•CAR-T cells show rapid and prolonged remission in severe lupus patients.•CAR-T cells may offer a steroid-free alternative in several autoimmune diseases.•Challenges like technical complexity, ...accessibility and cost persist.•Rigorous assessment within controlled clinical trials is now required.
Chimeric Antigen Receptor T-cell therapy (CAR-T), currently employed routinely for treating B-cell malignancies, has emerged as a groundbreaking approach in addressing severe autoimmune diseases, especially for systemic lupus erythematosus (SLE). The immunological rationale for targeting B lymphocytes in autoimmune diseases is well-established, demonstrating success in numerous autoantibody-mediated autoimmune conditions through targeted therapies over several years. However, this approach has often proven ineffective in the context of systemic lupus erythematosus. Recent data on CAR-T usage in lupus, revealed promising results including rapid and prolonged remission without treatment, highlighting the potential of CAR-T therapy in severe lupus cases. This article provides a comprehensive overview of CAR-T cells, tracing their evolution from hematological malignancies to their recent applications in autoimmune disorder, especially in lupus. Clinical trials within a regulated framework are now imperative to assess the procedural aspects in order to validate the considerable promise of CAR-T cell therapy in the field of autoimmune diseases. This includes evaluating safety and long-term efficacy and security of the procedure, the benefit-risk ratio in the field of autoimmunity, the availability and cost-related issues associated with this emerging cellular therapy procedure.
The field of primary immunodeficiencies (PIDs) is rapidly evolving. Indeed, the number of described diseases is constantly increasing thanks to the rapid identification of novel genetic defects by ...next-generation sequencing. PIDs are now rather referred to as "inborn errors of immunity" due to the association between a wide range of immune dysregulation-related clinical features and the "prototypic" increased infection susceptibility. The phenotypic spectrum of PIDs is therefore very large and includes several orofacial features. However, the latter are often overshadowed by severe systemic manifestations and remain underdiagnosed. Patients with impaired innate immunity are predisposed to a variety of oral manifestations including oral infections (e.g., candidiasis, herpes gingivostomatitis), aphthous ulcers, and severe periodontal diseases. Although less frequently, they can also show orofacial developmental abnormalities. Oral lesions can even represent the main clinical manifestation of some PIDs or be inaugural, being therefore one of the first features indicating the existence of an underlying immune defect. The aim of this review is to describe the orofacial features associated with the different PIDs of innate immunity based on the new 2019 classification from the International Union of Immunological Societies (IUIS) expert committee. This review highlights the important role played by the dentist, in close collaboration with the multidisciplinary medical team, in the management and the diagnostic of these conditions.
•We present three cases of granulomatous manifestations following the onset of COVID19•Granuloma formation could translate an effective response via the renin-angiotensin and innate immune ...systems•Targeting of the renin-angiotensin system or MAIT cells could therefore be interesting in both diseases.
The management of lymphoma in patients with primary immunodeficiency (PID) is challenging because of its poor prognosis and complex therapeutic approaches. We conducted a systematic literature review ...of case-reports, case-series, and cohorts indexed in MEDLINE reporting the association of lymphoma and PID. One hundred and eighty-two articles were selected out of 787. We identified 386 cases. Median age at diagnosis of PID and lymphoma was 9.5 and 12 years old, respectively. T-cell deficiencies were the main PIDs associated with lymphoma (57%). The most prevalent lymphoma was diffuse large B-cell lymphoma (33.5%). Epstein-Barr Virus-driven lymphomas were mostly observed in innate immunodeficiencies (when reported). Complete response to treatment was observed in 65.8% of the cases. Death occurred in 38.2%. Few allogenic stem cell transplantations were performed (29 cases). Our detailed analysis of the literature provides a landscape of lymphoma's occurrence in PID. Devoted studies in specific sub-groups of patients at risk are needed to develop dedicated protocols.
It is now widely accepted that antiphospholipid antibodies (aPL) have direct pathogenic effects and that B cells, notably through aPL production, play a key role in the development of ...antiphospholipid syndrome (APS). Recent findings strengthened the implication of B cells with the description of specific B cell phenotype abnormalities and inborn errors of immunity involving B cell signaling in APS patients. In addition, it has been shown in preclinical models that cross-reactivity between APS autoantigens and mimotopes expressed by human gut commensals can lead to B cell tolerance breakdown and are sufficient for APS development. However, B cell targeting therapies are surprisingly not as effective as expected in APS compared to other autoimmune diseases. Elucidation of the B cell tolerance breakdown mechanisms in APS patients may help to develop and guide the use of novel therapeutic agents that target B cells or specific immune pathway.
•The hypercoagulable state in antiphospholipid syndrome (APS) is related to pathogenic antiphospholipid antibodies (aPL).•B cells, notably through aPL production, have a central role in the pathogenesis of APS.•aPL development may result from mono/polygenic inborn errors of immunity and specific interactions with commensal hosts.•Paradoxically, B cell targeting therapies are disappointing in APS as compared to experiences in other autoimmune diseases.
Adolescence is a time of physical, psychological and social changes between childhood and adulthood. All adolescents and young adults (AYAs) are in transition and experience key underlying processes ...that will influence their later life. It is a critical period, particularly for AYAs with a chronic medical condition. Diseases can start at any point during adolescence. The transition of care will concern health care providers, as well as more unexpected actors such as social workers, teachers, business managers and the family. In this review, we focus on transition in primary immunodeficiencies (PIDs) and autoimmune diseases (AIDs). We describe the challenges and needs of transition in the field. Questions that AYAs with PID and/or AID must face during transition in their familial, professional and personal life are discussed. We expose a practical, AYA centered approach to help physicians in their daily practice, and we propose a position for the future.
•Transition of care is a critical time for youth affected with chronic immune disorders.•Transition is a continuous process starting the day of the diagnosis in childhood until adulthood.•There is a need for coordinated and personalized programmes.
Objective
Silica is an environmental substance strongly linked with autoimmunity. The aim of this study was to assess the prevalence of antineutrophil cytoplasmic antibody (ANCA)–associated ...vasculitis (AAV), including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and renal limited vasculitis, in a northeastern region of France and to evaluate whether there was a geospatial association between the localization of quarries in the region and the prevalence of these AAVs.
Methods
Potential AAV patients were identified using 3 sources: hospital records, immunology laboratories, and the French National Health Insurance System. Patients who resided in the Alsace region of France as of January 1, 2016 and who fulfilled the American College of Rheumatology criteria for GPA or the 2012 Chapel Hill Consensus Conference definitions for GPA or MPA were included. Incomplete case ascertainment was corrected using a capture–recapture analysis. The spatial association between the number of cases and the presence of quarries in each administrative entity was assessed using regression analyses weighted for geographic region.
Results
Among 910 potential AAV patients, we identified 185 patients fulfilling inclusion criteria: 120 patients with GPA, 35 patients with MPA, and 30 patients with renal limited vasculitis. The number of cases missed by any source as estimated by capture–recapture analysis was 6.4 (95% confidence interval 95% CI 3.6–11.5). Accordingly, the estimated prevalence in Alsace in 2016 was 65.5 GPA cases per million inhabitants (95% CI 47.3–93.0), 19.1 MPA cases per million inhabitants (95% CI 11.3–34.3), and 16.8 renal limited vasculitis cases per million inhabitants (95% CI 8.7–35.2). The risk of AAV was significantly increased in communities with quarries (odds ratio 2.51 95% CI 1.66–3.80), and geographic‐weighted regression analyses revealed a significant spatial association between the proximity to quarries and the number of GPA cases (P = 0.039). In analyses stratifying the AAV patients by ANCA serotype, a significant association between the presence of quarries and positivity for both proteinase 3 ANCAs (P = 0.04) and myeloperoxidase ANCAs (P = 0.03) was observed.
Conclusion
In a region with a high density of quarries, the spatial association between the presence of and proximity to quarries and the prevalence of AAVs supports the idea that silica may have a role as a specific environmental factor in this disease.
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