. Here, we examined the true frequency of allergies to beta-lactam antibiotics subclasses, as well as the negative predictive value (NPV) of skin testing in an adult population referred to a university allergy clinic in Switzerland.
Methods: This is a retrospective study in which we examined the clinical records of patients who were investigated for a label of allergy to beta-lactam (penicillin, cephalosporin or carbapenem) antibiotics between January 1st 2011 and December 31st 2018.
Results: 582 patients were identified with a documented allergy to beta-lactam antibiotics and 477 patients were systemically investigated by skin tests and/or drug challenge to confirm or rule out allergy. 262 patients reported a history of immediate reactions, 137 of delayed reactions, and 114 of unknown reactions. Overall, 88 (15.1%) patients were truly allergic to any beta-lactam antibiotics; 64 (11.0%) with an immediate reaction and 24 (4.1%) with a delayed reaction. Most frequently identified true allergy was penicillin (65 patients), followed by cephalosporin (21 patients) and carbapenem (2 patients). NPV of skin tests for all beta-lactam were 97.7% and 92.5% for immediate and delayed reactions, respectively, and 96.3% and 92.1% when penicillin was considered. Systemic allergic reaction occurred in 0.6% of skin tests and in 3.1% of drug challenges.
Conclusions: Only 15.1% of patients with beta-lactam allergy label are truly allergic and non-allergic patients can be safely identified and delabelled by a rigorous allergic work-up based on skin tests and drug challenge.
A retrospective study on the role of soluble CD25 in autoimmune and inflammatory diseases, with a focus on sarcoidosis.
Identifying circulating biomarkers is crucial for diagnosing autoimmune and inflammatory diseases. Soluble CD25 (sCD25), a marker of T-cell activation, has been linked to disease activity in various conditions, including being significantly elevated in hemophagocytic lymphohistiocytosis (HLH) and associated with disease severity in autoimmune diseases like lupus and Sjögren’s syndrome. Sarcoidosis, a multisystem inflammatory disease with diverse manifestations, lacks a definitive diagnostic test, making diagnosis challenging. Diagnosis relies on clinical presentation, exclusion of similar diseases, and histological findings, with blood biomarkers like sCD25 being investigated for their diagnostic potential, especially in sarcoidosis. Our study aims to explore sCD25's effectiveness as a biomarker for inflammatory diseases, focusing on sarcoidosis due to the current gaps in knowledge.
Retrospective study on the prevalence and clinical implications of positive ANA results in patients hospitalized in internal medicine.
Antinuclear antibody (ANA) screening is key in diagnosing and managing systemic and autoimmune diseases, notably Systemic Lupus Erythematosus and Sjögren’s disease. It involves a two-step process: determining ANA concentration through dilution titers and identifying fluorescence patterns, primarily via indirect immunofluorescence assay on HEp-2 cells, with enzyme-linked immunosorbent assay as a less preferred alternative due to lower sensitivity and specificity. The combination of titer and pattern is crucial for assessing disease nature and severity.
Clinical context is essential for test prescription and interpretation, as positive ANA results, which can occur in healthy individuals, require careful evaluation against clinical evidence. Inter-laboratory variability also affects ANA test reliability, necessitating consistent methods within laboratories to ensure accuracy.
This study focuses on the role of positive ANA tests in hospitalized patients' diagnosis, clinical outcomes, and management, aiming to refine the understanding of ANA test interpretation complexities for clinicians.
Restoration of NK Cell Cytotoxic Function With Elotuzumab and Daratumumab Promotes Elimination of Circulating Plasma Cells in Patients With SLE
Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease characterized by multiple cellular and molecular dysfunctions of the innate and adaptive immunity. Cytotoxic function of NK cells is compromised in patients with SLE. Herein, we characterized the phenotypic alterations of SLE NK cells in a comprehensive manner to further delineate the mechanisms underlying the cytotoxic dysfunction of SLE NK cells and identify novel potential therapeutic targets. Therefore, we examined PBMC from SLE patients and matched healthy controls by single-cell mass cytometry to assess the phenotype of NK cells. In addition, we evaluated the cell function of NK cells (degranulation and cytokine production) and the killing of B cell subpopulations in a B cell-NK cell in vitro co-culture model. We found that SLE NK cells expressed higher levels of CD38 and were not able to adequately upregulate SLAMF1 and SLAMF7 following activation. In addition, ligation of SLAMF7 with elotuzumab or of CD38 with daratumumab on SLE NK cells enhanced degranulation of both healthy and SLE NK cells and primed them to kill circulating plasma cells in an in vitro co-culture system. Overall, our data indicated that dysregulated expression of CD38, SLAMF1 and SLAMF7 on SLE NK cells is associated with an altered interplay between SLE NK cells and plasma cells, thus suggesting their contribution to the accumulation of (auto)antibody producing cells. Accordingly, targeting SLAMF7 and CD38 may represent novel therapeutic approaches in SLE by enhancing NK cell function and promoting elimination of circulating plasma cell.
Exploring NK Cell Mitochondrial Dysfunction in Lupus and Potential Treatments
Systemic lupus erythematosus (SLE) is a complex autoimmune disease marked by immune system imbalances, leading to decreased and dysfunctional Natural Killer (NK) cells. Our research focuses on understanding how mitochondrial health impacts NK cell performance in SLE patients compared to healthy individuals. We found that SLE NK cells have larger, yet less active mitochondria with increased superoxide production and structural abnormalities. Initial studies show mitochondrial DNA buildup and a decrease in mitochondrial clearance proteins in these cells, suggesting impaired lysosomal function could play a role. We're investigating the molecular pathways involved and testing treatments like Hydroxychloroquine and Urolithin A, which show promise in improving mitochondrial and lysosomal function in NK cells.
Pathogenèse du LES
Notre activité de recherche s'intéresse aux altérations du système immunitaire inné et adaptatif qui conduisent au développement d'auto-immunité dans le cadre du lupus érythémateux systématique (LES). Le LES est une maladie inflammatoire auto-immune, dans laquelle une perte de tolérance mène à la production de cellules auto-réactives et d'auto-anticorps. Ceux-ci qui produisent des dégâts tissulaires qui peuvent toucher tous les organes. Nos recherches visent à comprendre la pathogenèse de la maladie et à identifier des cibles thérapeutiques nouvelles et spécifiques.
Nous travaillons essentiellement sur les cellules immunitaires isolées à partir du sang périphérique de patients avec LES, ainsi que sur des prélèvements tissulaires que nous caractérisons par en laboratoire. Les techniques de laboratoires utilisées concernent principalement l'immunologie cellulaire (culture cellulaire, cytométrie de flux, cytométrie de masse, séquençage d'ARN, analyses du métabolisme cellulaire, microscopie...). Différents projets sont actuellement en cours (analyses de l'intéraction entre cellules NK et cellules productrices d'auto-anticorps, analyses des altérations qui caractérisent les cellules T follicular helper chez les patients avec LES...)
