A5004482169- Myasthenia Gravis and Thymoma
- Peripheral Neuropathies and Disorders
- Monoclonal and Polyclonal Antibodies Research
- Adrenal Hormones and Disorders
- T-cell and B-cell Immunology
- CAR-T cell therapy research
- Antifungal resistance and susceptibility
- Immunotherapy and Immune Responses
- Cancer Treatment and Pharmacology
- Immune Cell Function and Interaction
- Diabetes and associated disorders
- Autoimmune Neurological Disorders and Treatments
- Salivary Gland Tumors Diagnosis and Treatment
- Immunodeficiency and Autoimmune Disorders
- Parkinson's Disease and Spinal Disorders
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Hormonal Regulation and Hypertension
- Pituitary Gland Disorders and Treatments
- Cytomegalovirus and herpesvirus research
- Chemokine receptors and signaling
- Multiple Myeloma Research and Treatments
- Galectins and Cancer Biology
- Complement system in diseases
- Neuroblastoma Research and Treatments
- Platelet Disorders and Treatments
University College London
1981-2025
MRC Weatherall Institute of Molecular Medicine
2011-2025
The Royal Free Hospital
1981-2025
University of Oxford
2011-2024
Charité - Universitätsmedizin Berlin
2024
University Hospital Münster
2024
John Radcliffe Hospital
2002-2021
The Francis Crick Institute
2021
Hospital de Santo António
2019
University of Göttingen
2019
Chronic mucocutaneous candidiasis (CMC) is frequently associated with T cell immunodeficiencies. Specifically, the proinflammatory IL-17A–producing Th17 subset implicated in protection against fungi at epithelial surfaces. In autoimmune polyendocrinopathy ectodermal dystrophy (APECED, or polyendocrine syndrome 1), CMC often first sign, but underlying immunodeficiency a long-standing puzzle. contrast, subsequent endocrine features are clearly autoimmune, resulting from defects thymic...
Only around 80% of patients with generalized myasthenia gravis (MG) have serum antibodies to acetylcholine receptor [AChR; antibody positive (AChR-MG)] by the radioimmunoprecipitation assay used worldwide. Antibodies muscle specific kinase [MuSK; MuSK (MuSK-MG)] make up a variable proportion remaining 20%. The neither AChR nor are often called seronegative (seronegative MG, SNMG). There is accumulating evidence that SNMG similar AChR-MG in clinical features and thymic pathology. We...
The autoimmune regulator (AIRE) gene influences thymic self-tolerance induction. In polyendocrinopathy syndrome type 1 (APS1; OMIM 240300), recessive AIRE mutations lead to autoimmunity targetting endocrine and other epithelial tissues, although chronic candidiasis usually appears first. Autoimmunity can associate with thymomas as well. Patients these tumours frequently also have high titre immunoglobulin G autoantibodies neutralising I interferon (IFN)-alpha IFN-omega, which are secreted...
Dendritic cells (DC) are crucial for the induction of immune responses and thus an inviting target modulation by pathogens. We have previously shown that Plasmodium falciparum -infected erythrocytes inhibit maturation DCs. Intact P. can bind directly to CD36 indirectly CD51. It is striking these receptors, at least in part, also mediate phagocytosis apoptotic cells. Here we show antibodies against or CD51, as well exposure early cells, profoundly modulate DC function response inflammatory...
In generalized myasthenia gravis (MG) patients without detectable acetylcholine receptor (AChR) antibodies (SNMG), the thymus is often reported as "normally involuted." We analyzed thymic compartments in 67 with MG, AChR (AChR+, n = 23), muscle-specific kinase (MuSK) (MuSK+, 14) or neither (MuSK-, 30), and 11 non-MG controls. Four of 14 MuSK+ thymi had rare small germinal centers, but overall they were not different from age-matched However, approximately 75% MuSK- samples showed lymph...
In autoimmune polyendocrinopathy syndrome type I (APS-I), mutations in the regulator gene (AIRE) impair thymic self-tolerance induction developing T cells. The ensuing autoimmunity particularly targets ectodermal and endocrine tissues, but chronic candidiasis usually comes first. We recently reported apparently APS-I-specific high-titer neutralizing autoantibodies against interferons 100% of Finnish Norwegian patients, mainly with two prevalent AIRE truncations.Because variability clinical...
SUMMARY We have screened for spontaneous anticytokine autoantibodies in patients with infections, neoplasms and autoimmune diseases, because of their increasingly reported co-occurrence. tested both binding neutralizing to a range human cytokines, including interleukin-1alpha (IL-1α), IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-18, interferon-alpha2 (IFN-α2), IFN-ω, IFN-β, IFN-γ, tumour necrosis factor alpha (TNF-α), transforming growth beta-1 (TGF-β1) granulocyte-macrophage colony...
Approximately one half of patients with Lambert-Eaton myasthenic syndrome (LEMS) have small-cell lung carcinomas (SCLC), aggressive tumors poor prognosis. In view its profound impact on therapy and survival, we developed validated a score to identify the presence SCLC early in course LEMS.We derived prediction for LEMS nationwide cohort 107 Dutch patients, it similar 112 British patients. A Dutch-English Tumor Association Prediction (DELTA-P) was based multivariate logistic regression.Age at...
Autoimmune polyendocrine syndrome type 1 (APS1) is a childhood-onset monogenic disorder caused by mutations in the autoimmune regulator (AIRE) gene, including distinctive R139X Sardinia. Its rarity and great variability manifestations/onset ages make early diagnosis difficult. To date, very few longitudinal studies of APS1 patients have been reported. The aim this study was to describe features clinical course correlate them with AIRE HLA class II genotypes large homogeneous cohort Sardinian...
Abstract The muscle weakness in myasthenia gravis (MG) is mediated by autoantibodies against the nicotinic acetylcholine receptor (AChR) at neuromuscular junction. Production of these pathogenic believed to be associated with germinal centers (GC) and anti-AChR-secreting plasma cells hyperplastic thymus patients early onset MG (EOMG). Here, we describe repertoire rearranged heavy chain V genes their clonal origins GC from a typical EOMG patient. Three hundred fifteen Ig VH were amplified,...
Abstract We compared T‐cell proliferative responses to acetylcholine receptor (AChR) and purified protein derivative (PPD) (of tuberculin) of hyperplastic thymus, thymoma, blood cells from patients with myasthenia gravis (MG). Hyperplastic MG thymus gave significantly higher more consistent AChR than parallel cultures autologous cells, whereas PPD showed an opposite trend. Thus there was a preferential localization AChR‐‐reactive T in the thymus. Furthermore, strong correlation between cell...
Thymomas are thymic epithelial neoplasms, associated with a variety of autoimmune disorders (especially myasthenia gravis), that apparently result from aberrant intra-tumourous thymopoiesis and export inefficiently tolerized T-cells to the periphery. The regulator (AIRE) drives expression self-antigens in medulla plays an essential role 'central' tolerance both humans mice. However, while inactivating AIRE mutations 'autoimmune polyendocrinopathy syndrome type 1' (APS-1), its major features...
Neutralizing autoantibodies to type I, but not II, interferons (IFNs) are found at high titers in almost every patient with autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED), a disease caused by AIRE gene mutations that lead defects thymic T-cell selection. Combining genome-wide expression array real time RT-PCR assays, we here demonstrate antibodies against IFN-alpha cause highly significant down-regulation of interferon-stimulated cells from APECED patients' blood...
We investigated the role of thymus in 16 patients with myasthenia gravis without thymoma by studying production anti-acetylcholine-receptor antibody thymic and blood lymphocytes cultured alone or together. In 19 responders (with highest receptor-antibody titers their plasma), cells spontaneously produced measurable receptor antibody. Receptor-antibody autologous was enhanced addition responders' cells, irradiated to abrogate suppression (P less than 0.01). This enhancement greater more...