Muscle and Muscle-like Autoantigen Expression in Myasthenia Gravis Thymus: Possible Molecular Hint for Autosensitization.

The thymus is widely recognized as an immunological niche where autoimmunity against the acetylcholine receptor (AChR) develops in myasthenia gravis (MG) patients, who mostly present thymic hyperplasia and thymoma. Thymoma-associated MG is frequently characterized by autoantibodies to the muscular ryanodine receptor 1 (RYR1) and titin (TTN), along with anti-AChR antibodies. By real-time PCR, we analyzed muscle-CHRNA1, RYR1, and TTN-and muscle-like-NEFM, RYR3 and HSP60-autoantigen gene expression in MG thymuses with hyperplasia and thymoma, normal thymuses and non-MG thymomas, to check for molecular changes potentially leading to an altered antigen presentation and autoreactivity.

Immunological and Structural Characterization of Titin Main Immunogenic Region; I110 Domain Is the Target of Titin Antibodies in Myasthenia Gravis.

Myasthenia gravis (MG) is an autoimmune disease caused by antibodies targeting the neuromuscular junction (NJ) of skeletal muscles. The major MG autoantigen is nicotinic acetylcholine receptor. Other autoantigens at the NJ include MuSK, LRP4 and agrin.

Circulating MyomiRs as Potential Biomarkers to Monitor Response to Nusinersen in Pediatric SMA Patients.

Spinal muscular atrophy (SMA) is an autosomal recessive disorder caused by mutations in survival motor neuron (SMN) 1 gene, resulting in a truncated SMN protein responsible for degeneration of brain stem and spinal motor neurons. The paralogous SMN2 gene partially compensates full-length SMN protein production, mitigating the phenotype. Antisense oligonucleotide nusinersen (Spinraza) enhances SMN2 gene expression.

Diagnostics of anti-MAG antibody polyneuropathy.

This document presents the guidelines for anti-myelin-associated glycoprotein (MAG) antibody testing that have been developed following a consensus process built on questionnaire-based surveys, internet contacts, and discussions at workshops of sponsoring Italian Association of Neuroimmunology (AINI) congresses. The main clinical information on anti-MAG antibody polyneuropathy, indications and limits of anti-MAG antibody testing, instructions for result interpretation, and an agreed laboratory protocol (Appendix) are reported for the communicative community of neurologists and clinical pathologists.

Diagnostics of dysimmune peripheral neuropathies.

This document presents the guidelines for anti-ganglioside antibody testing that have been developed following a consensus process built on questionnaire-based surveys, internet contacts, and discussions at workshops of the sponsoring Italian Association of Neuroimmunology (AINI) congresses. Main clinical information on dysimmune peripheral neuropathies, indications and limits of anti-ganglioside antibody testing, instructions for result interpretation, and an agreed laboratory protocol (Appendix) are reported for the communicative community of neurologists and clinical pathologists.

Diagnostics of autoimmune encephalitis associated with antibodies against neuronal surface antigens.

This document presents the guidelines for testing antibodies against neuronal surface antigens that have been developed following a consensus process built on questionnaire-based surveys, internet contacts, and discussions at workshops of the sponsoring Italian Association of Neuroimmunology (AINI) congresses. Essential clinical information on autoimmune encephalitis associated with antibodies against neuronal surface antigens, indications and limits of testing for such antibodies, instructions for result interpretation, and an agreed laboratory protocol (Appendix A) are reported for the communicative community of neurologists and clinical pathologists.

Anti-MOG autoantibodies in Italian multiple sclerosis patients: specificity, sensitivity and clinical association.

There is considerable evidence that multiple sclerosis (MS) is an immune-mediated disease characterized by infiltration of inflammatory cells into the CNS and demyelination. Several myelin proteins may be encephalitogenic, including myelin basic protein, proteolipid protein and myelin oligodendrocyte glycoprotein (MOG), the latter being expressed on the external layer of myelin sheaths and hence accessible to antibody attack. We investigated MOG autoreactivity in serum and cerebrospinal fluid (CSF) by ELISA, employing the recombinant extracellular domain of MOG as antigen.

Myasthenia gravis (MG): epidemiological data and prognostic factors.

Data from 756 myasthenic patients were analyzed for diagnostic criteria, clinical aspects, and therapeutic approaches. The patients were followed up at our institution from 1981 to 2001. Clinical evaluation was performed according to the myasthenia gravis score adopted at our clinic.

Acetylcholine receptor alpha-subunit isoforms are differentially expressed in thymuses from myasthenic patients.

A central role of the thymus in autosensitization to the acetylcholine receptor has been proposed to explain the immunopathogenetic processes in myasthenia gravis (MG). Two isoforms of the alpha-subunit of the acetylcholine receptor are known; they differ by a 25-amino-acid insertion coded by the P3A exon. We investigated the expression of the P3A exon by RNA polymerase chain reaction in fetal and adult human myoblasts and TE671 cells; both isoforms were expressed.

Removal of antiacetylcholine receptor antibodies by protein-A immunoadsorption in myasthenia gravis.

Myasthenia Gravis is an autoimmune disease in which autoantibodies to the acetylcholine receptor interfere with neuromuscular transmission. Plasma exchange is effective in temporarily relieving the symptoms of the disease, but for repeated use the lack of selectivity and need for replacement fluids (which increases the risk of contracting viral diseases) are important drawbacks. Staphylococcal protein A, a potent ligand for immunoglobulins, that interacts negligibly with other plasma proteins, appears to be an optimal candidate for removing antiacetylcholine receptor antibodies, which are mostly IgG.

Immune activation in myasthenia gravis: soluble interleukin-2 receptor, interferon-gamma and tumor necrosis factor-alpha levels in patients' serum.

Soluble interleukin-2 receptor (sIL-2R), interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) levels were evaluated in serum from patients affected by myasthenia gravis (MG). sIL-2R titers were significantly increased in generalized and bulbar MG patients while ocular cases were not different from controls. Patients showing a recent clinical worsening had significantly higher sIL-2R titers when compared to the whole MG population.

Analysis of T cell receptor repertoire of muscle-infiltrating T lymphocytes in polymyositis. Restricted V alpha/beta rearrangements may indicate antigen-driven selection.

Polymyositis is an inflammatory myopathy characterized by mononuclear cell infiltration of muscle tissue. Myocytotoxic T lymphocytes have been recognized in the infiltrates, but the muscle antigen, target of the immune attack, has not been identified. Molecular characterization of the variable regions of T cell receptors (TCRs) on the infiltrating lymphocytes can be expected to provide insights into the pathogenic process.