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Nobuhiro Yuki

Publications and source records attributed to Nobuhiro Yuki.

At least 19 recordsLinked to original sources
PubMed2007

Recognition characteristics of monoclonal antibodies that are cross-reactive with gangliosides and lipooligosaccharide from Campylobacter jejuni strains associated with Guillain-Barré and Fisher syndromes.

The enteropathogen Campylobacter jejuni has the ability to synthesize glycan structures that are similar to mammalian gangliosides within the core component of its lipooligosaccharide (LOS). Exposure to ganglioside mimics in some individuals results in the production of autoantibodies that deleteriously attack nerve surface gangliosides, precipitating the onset of Guillain-Barré and Fisher syndromes (GBS and FS). We have characterized the interaction of four monoclonal antibodies (mAbs), established by sensitization of mice with LOS isolated from GBS- and FS-associated C. jejuni strains, with chemoenzymatically synthesized gangliooligosaccharides. Surface plasmon resonance (SPR) measurements demonstrate that three of the mAbs interact specifically with derivatives corresponding to their targeted gangliosides, with dissociation constants ranging from 10 to 20 microM. Antibody binding to the gangliooligosaccharides was probed by saturation transfer difference (STD) NMR spectroscopy. STD signals, resulting from antibody/oligosaccharide interaction, were observed for each of the four mAbs. In two cases, differential saturation transfer rates to oligosaccharide resonances enabled detailed epitope mapping. The binding of GD1a-S-Phe with GB1 is characterized by close association of the immunoglobulin with sites that are distributed over several residues of the oligosaccharide. This contrasts sharply with the profile observed for the binding of both GD3-S-Phe and GT1a-S-Phe with FS1. The close antigenic contacts in these ganglioside derivatives are confined to the N-acetylmannosaminyl portion of the terminal N-acetylneuraminic acid (NeuAc) residue of the disialosyl moiety. Our characterization of FS1 provides insight, at an atomic level, into how a single antigenic determinant presented by the LOS of C. jejuni can give rise to antibodies with binding promiscuity to [alphaNeuAc-(2-8)-alphaNeuAc]-bound epitopes and demonstrates why sera from FS patients have antibodies that are often reactive with more than one disialylated ganglioside.

Animals↗
PubMed2006

Leukocyte and complement activation by GM1-specific antibodies is associated with acute motor axonal neuropathy in rabbits.

Acute motor axonal neuropathy (AMAN) in humans is associated with the presence of GM1-specific antibodies. Immunization of rabbits with GM1-containing ganglioside mixtures, purified GM1, or Campylobacter jejuni lipo-oligosaccharide exhibiting a GM1-like structure elicits GM1-specific antibodies, but axonal polyneuropathy only occurs in a subset of animals. This study aimed to dissect the molecular basis for the variable induction of AMAN in rabbits. Therefore, we analyzed the pro-inflammatory characteristics of GM1-specific antibodies in plasma samples from ganglioside-immunized rabbits with and without neurological deficits. GM1-specific plasma samples from all rabbits with AMAN were capable of activating both complement and leukocytes, in contrast to none of the plasma samples from rabbits without paralysis. Furthermore, GM1-specific IgG-mediated activation of leukocytes was detected before the onset of clinical signs. These data suggest that AMAN only occurs in rabbits that develop GM1-specific antibodies with pro-inflammatory properties.

Acute Disease↗
PubMed2006

Ganglioside-specific IgG and IgA recruit leukocyte effector functions in Guillain-Barré syndrome.

The capacity of ganglioside-specific autoantibodies to recruit leukocyte effector functions was studied. Serum samples from 87 patients with Guillain-Barré (GBS) or Miller Fisher syndrome (MFS), containing GM1-, GQ1b-, or GD1b-specific IgG or IgA, were tested for leukocyte activating capacity. Ganglioside-specific IgG antibodies generally induced leukocyte activation, irrespective of specificity. The magnitude of leukocyte degranulation correlated with GM1- and GQ1b-specific IgG titers, but not with disease severity. Finally, GM1-specific IgA activated leukocytes through the IgA receptor, FcalphaRI (CD89). Therefore, both ganglioside-specific IgG and IgA can recruit leukocyte effector functions, which may be relevant in the pathogenesis of GBS and MFS.

Adolescent↗
PubMed2006

Campylobacter coli enteritis and Guillain-Barré syndrome: no evidence of molecular mimicry and serological relationship.

Campylobacter coli was isolated from two Guillain-Barré syndrome (GBS) patients who had anti-GM1 and anti-GD1 IgG antibodies. Although both this bacteria and Campylobacter jejuni are common causes of diarrheal illness, previous studies have focused only on C. jejuni as the causal agent of GBS. To determine whether C. coli also is a causative agent, we examined the hypothesis that production of anti-ganglioside antibodies is induced by ganglioside-mimics on that bacterial lipo-oligosaccharide (LOS), as in C. jejuni-associated GBS. LOSs of both C. coli isolates had very weak reactivities with anti-GM1 and anti-GD1a IgG monoclonal antibodies, whereas those of some GBS-related C. jejuni isolates had strong reactivities. Anti-GM1 and anti-GD1a IgG antibodies from the two patients were not absorbed as much by the LOSs of their isolates as were those of GBS-related C. jejuni strains. These findings do not support the hypothesis of ganglioside mimicry on C. coli isolates' LOSs. We next made a serological assay of recent C. coli infection in 74 patients with GBS, 26 with Fisher syndrome (FS), 49 with other neurological diseases (OND), and 37 normal controls (NC) using the bacterial outer membrane protein as antigen. Eight (11%) GBS and two (8%) FS patients had two or three classes of IgG, IgM, and IgA anti-C. coli antibodies. Anti-C. jejuni IgG and IgA antibody titers were significantly higher than those of anti-C. coli (respectively, p = 0.03 and 0.01). This suggests that anti-C. coli antibodies cross-react with C. jejuni protein. We concluded that a C. coli infection was not the cause of GBS in our patients. Both isolation of a microorganism from, and the positive infectious serology of, GBS patients do not always indicate the causal agent.

Adult↗
PubMed2006

Rituximab therapy in chronic inflammatory demyelinating polyradiculoneuropathy with anti-SGPG IgM antibody.

We report a patient with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) who showed high titers of anti-sulfated glucuronyl paragloboside (SGPG) IgM antibody without M-protein in serum. The patient was resistant to corticosteroids and immunosuppressants, but after administration of rituximab, clinical symptoms improved and the patient remained in a stable state for approximately 10 months. Rituximab may be a potent therapeutic option for refractory cases of CIDP irrespective of detectable M-protein in either serum or urine.

Adult↗
PubMed2006

Severe cranial nerve involvement in a patient with monoclonal anti-MAG/SGPG IgM antibody and localized hard palate amyloidosis.

We report a patient with severe cranial polyneuropathy as well as sensory limb neuropathy. Biclonal serum IgM-kappa/IgM-lambda gammopathy was found and serum anti-myelin-associated glycoprotein (MAG)/sulfoglucuronyl paragloboside (SGPG) IgM antibody was also detected. Immunofluorescence analysis of a sural nerve biopsy specimen revealed binding of IgM and lambda-light chain on myelin sheaths. No amyloid deposition was detected in biopsied tissues except for the hard palate, suggesting that the amyloidosis was of the localized type and had no relation to the pathogenesis of cranial neuropathy. Our observations indicate that the anti-MAG/SGPG IgM antibody may be responsible for this patient's cranial polyneuropathy, which is a rare manifestation in anti-MAG/SGPG-associated neuropathy.

Amyloid↗
PubMed2006

Identification of a sialate O-acetyltransferase from Campylobacter jejuni: demonstration of direct transfer to the C-9 position of terminalalpha-2, 8-linked sialic acid.

We have identified a sialate O-acetyltransferase in the lipo-oligosaccharide biosynthesis locus of Campylobacter jejuni. Strains possessing this locus are known to produce sialylated outer core structures that mimic host gangliosides, and have been implicated in triggering the onset of Guillain-Barré syndrome. The acetyltransferase, which was cloned and expressed as a fusion construct in Escherichia coli, is soluble and homologous with members of the NodL-LacA-CysE family of O-acetyltransferases. This enzyme catalyzes the transfer of O-acetyl groups onto oligosaccharide-bound sialic acid, with a high specificity for terminal alpha2,8-linked residues. The modification is directed to C-9 and not C-7 as is believed to occur more commonly in other organisms. Despite their wide prevalence and importance in both eukaryotes and prokaryotes, this is the first report to describe the characterization of a purified sialate O-acetyltransferase.

Acetyltransferases↗
PubMed2006

Comprehensive analysis of bacterial risk factors for the development of Guillain-Barre syndrome after Campylobacter jejuni enteritis.

BACKGROUND: Guillain-Barre syndrome (GBS), a postinfectious autoimmune-mediated neuropathy, is a serious complication after Campylobacter jejuni enteritis. METHODS: To investigate the bacterial risk factors for developing GBS, genotypes, serotypes, and ganglioside mimics on lipo-oligosaccharide (LOS) were analyzed in C. jejuni strains from Japanese patients. RESULTS: Strains from patients with GBS had LOS biosynthesis locus class A more frequently (72/106; 68%) than did strains from patients with enteritis (17/103; 17%). Class A strains predominantly were serotype HS:19 and had the cstII (Thr51) genotype; the latter is responsible for biosynthesis of GM1-like and GD1a-like LOSs. Both anti-GM1 and anti-GD1a monoclonal antibodies regularly bound to class A LOSs, whereas no or either antibody bound to other LOS locus classes. Mass-spectrometric analysis showed that a class A strain carried GD1a-like LOS as well as GM1-like LOS. Logistic regression analysis showed that serotype HS:19 and the class A locus were predictive of the development of GBS. CONCLUSIONS: The high frequency of the class A locus in GBS-associated strains, which was recently reported in Europe, provides the first GBS-related C. jejuni characteristic that is common to strains from Asia and Europe. The class A locus and serotype HS:19 seem to be linked to cstII polymorphism, resulting in promotion of both GM1-like and GD1a-like structure synthesis on LOS and, consequently, an increase in the risk of producing antiganglioside autoantibodies and developing GBS.

Antibodies, Bacterial↗
PubMed2006

Isolated abducens nerve palsy as a regional variant of Guillain-Barré syndrome.

The authors reviewed clinical profiles and laboratory findings for 100 cases of abducens nerve paresis without impairment of the other cranial nerves, limb weakness, and ataxia throughout the clinical course. Review of the medical records of 9300 patients referred to our neuoroimmunological laboratory for serum anti-ganglioside antibody testing. Information was obtained from each primary physician on symptoms of preceding infection; initial symptoms; neurological signs during the illness; the clinical course; treatment provided; and outcome. Isolated abducens nerve paresis was present in 100 patients and bilateral paresis in 29. Tentative diagnoses made by the primary physicians on request of anti-ganglioside antibody testing were abducens nerve palsy (n = 68), Fisher syndrome (n = 14), acute ophthalmoparesis without ataxia (n = 14). Symptoms of infection anteceded in 63. Tendon reflexes were absent or decreased in 27. Distal paresthesias were experienced by seven. Serum anti-GQ1b antibody was positive in 25. These findings suggest that some cases of isolated abducens nerve palsy can be categorized as a regional variant of Guillain-Barré syndrome or mild form of Fisher syndrome.

Abducens Nerve↗
PubMed2006

High affinity of anti-GM1 antibodies is associated with disease onset in experimental neuropathy.

High antibody affinity has been proposed as a disease determinant factor in neuropathies associated with anti-GM1 antibodies. An experimental model of Guillain-Barré syndrome, induced by immunization of rabbits with bovine brain gangliosides or GM1, was described recently (Yuki et al. [2001] Ann. Neurol. 49:712-720). We searched plasma from these rabbits, taken at disease onset and 1 or 2 weeks prior to onset, for the presence of high-affinity anti-GM1 IgG antibodies. Affinity was estimated by soluble antigen binding inhibition. High-affinity antibodies (binding inhibition by 10(-9) M GM1) were detected at disease onset but not before. No such difference was found for other antibody parameters such as titer, fine specificity, and population distribution. These findings support the proposed role of high affinity as an important factor in disease induction by anti-GM1 antibodies.

Animals↗
PubMed2006

Electrophysiological subtypes and prognosis of childhood Guillain-Barré syndrome in Japan.

Guillain-Barré syndrome (GBS) is classified into acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor axonal neuropathy (AMAN), but little is known about the incidence of the subtypes and the prognosis of childhood GBS. To elucidate the features and long-term prognosis, clinical and electrophysiological data for 31 Japanese GBS children were reviewed. By electrodiagnostic criteria, children were classified as having AIDP (35%) or AMAN (48%), or were unclassified (16%). The AMAN children invariably had normal sensory nerve potentials. Between the two groups, age, sex, and clinical disability did not differ significantly, but the AIDP children more frequently had cranial and sensory nerve involvement, and the AMAN children more frequently had preceding gastroenteritis. By 6 months after onset, all the AIDP and 80% of the AMAN children had regained the ability to walk; by 2 years, all but one of the AMAN children could walk. In Japanese childhood GBS, the proportion of AIDP and AMAN appears to be similar. Recovery is generally favorable in both subtypes, but some of the AMAN children experienced delayed recovery.

Action Potentials↗
PubMed2006

Bacterial infections in Guillain-Barré and Fisher syndromes.

PURPOSE OF REVIEW: Progress has been made in our understanding of Guillain-Barré syndrome, especially in identifying the Campylobacter jejuni genes responsible for the development of clinical features. RECENT FINDINGS: C. jejuni is grouped into several classes based on the organization of lipo-oligosaccharide biosynthesis genes. A specific class carrying a sialyltransferase gene (cst-II) is associated with the development of Guillain-Barré syndrome, which is essential for the biosynthesis of ganglioside-like lipo-oligosaccharides. The class of C. jejuni expressed both GM1-like and GD1a-like lipo-oligosaccharides, which could induce the production of autoantibodies to GM1, to GD1a or to the GM1/GD1a complex, possibly increasing the risk of development. C. jejuni sialyltransferase (Cst-II) consists of 291 amino acids, and the 51st amino acid determines its enzymatic activity. Strains with cst-II (Thr51) expressed GM1-like or GD1a-like lipo-oligosaccharide whereas strains with cst-II (Asn51) expressed GT1a-like or GD1c-like lipo-oligosaccharide. Patients infected with the cst-II (Thr51) strains had anti-GM1 or anti-GD1a IgG antibodies, and showed limb weakness. Patients infected with the cst-II (Asn51) strains had anti-GQ1b IgG antibodies, and showed ophthalmoplegia and ataxia. SUMMARY: The cst-II gene is responsible for the development of Guillain-Barré and Fisher syndromes, and the polymorphism (Thr/Asn51) determines which syndrome develops after C. jejuni enteritis.

Animals↗
PubMed2006

Ganglioside mimicry as a cause of Guillain-Barré syndrome.

Guillain-Barré syndrome (GBS), characterized by acute progressive limb weakness and areflexia, is the prototype of postinfectious autoimmune diseases. Campylobacter jejuni is the most frequently identified agent of infection in GBS patients, often preceding acute motor axonal neuropathy (AMAN), a variant of GBS. Anti-GM1, anti-GM1b, anti-GD1a, and anti-GalNAc-GD1a IgG antibodies are associated with AMAN. Carbohydrate mimicry [Galbeta1-3GalNAcbeta1-4(NeuAcalpha2-3)Galbeta1-] was seen between the lipo-oligosaccharide of C. jejuni isolated from an AMAN patient and human GM1 ganglioside. Sensitization with the lipo-oligosaccharide of C. jejuni induces AMAN in rabbits as does sensitization with GM1 ganglioside. Paralyzed rabbits have pathological changes in their peripheral nerves identical to changes seen in human GBS. C. jejuni infection may induce anti-ganglioside antibodies by molecular mimicry, eliciting AMAN. This is the first verification of the causative mechanism of molecular mimicry in an autoimmune disease. To express ganglioside mimics, C. jejuni requires specific gene combinations that function in sialic acid biosynthesis or transfer. The knockout mutants of these landmark genes of GBS show reduced reactivity with GBS patients' sera, and fail to induce an anti-ganglioside antibody response in mice. These genes are crucial for the induction of neuropathogenic cross-reactive antibodies. An approach for evaluating intravenous immune globulin, a treatment for GBS, based on our animal model of AMAN is also discussed in this review, and recent advances made in this field are described.

Animals↗
PubMed2006

[Development of testing kits of anti-ganglioside antibody: clinical utility in Guillain-Barré and Fisher syndromes].

We developed testing kits for anti-GM1 and anti-GQ1b IgG antibodies and examined their utilities in supporting the diagnosis of Guillain-Barré syndrome (GBS) and Fisher syndrome (FS). Anti-GM1 antibody was detected in 49% of 95 patients with GBS and in 5% or less of disease and normal controls. Anti-GQ1b antibody was detected in 85% of 55 patients with FS, whereas in none of the controls. Eight GBS patients, in whom anti-GM1 IgG antibody was judged negative using the kit, were found to have other anti-ganglioside IgG antibodies. Four of them showed ophthalmoplegia and had anti-GQ1b IgG antibody. Detection of anti-GM1 IgG antibody in GBS and of anti-GQ1b IgG antibody in FS within one week after the disease onset were significantly more frequent compared to albuminocytologic dissociation in the cerebrospinal fluids (GBS, 58% vs 32%; FS, 89% vs 20%). These findings indicate that our testing kits are useful for supporting the early diagnosis of GBS and FS.

Adult↗
PubMed2005

Immunoglobulin KM allotypes are associated with the prevalence of autoantibodies to GD1a ganglioside, but not with susceptibility to the disease, in Japanese patients with Guillain-Barré syndrome.

Guillain-Barré syndrome (GBS), an autoimmune disease of the peripheral nervous system, is associated with antecedent Campylobacter jejuni infection. GM and KM allotypes--genetic markers of immunoglobulin gamma and kappa chains, respectively--are implicated in the etiopathogenesis of several autoimmune diseases. To determine if GM/KM phenotypes are associated with GBS and influence antibody responses to C. jejuni and to GM1 and GD1a gangliosides, 72 Japanese GBS patients and 73 controls were allotyped for several GM and KM markers. Sera from patients were characterized for antibodies to C. jejuni, GM1, and GD1a. The distribution of KM phenotypes was significantly different in patients with anti-GD1a ganglioside antibodies from those who lacked these antibodies (P=0.029). No other significant associations were found. These results suggest that KM allotypes are not risk factors for developing GBS, but contribute significantly to the generation of autoimmune responses to GD1a ganglioside in patients with this disease.

Campylobacter Infections↗
PubMed2005

Carbohydrate mimicry: a new paradigm of autoimmune diseases.

Molecular mimicry of microbial components by self components is thought to be the mechanism that accounts for the antigen and tissue specificity of immune responses in post-infectious autoimmune diseases. Little direct evidence exists, and research in this area has focused principally on T cell mediated anti-peptide responses, rather than on humoral responses to carbohydrate structures. Guillain-Barré syndrome, the most frequent cause of acute neuromuscular paralysis, sometimes occurs after Campylobacter jejuni enteritis. Recent studies have revealed that carbohydrate mimicry of the bacterial lipo-oligosaccharide by the human ganglioside is an important cause of the syndrome. This new concept that carbohydrate mimicry can cause an autoimmune disease provides a clue to inducing the resolution of pathogenesis of other immune-mediated diseases.

Animals↗
PubMed2005

Overexpression of GD1a ganglioside sensitizes motor nerve terminals to anti-GD1a antibody-mediated injury in a model of acute motor axonal neuropathy.

Anti-GD1a ganglioside antibodies (Abs) are the serological hallmark of the acute motor axonal form of the post-infectious paralysis, Guillain-Barre syndrome. Development of a disease model in mice has been impeded by the weak immunogenicity of gangliosides and the apparent resistance of GD1a-containing neural membranes to anti-GD1a antibody-mediated injury. Here we used mice with altered ganglioside biosynthesis to generate such a model at motor nerve terminals. First, we bypassed immunological tolerance by immunizing GD1a-deficient, beta-1,4-N-acetylgalactosaminyl transferase knock-out mice with GD1a ganglioside-mimicking antigens from Campylobacter jejuni and generated high-titer anti-GD1a antisera and complement fixing monoclonal Abs (mAbs). Next, we exposed ex vivo nerve-muscle preparations from GD1a-overexpressing, GD3 synthase knock-out mice to the anti-GD1a mAbs in the presence of a source of complement and investigated morphological and electrophysiological damage. Dense antibody and complement deposits were observed only over presynaptic motor axons, accompanied by severe ultrastructural damage and electrophysiological blockade of motor nerve terminal function. Perisynaptic Schwann cells and postsynaptic membranes were unaffected. In contrast, normal mice were not only unresponsive to immunization with GD1a but also resistant to neural injury during anti-GD1a Ab exposure, demonstrating the central role of membrane antigen density in modulating both immune tolerance to GD1a and axonal susceptibility to anti-GD1a Abmediated injury. Identical paralyzing effects were observed when testing mouse and human anti-GD1a-positive sera. These data indicate that anti-GD1a Abs arise via molecular mimicry and are likely to be clinically relevant in injuring peripheral nerve axonal membranes containing sufficiently high levels of GD1a.

Animals↗