Specific and Polyfunctional T Cell Response Against -Methyl-d-aspartate Receptor in an Autoantibody-Mediated Encephalitis Model.

Background: Anti--Methyl-d-aspartate receptor (NMDAR) autoimmune encephalitis (NMDAR AE) is an autoimmune disease characterized by severe psychiatric and neurological symptoms. While the pathogenic role of antibodies (Abs) directed against the GluN1 subunit of NMDAR is well described in this disease, the immune mechanisms involved in the generation of the autoimmune B cell response, especially the role of T helper cells, are poorly understood. Previously, we developed a B-cell-mediated mouse model of NMDAR AE by immunization with a GluN1 peptide that drives a series of symptoms that recapitulate AE such as anxiety behaviour and spatial memory impairment.

Tissue-plasminogen activator effects on the phenotype of splenic myeloid cells in acute inflammation.

Tissue-plasminogen activator (tPA) is a serine protease well known for its fibrinolytic function. Recent studies indicate that tPA could also modulate inflammation via plasmin generation and/or by receptor mediated signalling in vitro. However, the contribution of tPA in inflammatory processes in vivo has not been fully addressed.

Disease patterns and specific trajectories of anti-MDA5-related disease: a multicentre retrospective study of 70 adult patients.

Introduction: This study aimed to provide an updated analysis of the different prognostic trajectories of patients with anti-melanoma differentiation-associated gene 5 (MDA5) antibodies.

Methods: Among a cohort of 70 patients, baseline characteristics and phenotypes, treatments and outcomes were analyzed. A Cox proportional hazards model was used to identify factors associated with poor outcomes, i.

Validation of an anti-α-Gal IgE fluoroenzyme-immunoassay for the screening of patients at risk of severe anaphylaxis to cetuximab.

Background: The link between immediate hypersensitivity reactions (HSR) following the first cetuximab infusion and the IgE sensitization against anti-galactose-α-1,3-galactose (α-Gal) is now well-established. An automated Fluoroenzyme-Immunoassay (FEIA) is available and may facilitate the screening of patients with anti-α-Gal IgE before treatment.

Methods: This study aimed to evaluate its performances as compared to a previously validated anti-cetuximab IgE ELISA, using 185 samples from two previously studied cohorts.

The diagnostic challenge of patients with anti-U1-RNP antibodies.

Anti-U1-RNP antibodies are necessary for the diagnosis of mixed connective tissue disease (MCTD), but they are also prevalent in other connective tissue diseases, especially systemic lupus erythematosus (SLE), from which distinction remains challenging. We aimed to describe the presentation and outcome of patients with anti-U1-RNP antibodies and to identify factors to distinguish MCTD from SLE. We retrospectively applied the criteria sets for MCTD, SLE, systemic sclerosis (SSc) and rheumatoid arthritis (RA) to all patients displaying anti-U1-RNP antibodies in the hospital of Caen from 2000 to 2020.

Roles of the tissue-type plasminogen activator in immune response.

The COVID-19 pandemic has once again brought to the forefront the existence of a tight link between the coagulation/fibrinolytic system and the immunologic processes. Tissue-type plasminogen activator (tPA) is a serine protease with a key role in fibrinolysis by converting plasminogen into plasmin that can finally degrade fibrin clots. tPA is released in the blood by endothelial cells and hepatocytes but is also produced by various types of immune cells including T cells and monocytes.

[The detection of antithyroid antibodies in cerebrospinal fluid using fluorescent enzyme immuno assay (FEIA) is suitable for biological diagnosis of Hashimoto's encephalopathy].

Hashimoto encephalopathy (HE) is a rare condition often underdiagnosed. The clinical picture is heterogeneous with numerous neurological signs and is associated with the presence of high levels of anti-thyroperoxidase (TPO) and / or anti-thyroglobulin (TG) antibodies in the blood and cerebrospinal fluid (CSF). The determination of anti-TPO and anti-TG antibodies in CSF is performed in only few laboratories.

Tissue plasminogen activator worsens experimental autoimmune encephalomyelitis by complementary actions on lymphoid and myeloid cell responses.

Background: Tissue plasminogen activator (tPA) is a serine protease involved in fibrinolysis. It is released by endothelial cells, but also expressed by neurons and glial cells in the central nervous system (CNS). Interestingly, this enzyme also contributes to pathological processes in the CNS such as neuroinflammation by activating microglia and increasing blood-brain barrier permeability.

Natalizumab in Multiple Sclerosis Treatment: From Biological Effects to Immune Monitoring.

Multiple sclerosis is a chronic demyelinating disease of the central nervous system (CNS) with an autoimmune component. Among the recent disease-modifying treatments available, Natalizumab, a monoclonal antibody directed against the alpha chain of the VLA-4 integrin (CD49d), is a potent inhibitor of cell migration toward the tissues including CNS. It potently reduces relapses and active brain lesions in the relapsing remitting form of the disease.

[Mechanisms of radiation-induced lymphopenia and therapeutic impact].

Radiation induced lymphopenia is frequent and can be severe and durable. Although lymphocytes have long been known as highly radiosensitive cells, it is poorly characterized. Radiation-induced lymphopenia seems to affect lymphocyte subpopulations differently and seems to be influenced by radiation modalities.

[ANCA and anti-MBG double-positive vasculitis: An update on the clinical and therapeutic specificities and comparison with the two eponymous vasculitis].

Double-positive vasculitis with anti-polynuclear cytoplasm (ANCA) and anti-glomerular basement membrane (GBM) antibodies is a rare entity of systemic vasculitis defined by the presence of ANCA and anti-GBM antibodies. The gradual accumulation of clinical and therapeutic data shows the usefulness of identifying and differentiating this entity from the two vasculitis respectively associated with the isolated presence of each of these two antibodies. Indeed, the double-positive ANCA and anti-GBM vasculitis appears to associate the characteristics of the demography and the extra-renal and pulmonary involvement of the ANCA-associated vasculitis on the one hand, and of the histological type and severe renal prognosis of the anti-MBG vasculitis on the other hand, with the renal involvement which is the only involvement consistently observed in double-positive vasculitis.

HLA-Class II Artificial Antigen Presenting Cells in CD4 T Cell-Based Immunotherapy.

CD4 T cells differentiate into various T helper subsets characterized by distinct cytokine secreting profiles that confer them effector functions adapted to a variety of infectious or endogenous threats. Regulatory CD4 T cells are another specialized subset that plays a fundamental role in the maintenance of immune tolerance to self-antigens. Manipulating effector or regulatory CD4 T cells responses is a promising immunotherapy strategy for, respectively, chronical viral infections and cancer, or severe autoimmune diseases and transplantation.

Increased frequencies of circulating and tumor-resident Vδ1 T cells in patients with diffuse large B-cell lymphoma.

Gamma-delta (γδ) T cells contribute to the innate immune response against cancer. In samples of 20 patients upon DLBCL diagnosis, we found that Vδ1 T cells were the major γδ T cell subset in tumors and PBMCs of patients, while Vδ2 T cells were preponderant in PBMCs of healthy subjects. Interestingly, the germinal center (GC) subtype was associated with an increase in Vδ1 T cells in tumors, whereas the non-GC subtype was associated with a lower frequency of γδ T cells.

In Vivo Cysteinyl Leukotriene Release in Allergic and Nonallergic Immediate Hypersensitivity Reactions during Anesthesia.

Background: Immediate hypersensitivity reactions occurring during anesthesia are classified as allergic when skin tests and mast cell tryptase are positive and as nonallergic when negative results are obtained. Cysteinyl leukotrienes (cysLTs) are potent mediators synthesized by mast cell and eosinophil that induce bronchial constriction. They could play a role in hypersensitivity reactions.

Is it relevant to screen young women hospitalized in psychiatric department for neuropsychiatric systemic lupus erythematosus (NPSLE)?: A prospective study of 100 psychiatric inpatients.

On the basis that diagnosis of neuropsychiatric systemic lupus erythematosus (NPSLE) is sometimes difficult and systemic lupus erythematosus (SLE) can present with isolated psychiatric symptoms, we initiated a survey in a psychiatric department to screen for NPSLE in young female inpatients.We prospectively studied consecutive young female patients referred to the department of psychiatry. Antinuclear antibodies (ANA), anti-deoxyribonucleic acid (DNA), and antiextractable soluble nuclear antigens (ENA) in the serum of patients were screened.

Utility of serum anti-cetuximab immunoglobulin E levels to identify patients at a high risk of severe hypersensitivity reaction to cetuximab.

Aim: Cetuximab is an anti-epidermal growth factor receptor antibody used for the treatment of metastatic colorectal cancer and head and neck cancer. Hypersensitivity reactions (HSRs) are associated with cetuximab use. The aim of the study was to evaluate the utility of anti-cetuximab immunoglobulin E (IgE) detection in order to identify patients at risk of HSR to cetuximab.

Artificial antigen-presenting cells expressing HLA class II molecules as an effective tool for amplifying human specific memory CD4(+) T cells.

Owing to their multiple immune functions, CD4(+) T cells are of major interest for immunotherapy in chronic viral infections and cancer, as well as for severe autoimmune diseases and transplantation. Therefore, standardized methods allowing rapid generation of a large number of CD4(+) T cells for adoptive immunotherapy are still awaited. We constructed stable artificial antigen-presenting cells (AAPCs) derived from mouse fibroblasts.