A comprehensive analysis of the epidemiology and clinical characteristics of anti-LRP4 in myasthenia gravis

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Analysis of nAChR Autoantibodies Against Extracellular Epitopes in MG Patients

Myasthenia gravis (MG) is an autoimmune disorder caused by autoantibodies targeting components of the postsynaptic membrane of the neuromuscular junction (NMJ), leading to neuromuscular transmission deficiency. In the vast majority of patients, these autoantibodies target the nicotinic acetylcholine receptor (nAChR), a heteropentameric ion channel anchored to the postsynaptic membrane of the NMJ. Autoantibodies in patients with MG may target all the subunits of the receptor at both their extracellular and intracellular regions. Here, we combine immunoadsorption with a cell-based assay to examine the specificity of the patients' autoantibodies against the extracellular part of the nAChR. Our results reveal that these autoantibodies can be divided into distinct groups, based on their target, with probably different impacts on disease severity. Although our findings are based on a small sample group of patients, they strongly support that additional analysis of the specificity of the autoantibodies of patients with MG could serve as a valuable tool for the clinicians' decision on the treatment strategy to be followed. Copyright © 2022 Michail, Zouvelou, Belimezi, Haroniti, Zouridakis and Zisimopoulou

Double seronegative myasthenia gravis with anti-LRP 4 antibodies

About 10% of patients with generalized myasthenia gravis do not have detectable antibodies to acetylcholine receptor or muscle specific kinase (double seronegative myasthenia). The presence of anti-low density lipoprotein receptor-related protein 4 antibodies (LRP4 Abs) has recently been reported in variable proportion of double seronegative cases. We report the presenting characteristics of two double seronegative myasthenic patients from Greece with anti-LRP4 antibodies shortly after disease onset. The first patient, a 52-year-old male, presented with a one month history of isolated neck extensor weakness; the second patient is a 52-year-old female with three months history of ocular-bulbar-cervical myasthenic weakness. Both patients presented with mild severity and responded promptly and adequately to pyridostigmine. In the female patient thymic residual tissue was detected on CT of the mediastinum. She underwent thymectomy, and histological examination revealed follicular hyperplasia. This is the first clinical report of the presenting features of newly diagnosed myasthenia with anti-LRP4 antibodies. The clinical and therapeutic implications of the anti-LRP4 antibody positivity remain to be clarified. © 2013 Elsevier B.V.

AChR-myasthenia gravis switching to double-seropositive several years after the onset

We report an early onset AChR-myasthenia gravis (MG) with biphasic clinical course. The clinical "switch" from AChR-MG to MuSK-MG emerged 16 years after the onset and 11 years after thymectomy. MuSK antibodies were detected only by cell-based assay and only upon clinical "switch", while AChR antibodies remained positive and at high titers during the whole disease course. Although the occurrence of AChR antibodies and MuSK antibodies in the same individual is rare, the re-assessment of the antibody status, using all available assays, is advisable when there is clinical indication. © 2013 Elsevier B.V

Anti-Aquaporin-1 Autoantibodies in Patients with Neuromyelitis Optica Spectrum Disorders

Autoantibodies against aquaporin-4 (AQP4), a water channel in CNS astrocytes, are detected in ∼50-80% of patients with neuromyelitis optica spectrum disorders (NMOsd), characterized by longitudinally extensive transverse myelitis (LETM) and/or optic neuritis. Although these autoantibodies present an invaluable biomarker for NMOsd and for the differential diagnosis of multiple sclerosis (MS), diagnosis of anti-AQP4-seronegative NMOsd remains challenging. We hypothesized that seronegative NMOsd patients might have autoantibodies against aquaporin-1 (AQP1), another water channel in CNS astrocytes. We initially developed a radioimmunoprecipitation assay to search for anti-AQP1 antibodies in sera from 632 individuals. Anti-AQP1 or anti-AQP4 autoantibodies were detected in 16.7% and 12%, respectively, of 348 patients with suspected NMOsd. Anti-AQP1 specificity was confirmed by competition, protein immunoblotting and ELISA assays, whereas epitope localization was studied by immunoadsorption on intact cells expressing AQP1 and peptide mapping experiments. Most anti-AQP1 autoantibodies were of the complement-activating IgG1 subclass and the majority bound to the extracellular domain of AQP1, suggesting a possible pathogenic role. Five out of 42 MS patients had anti-AQP1 antibodies, but 2 of them also had spinal cord lesions, while the anti-AQP1 antibodies in the other 3 bound to the cytoplasmic domain of AQP1. Anti-AQP1 antibodies were not detected in 100 healthy individuals or 142 patients with non-demyelinating neuroimmune diseases. Analysis of 17 anti-AQP1+/anti-AQP4- patients with suspected NMOsd showed that 5 had NMO and 11 had LETM. 12/17 of these sera bound predominantly to the extracellular AQP1 loop-Α. Overall, we found that anti-AQP1 autoantibodies are present in a subgroup of patients with chronic demyelination in the CNS and similarities with anti-AQP4-seronegative NMOsd, offering a novel potential biomarker for CNS demyelination disorders. © 2013 Tzartos et al

Autoantibodies to aquaporin-1 in Turkish neuromyelitis optica patients with and without aquaporin-4 antibodies

29th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis / 18th Annual Conference of Rehabilitation in MS -- OCT 02-05, 2013 -- Copenhagen, DENMARKWOS: 000328751401025…European Comm Treatment & Res Multiple Sclerosi

A Rare Manifestation of Secondary Hyperparathyroidism Due to Brown Tumors: A Case Report

Maria Boudina,1 Eleana Zisimopoulou,1 Pantelitsa Rakitzi,1 Sotirios Barbanis,2 Eleni Syndouka,3 Chrysanthi Zouli,1 Aimilia Fotiadou,1 Mariana Stamati Stamati,1 Chrysanthi Balodimou,1 George Christantoniou,1 Alexandra Chrisoulidou1 1Department of Endocrinology, Theagenio Cancer Hospital, Thessaloniki, Greece; 2Department of Pathology, Theagenio Cancer Hospital, Thessaloniki, Greece; 3Department of Radiology, Theagenio Cancer Hospital, Thessaloniki, GreeceCorrespondence: Maria Boudina, Department of Endocrinology, Theagenio Cancer Hospital, Thessaloniki, Greece, Email [email protected]: Brown tumors, also known as cystic fibrosa, are rare, benign, osteolytic, fibrotic lesions of the bones that occur secondary to hyperparathyroidism. They are caused by increased osteoclastic activity leading to an abnormal bone metabolism.Case Description: Here, we present the case of a 58-year-old male, who presented with painful bony lesions, initially attributed to metastatic disease. After biochemical workout, imaging and biopsy, the nature of the lesions was revealed. We discuss the differential diagnosis and clinical management of the disease.Conclusion: Patients with brown tumors should be assessed in the differential diagnosis of bony lesions and should always be tested for hyperparathyroidism. An early diagnosis is crucial for the successful treatment of such patients.Keywords: brown tumor, hyperparathyroidism, chronic kidney disease, case repor