Evidence for spontaneous regulation of the humoral IgM anti-GM1 autoimmune response by IgG antibodies in multifocal motor neuropathy patients.

BACKGROUND AND AIMS: Multifocal motor neuropathy (MMN) is a peripheral nerve disorder characterized by slow progressive distal asymmetric weakness with minimal or no sensory impairment. Currently, a vast evidence supports a direct pathogenic role of IgM anti-GM1 antibodies on disease pathogenesis. Patients with MMN seropositive for GM1-specific IgM antibodies have significantly more weakness, disability and axon loss than patients without these antibodies. During the screening for IgM anti-GM1 antibodies in a cohort of patients with neuropathy we noticed an absence or significant reduction of natural IgM anti-GM1 autoreactivity in some patients with MMN, suggesting a mechanism of self-control of autoreactivity. We aim to understand the lack of natural reactivity against GM1 in MMN patients. METHODS: The presence of free IgM anti-GM1 reactivity or its complex to blocking IgG was analysed by combining high performance thin layer chromatography-immunostaining, soluble binding inhibition assays, Protein-G or GM1-affinity columns and dot blot assays. RESULTS: We identified in MMN patients an immunoregulation of IgM anti-GM1 antibodies mediated by IgG immunoglobulins characterized by: (i) lack of natural IgM anti-GM1 autoreactivity as a result of a immunoregulatory IgG-dependent mechanism; (ii) presence of natural and disease-associated IgM anti-GM1/IgG blocking Ab complexes in sera; and (iii) high levels of IgG blocking against natural IgM anti-GM1 antibodies (Abs. INTERPRETATION: Our observations unmask a spontaneous IgG-dependent mechanism of immunoregulation against IgM anti-GM1 antibodies that could explain, in part, fluctuations in the usually slowly progressive clinical course that characterizes the disease and, at the same time, allows the identification of an autoimmune response against GM1 ganglioside in seronegative patients.

Sialic acid and anti-ganglioside M1 antibodies are invaluable biomarkers correlated with the severity of autism spectrum disorder.

BACKGROUND: Autism spectrum disorders (ASD) are devastating neurodevelopmental disorders that showed global increased prevalence. They are characterized by impairment of social communication and stereotyped patterns. OBJECTIVE: This study aimed at measuring the levels of total sialic acid (SA) and anti-ganglioside M1 (anti- GM1) IgG antibodies as essential biomarkers in a cohort of children with ASD to identify their diagnostic yield as well as their correlation with the severity of autistic behaviors. METHODS: The demographic characteristics, anthropometric measurements, and clinical data were recorded. The levels of total plasma SA and serum anti-GM1 IgG antibodies levels were measured in 100 children with ASD and 100 healthy controls. The severity of ASD-related symptoms was assessed by using the Childhood Autism Rating Scale (CARS). RESULTS: Children with ASD had significantly higher levels of both SA and anti-GM1 antibodies than healthy controls (p < 0.001). SA showed a statistically significant moderate diagnostic performance while anti-GM1 antibody showed a statistically significant high diagnostic in differentiating severe from mild to moderate autism. Moreover, both SA and anti-GM1 antibodies levels were significantly correlated to the severity of ASD symptoms (p < 0.001). CONCLUSION: The significantly increased levels of SA and anti-GM1 antibodies in children with ASD and their correlation with autism-related symptoms suggest their possible etiopathogenic role in autism as one of the pediatric autoimmune neuropsychiatric disorders. However, further large-scale studies are still needed to explore their possible bidirectional relationship as biomarkers for autism.

[Finger drop variant of Guillain-Barré syndrome: a case report].

We report the case of a 31-year-old man with a finger drop variant of Guillain-Barré syndrome (GBS). The patient visited a neurological clinic with complaints of difficulty in extending the fingers, which occurred seven days after he had fever and diarrhea. The physician who first saw the patient suspected posterior interosseous nerve palsy and referred him to our hospital. Neurological examination 35 days after the onset revealed distal weakness of the upper extremities, particularly in the bilateral extensor digitorum (Medical Research Council [MRC] scale 1/1 [right/left]). The left triceps surae muscle was also weak (MRC scale 5/4). Bilateral Achilles tendon reflexes were absent, but other neurological findings were normal. Cerebrospinal fluid examination showed albuminocytologic dissociation. Serum immunoglobulin G antibodies against GM1 were positive. Nerve conduction studies revealed reduced amplitude of compound muscle action potentials (CMAPs) without evidence of demyelination in the median, ulnar, radial, and tibial nerves. CMAP amplitude was most severely reduced in the radial nerve among the upper extremity nerves. We diagnosed the patient with acute motor axonal neuropathy. His symptoms gradually improved after treatment with intravenous immunoglobulin. When encountering acute finger drop, neurologists should consider the finger drop variant of GBS as a differential diagnosis.

Treatment related fluctuation and response to intravenous immunoglobulin therapy in post COVID-19 Guillain-Barre syndrome.

Treatment related fluctuation (TRF) poses a special challenge in the treatment of Guillain-Barre syndrome (GBS). Many cases of GBS following COVID-19 infection have been reported in literature till date, but treatment related fluctuation (TRF) in post COVID-19 GBS has not been reported till date. We report a 35-year-old male patient who developed GBS following COVID-19 infection and had TRF after intravenous immunoglobulin (IV-IG) therapy. He required ventilator support but repeat IV-IG therapy led to complete recovery. Significant proximal muscle involvement, cranial nerve palsy, no antecedent diarrhea and absence of anti-GM1 antibodies are important predictors of TRF in GBS and need to be recognized early in the course of this illness. Early recognition of TRF and differentiating it from other forms of immune mediated neuropathy such as acute onset chronic inflammatory demyelinating polyradiculoneuropathy (A-CIDP) are important for prognostication and management.

A case of monofocal motor neuropathy with GM1 and GD1b antibodies improved with intravenous immunoglobulin.

Multifocal motor neuropathy is a purely motor neuropathy with a probably dysimmune pathogenesis, supported by the presence of anti-GM1 IgM antibodies in about half of the cases. Single nerve involvement allows for diagnosis of possible multifocal motor neuropathy. We present the case of a middle age man presenting with progressive weakness and hypotrophy in the left leg and difficulty in walking, in which we have diagnosed a dysimmune mononeuropathy. Treatment with IVIg was performed with substantial improvement. Although only one nerve is involved, early diagnosis of dysimmune mononeuropathy is important to start IVIg treatment that is often decisive.

Distal limb weakness phenotype of Guillain-Barré syndrome.

OBJECTIVE: Several regional variants of Guillain-Barré syndrome (GBS) have been proposed in western countries, but other variants remain unclear, especially among mildly disabled cases. The aim of this study was to identify unvalidated GBS phenotypes among Japanese patients with mild GBS. METHODS: Retrospective study of a cohort of patients at a University Hospital in Japan. RESULTS: Among 107 GBS patients, 25 (23%) were classified as having mild GBS (GBS disability scale ≤ 2 at nadir). A review of mild cases identified 8 patients (7.5% of all GBS and 32% of mild GBS) with an unusual phenotype, namely a distal limb weakness form of GBS (DL-GBS), which showed limited distribution of limb weakness within hands and feet with preserved strength in proximal limb muscles. The patients with DL-GBS were characterized by mild-to-moderate weakness in distal parts of limbs especially fingers, lacking or mild sensory disturbance at distal limbs, sometimes hyperreflexia at legs, and having prior Campylobacter jejuni enteritis. Among the patients with GBS after C. jejuni enteritis, DL-GBS patients were characterized by frequent detection of anti-GM1 antibodies without anti-GD1a antibodies, whereas the others were often positive for the two antibodies. CONCLUSIONS: DL-GBS is a distinct regional phenotype of GBS, which should be differentiated from cervical myelopathy. It can be generally categorized as a mild type of GBS after C. jejuni enteritis, which has characteristic pattern of anti-ganglioside autoantibodies.

Acute myelitis with positive GM1 antibodies in children: a report of two cases / 临床儿科杂志

Objective To investigate clinical characteristics and treatment of acute myelitis in children. Methods Clinical data and prognosis of two cases of pediatric acute myelitis with positive serum monosialoganglioside (GM1) antibodies were analyzed, and related literatures were reviewed. Results Two cases had clinical symptoms and MRI change of myelitis with positive serum GM1-IgM antibody and thyroid antibody. Two cases had positive serum Helicobacter pylori IgG antibody and one case has positive Mycoplasma pneumoniae IgM antibody.After treated with high doses of glucocorticoid and gamma-globulin, two cases were discharged as symptoms improved. After discharged, treatment with oral prednisone and rehabilitation were continued. One case recovered completely while another could stand alone by supporting after 3 months follow-up. Conclusion Immunologic injury played an important role in pathogenesis of acute pediatric myelitis with serum positive GM1 antibodies, which had better treatment outcome and prognosis. This type of myelitis may have intestinal Helicobacter pylori infection.

[Serum IgG antibodies to GD1a and GM1 gangliosides in elderly people].

Nowadays, the percentage of elderly people in society grows. Good nutrition and medical care help older people to have a normal life over 80 to 90 years. In the last ten years it is of critical importance to establish the clinical significance of serum IgG anti-GD1a and anti-GM1 ganglioside antibodies as potential biomarkers for neuronal damage in neurodegenerative diseases and immune-mediated neuropathies and demyelination. In the current study, the diagnostic values of IgG anti-GD1a and anti-GM1 antibodies were determined by the ELISA method in serum samples of 18 elderly patients (71-91 years). Significantly elevated serum IgG anti-GD1a and anti-GM1 antibodies titers were detected only in patients over 80 years. These data suggest that the immune-mediated neuropathies, neurodegeneration and demyelination in healthy elderly occur after 80 years old. Therefore, IgG anti-GD1a and anti-GM1 antibodies can serve as biomarkers, showing the nervous system dysfunction.

Immunoreactivity of glycoproteins isolated from human peripheral nerve and Campylobacter jejuni (O:19).

OBJECTIVE: Antibodies to ganglioside GM1 are associated with Guillain-Barré Syndrome (GBS) in patients with serologic evidence of a preceding infection with Campylobacter jejuni. Molecular mimicry between C. jejuni Lipopolysaccharide (LPS) and ganglioside GM1 has been proven to be the immunopathogenic mechanism of the disease in the axonal variant of GBS. GM1-positive sera cross-react with several Gal-GalNAc-bearing glycoproteins from the human peripheral nerve and C. jejuni (O:19). This study aimed to examine the immunoreactivity of the digested cross-reactive glycoproteins isolated from the human peripheral nerve and C. jejuni (O:19) with Peanut Agglutinin (PNA) as a marker for the Gal-GalNAc determinant, and with sera from patients with GBS. MATERIALS AND METHODS: For this purpose, the cross-reactive glycoproteins from peripheral nerve and C. jejuni (O:19) were enzymatically digested with trypsin and the obtained peptides were incubated with PNA and GBS sera. RESULTS: Western blot analysis of the separated peptides revealed several bands showing positive reactivity to PNA and to sera from patients with GBS, present in both digests from peripheral nerve and C. jejuni (O:19). CONCLUSIONS: These data indicate the possible molecular mimicry between the cross-reactive glycoproteins present in C. jejuni and human peripheral nerve and its potential role in the development of GBS following infection with C. jejuni (O:19).

Acute Motor Axonal Neuropathy Associated with Anti-GM1 Antibody: A case report

Guillain-Barre syndrme (GBS) has several subtypes that are divided by clinical, electro- physiological, and pathological findings. A novel form of GBS, that is termed acute motor axonal neuropathy (AMAN), is characterized by the selective involvement of motor fibers, and is associated with anti-GM1 antibodies. A 8-year-old male patient were developed ascending, symmetrical paralysis, and areflexia, but no sensory disturbance. Elevated titers of serum IgG anti-GM1 antibodies were detected. His thoracolumbar spine magnetic resonance imaging (MRI) revealed thickening of cauda equina and enhancement of anterior nerve roots of T12-L1 spinal level after Gd-DTPA infusion. Electrophysiological diagnosis was acute motor axonal neuropathy (AMAN). We report this case with review of the literature.