Miller Fisher syndrome is associated with serum antibodies to GQ1b ganglioside.

Abstract

A recent report described serum antiGQlb ganglioside antibodies in Miller Fisher syndrome (MFS), a clinical variant of Guillain-Barre syndrome (GBS). Four consecutive cases ofMFS all had high titre anti-GQlb antibodies which were absent from all control sera including those of patients with GBS. (i Neurol Neurosurg Psychiatry 1993;56:204-206) Antibodies directed against gangliosides are being increasingly identified in patients with a variety of acute and chronic neuropathies. ' Patients and methods All patients were diagnosed and treated in this institute and represent the consecutive cases of MFS and GBS admitted over the last 18 months. MFS was defined as a clinical syndrome comprising ataxia, areflexia and ophthalmoplegia with or without bulbar or facial muscle involvement and with clinically insignificant limb weakness. Serum samples were collected at the time of admission (as close to the onset of symptoms as possible) and stored in aliquots at -70°C until assayed. Sera from four patients with typical MFS and 20 patients with GBS were tested. Control sera comprised randomly selected patients with multiple sclerosis (n = 10), other neurological diseases including myasthenia gravis, myopathies and motor neuron disease (n = 14) and normal volunteers from the local community (n = 13).Anti-ganglioside antibody assays were performed using standard enzyme linked immunosorbent assay (ELISA) and thin layer chromatography (TLC) overlay techniques as previously described.8 Briefly, ELISAs were performed by coating microtitre trays with 100 ng purified GQlb (Novabiochem, Nottingham, UK) or 100 ng of GM1, GD1a, GDlb, GD3 and GTlb (Sigma Chemicals, Poole, UK) in 50,u1 methanol per well and evaporating to dryness. Sera were serially diluted from 1/100 in fivefold dilutions in phosphate buffered saline (PBS) containing 0-1% bovine serum albumin (BSA), pH 7*4 and incubated overnight at 4°C. CSF was assayed neat and serially diluted in twofold dilutions as necessary. After washing the plates 10 times with PBS, a 1/3000 dilution of peroxidase labelled anti-human IgM or IgG (Dako) was added and incubated for 4 hours at 4°C. Plates were developed by adding substrate solution comprising 20 mg o-phenylenediamine (Sigma) in 60 mls 0-1 M citrate buffer pH5-5 with 20 pul of 30% hydrogen peroxide.The reaction was stopped with 20,ul H2S04 after 20 minutes and the optical densities (OD) read in an MR5000 plate-reader (Dynatech). All samples were assayed in duplicate on at least two separate occasions. Both antigencoated wells and blank wells were incubated with test serum and the OD values and titres calculated after subtracting the blank well OD from the coated well OD.For the TLC overlay, gangliosides were separated on aluminium backed Kieselgel 60 WF254 S HPTLC plates (Merck) in the solvent system chloroform:methanol:0 25% KCI in a volume ratio of 50:40:10. The chromatograms were air-dried, dipped in 0 1% polyisobutylmethacrylate (PIMBS) beads for 20 seconds at 40°C, air dried, blocked with 1% BSA in PBS pH 7-5 for 1 h...

A somatically mutated human antiganglioside IgM antibody that induces experimental neuropathy in mice is encoded by the variable region heavy chain gene, V1-18.

“…MFS is an acute postinfectious autoimmune neuropathy which may follow Campylobacter jejuni (Cj) infection. MFS bears a strong clinical resemblance to the phenotype seen in the CANOMAD and over 95% of MFS cases have IgG antibodies to epitopes present on GQ1b and GT1a and other NeuAc(␣2-8)NeuAc(␣2-3)Gal configured gangliosides including GD1b, GT1b, and GD3 (53)(54)(55). It has previously been shown that both the anti-GQ1b antibodies in MFS sera and anti-GM1 antibodies in GBS sera react with carbohydrate epitopes on Cj LPS, and the model proposed for the illness is thus one of molecular mimicry in which the humoral immune response to Cj LPS fortuitously cross-reacts with neural ganglioside antigens, thereby inducing the neuropathy (7)(8)(9)(10)(11).…”

Acute oropharyngeal palsy is associated with antibodies to GQ1b and GT1a gangliosides.

“…Of these, the most widely recognised is the Miller Fisher syndrome,2 in which serum antibodies to GQlb are found in over 90% of patients. [3][4][5] Anti-GQlb antibodies are also present in patients with Guillain-Barre syndrome who exhibit ophthalmoplegia.6. These clinicoserological studies have led some authors to suggest that anti-GQlb antibodies are a marker for ophthalmoplegia.…”

Síndrome de Miller Fisher en un niño de 12 años

“…El SMF, la oftalmoparesia aguda sin ataxia (OA), la encefalitis de Bickerstaff (EB) y el SGB con oftalmoplejía, serían parte del espectro continuo de este síndrome (14). Nuestro paciente tuvo un dosaje negativo de anticuerpo anti-GQ1b, este resultado no descarta la enfermedad, ya que según los datos reportados, el anticuerpo resulta positivo solo en alrededor del 90% de los casos (15,16), además una posible explicación a este resultado negativo, sería una baja concentración de anticuerpos anti-GQ1b al momento de la toma de muestra (tercera semana de enfermedad), los cuales tiene tienen un pico al inicio de la clínica y disminuyen hasta desaparecer en unas 4-5 semanas (17).…”