Pablo H H Lopez

Johns Hopkins University, Baltimore, MD, United States

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Publications (27)119.07 Total impact

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    ABSTRACT: Gangliosides-sialylated glycosphingolipids-are the major glycoconjugates of nerve cells. The same four structures-GM1, GD1a, GD1b and GT1b-comprise the great majority of gangliosides in mammalian brains. They share a common tetrasaccharide core (Galβ1-3GalNAcβ1-4Galβ1-4Glcβ1-1'Cer) with one or two sialic acids on the internal galactose and zero (GM1 and GD1b) or one (GD1a and GT1b) α2-3-linked sialic acid on the terminal galactose. Whereas the genes responsible for the sialylation of the internal galactose are known, those responsible for terminal sialylation have not been established in vivo. We report that St3gal2 and St3gal3 are responsible for nearly all the terminal sialylation of brain gangliosides in the mouse. When brain ganglioside expression was analyzed in adult St3gal1-, St3gal2-, St3gal3- and St3gal4-null mice, only St3gal2-null mice differed significantly from wild type, expressing half the normal amount of GD1a and GT1b. St3gal1/2-double-null mice were no different than St3gal2-single-null mice; however, St3gal2/3-double-null mice were >95% depleted in gangliosides GD1a and GT1b. Total ganglioside expression (lipid-bound sialic acid) in the brains of St3gal2/3-double-null mice was equivalent to that in wild-type mice, whereas total protein sialylation was reduced by half. St3gal2/3-double-null mice were small, weak and short lived. They were half the weight of wild-type mice at weaning and displayed early hindlimb dysreflexia. We conclude that the St3gal2 and St3gal3 gene products (ST3Gal-II and ST3Gal-III sialyltransferases) are largely responsible for ganglioside terminal α2-3 sialylation in the brain, synthesizing the major brain gangliosides GD1a and GT1b.
    Glycobiology 06/2012; 22(10):1289-301. · 3.54 Impact Factor
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    ABSTRACT: Tumors often display mechanisms to avoid or suppress immune recognition. One such mechanism is the shedding of gangliosides into the local tumor microenvironment, and a high concentration of circulating gangliosides is associated with poor prognosis. In this study, we identify ganglioside GD3, which was isolated from the polar lipid fraction of ovarian cancer-associated ascites, as an inhibitory factor that prevents innate immune activation of natural killer T (NKT) cells. Purified GD3 displayed a high affinity for both human and mouse CD1d, a molecule involved in the presentation of lipid antigens to T cells. Purified GD3, as well as substances within the ascites, bound to the CD1d antigenic-binding site and did not require additional processing for its inhibitory effect on NKT cells. Importantly, in vivo administration of GD3 inhibited α-galactosylceramide (α-GalCer)-induced NKT cell activation in a dose-dependent manner. These data therefore indicate that ovarian cancer tumors may use GD3 to inhibit the antitumor NKT cell response as an early mechanism of tumor immune evasion.
    Cancer Research 05/2012; 72(15):3744-52. · 9.28 Impact Factor
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    ABSTRACT: In addition to supporting rapid nerve conduction, myelination nurtures and stabilizes axons and protects them from acute toxic insults. One myelin molecule that protects and sustains axons is myelin-associated glycoprotein (MAG). MAG is expressed on the innermost wrap of myelin, apposed to the axon surface, where it interacts with axonal receptors that reside in lateral membrane domains including gangliosides, the glycosylphosphatidylinositol-anchored Nogo receptors, and β1-integrin. We report here that MAG protection extends beyond the axon to the neurons from which those axons emanate, protecting them from excitotoxicity. Compared to wild type mice, Mag-null mice displayed markedly increased seizure activity in response to intraperitoneal injection of kainic acid, an excitotoxic glutamate receptor agonist. Mag-null mice also had larger lesion volumes in response to intrastriatal injection of the excitotoxin NMDA. Prior injection of a soluble form of MAG partially protected Mag-null mice from NMDA-induced lesions. Hippocampal neurons plated on proteins extracted from wild-type rat or mouse myelin were resistant to kainic acid-induced excitotoxicity, whereas neurons plated on proteins from Mag-null myelin were not. Protection was reversed by anti-MAG antibody and replicated by addition of soluble MAG. MAG-mediated protection from excitotoxicity was dependent on Nogo receptors and β1-integrin. We conclude that MAG engages membrane-domain resident neuronal receptors to protect neurons from excitotoxicity, and that soluble MAG mitigates excitotoxic damage in vivo.
    Journal of Neurochemistry 03/2011; 116(5):900-8. · 3.97 Impact Factor
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    ABSTRACT: Anti-ganglioside antibodies (Abs) are strongly associated with axonal forms of Guillain Barré syndrome (GBS). Some studies indicate that these Abs, including those with GD1a reactivity, are associated with poor prognosis and/or incomplete recovery. We recently demonstrated that a disease-relevant anti-ganglioside Ab with GD1a reactivity inhibits axon regeneration after PNS injury in an animal model (Lehmann et al., 2007). An implication of these findings is that anti-GD1a Abs can mediate inhibition of axon regeneration and limit recovery in some patients with GBS. The downstream inhibitory intracellular signaling that mediates anti-ganglioside Ab-induced axon inhibition remains unclear. In the current study, we show that disease-relevant and GBS patient's anti-ganglioside Abs can inhibit neurite outgrowth in dissociated primary neuronal cultures. Activation of small GTPase RhoA and its key downstream effector Rho kinase (ROCK) are critical mediators of growth cone and neurite outgrowth inhibition. Therefore, we examined the role of these intracellular signaling molecules in our primary neuronal cultures by molecular and pharmacologic approaches. Our results show that the Ab-mediated inhibition of neurite outgrowth involves the activation of RhoA and ROCK pathway and this activation is through the engagement of specific cell-surface gangliosides by Abs. In summary, these studies directly link patient autoantibodies to an intracellular inhibitory signaling pathway involved in anti-ganglioside Ab-mediated inhibition of neurite outgrowth.
    Journal of Neuroscience 02/2011; 31(5):1664-75. · 6.91 Impact Factor
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    ABSTRACT: Anti-GM1 antibodies are present in some patients with autoimmune neurological disorders. These antibodies are most frequently associated with acute immune neuropathy called Guillain-Barré syndrome (GBS). Some clinical studies associate the presence of these antibodies with poor recovery in GBS. The patients with incomplete recovery have failure of nerve repair, particularly axon regeneration. Our previous work indicates that monoclonal antibodies can inhibit axon regeneration by engaging cell surface gangliosides (Lehmann et al., 2007). We asked whether passive transfer of human anti-GM1 antibodies from patients with GBS modulate axon regeneration in an animal model. Human anti-GM1 antibodies were compared with other GM1 ligands, cholera toxin B subunit and a monoclonal anti-GM1 antibody. Our results show that patient derived anti-GM1 antibodies and cholera toxin beta subunit impair axon regeneration/repair after PNS injury in mice. Comparative studies indicated that the antibody/ligand-mediated inhibition of axon regeneration is dependent on antibody/ligand characteristics such as affinity-avidity and fine specificity. These data indicate that circulating immune effectors such as human autoantibodies, which are exogenous to the nervous system, can modulate axon regeneration/nerve repair in autoimmune neurological disorders such as GBS.
    Journal of Neuroscience 07/2010; 30(28):9533-41. · 6.91 Impact Factor
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    Ronald L. Schnaar, Pablo H.H. Lopez
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    ABSTRACT: Myelin-associated glycoprotein (MAG) is expressed on the innermost myelin membrane wrap, directly apposed to the axon surface. Although it is not required for myelination, MAG enhances long-term axon–myelin stability, helps to structure nodes of Ranvier, and regulates the axon cytoskeleton. In addition to its role in axon–myelin stabilization, MAG inhibits axon regeneration after injury; MAG and a discrete set of other molecules on residual myelin membranes at injury sites actively signal axons to halt elongation. Both the stabilizing and the axon outgrowth inhibitory effects of MAG are mediated by complementary MAG receptors on the axon surface. Two MAG receptor families have been described, sialoglycans (specifically gangliosides GD1a and GT1b) and Nogo receptors (NgRs). Controversies remain about which receptor(s) mediates which of MAG's biological effects. Here we review the findings and challenges in associating MAG's biological effects with specific receptors. © 2009 Wiley-Liss, Inc.
    Journal of Neuroscience Research 11/2009; 87(15):3267 - 3276. · 2.97 Impact Factor
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    Pablo H H Lopez, Ronald L Schnaar
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    ABSTRACT: Gangliosides, sialic acid-bearing glycosphingolipids, are expressed on all vertebrate cells, and are the major glycans on nerve cells. They are anchored to the plasma membrane through their ceramide lipids with their varied glycans extending into the extracellular space. Through sugar-specific interactions with glycan-binding proteins on apposing cells, gangliosides function as receptors in cell-cell recognition, regulating natural killer cell cytotoxicity via Siglec-7, myelin-axon interactions via Siglec-4 (myelin-associated glycoprotein), and inflammation via E-selectin. Gangliosides also interact laterally in their own membranes, regulating the responsiveness of signaling proteins including the insulin, epidermal growth factor, and vascular endothelial growth factor receptors. In these ways, gangliosides act as regulatory elements in the immune system, in the nervous system, in metabolic regulation, and in cancer progression.
    Current Opinion in Structural Biology 08/2009; 19(5):549-57. · 8.74 Impact Factor
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    ABSTRACT: The acute motor axonal neuropathy (AMAN) variant of Guillain-Barré syndrome (GBS) is associated with anti-GD1a and anti-GM1 IgG antibodies. The basis of preferential motor nerve injury in this disease is not clear, however, because biochemical studies demonstrate that sensory and motor nerves express similar quantities of GD1a and GM1 gangliosides. To elucidate the pathophysiology of AMAN, we have developed several monoclonal antibodies (mAbs) with GD1a reactivity and reported that one mAb, GD1a-1, preferentially stained motor axons in human and rodent nerves. To understand the basis of this preferential motor axon staining, several derivatives of GD1a were generated by various chemical modifications of N-acetylneuraminic (sialic) acid residues (GD1a NeuAc 1-amide, GD1a NeuAc ethyl ester, GD1a NeuAc 1-alcohol, GD1a NeuAc 1-methyl ester, GD1a NeuAc 7-alcohol, GD1a NeuAc 7-aldehyde) on this ganglioside. Binding of anti-GD1a mAbs and AMAN sera with anti-GD1a Abs to these derivatives was examined. Our results indicate that mAbs with selective motor axon staining had a distinct pattern of reactivity with GD1a-derivatives compared to mAbs that stain both motor and sensory axons. The fine specificity of the anti-GD1a antibodies determines their motor selectivity, which was validated by cloning a new mAb (GD1a-E6) with a chemical and immunocytochemical binding pattern similar to that of GD1a-1 but with two orders of magnitude higher affinity. Control studies indicate that selective binding of mAbs to motor nerves is not due to differences in antibody affinity or ceramide structural specificity. Since GD1a-reactive mAb with preferential motor axon staining showed similar binding to sensory- and motor nerve-derived GD1a in a solid phase assay, we generated computer models of GD1a based on binding patterns of different GD1a-reactive mAbs to different GD1a-derivatives. These modelling studies suggest that critical GD1a epitopes recognized by mAbs are differentially expressed in motor and sensory nerves. The GD1a-derivative binding patterns of AMAN sera resembled those with motor-specific mAbs. On the basis of these findings we postulate that both the fine specificity and ganglioside orientation/exposure in the tissues contribute to target recognition by anti-ganglioside antibodies and this observation provides one explanation for preferential motor axon injury in AMAN.
    Brain 06/2008; 131(Pt 7):1926-39. · 10.23 Impact Factor
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    ABSTRACT: In the injured nervous system, myelin-associated glycoprotein (MAG) on residual myelin binds to receptors on axons, inhibits axon outgrowth, and limits functional recovery. Conflicting reports identify gangliosides (GD1a and GT1b) and glycosylphosphatidylinositol-anchored Nogo receptors (NgRs) as exclusive axonal receptors for MAG. We used enzymes and pharmacological agents to distinguish the relative roles of gangliosides and NgRs in MAG-mediated inhibition of neurite outgrowth from three nerve cell types, dorsal root ganglion neurons (DRGNs), cerebellar granule neurons (CGNs), and hippocampal neurons. Primary rat neurons were cultured on control substrata and substrata adsorbed with full-length native MAG extracted from purified myelin. The receptors responsible for MAG inhibition of neurite outgrowth varied with nerve cell type. In DRGNs, most of the MAG inhibition was via NgRs, evidenced by reversal of inhibition by phosphatidylinositol-specific phospholipase C (PI-PLC), which cleaves glycosylphosphatidylinositol anchors, or by NEP1-40, a peptide inhibitor of NgR. A smaller percentage of MAG inhibition of DRGN outgrowth was via gangliosides, evidenced by partial reversal by addition of sialidase to cleave GD1a and GT1b or by P4, an inhibitor of ganglioside biosynthesis. Combining either PI-PLC and sialidase or NEP1-40 and P4 was additive. In contrast to DRGNs, in CGNs MAG inhibition was exclusively via gangliosides, whereas inhibition of hippocampal neuron outgrowth was mostly reversed by sialidase or P4 and only modestly reversed by PI-PLC or NEP1-40 in a non-additive fashion. A soluble proteolytic fragment of native MAG, dMAG, also inhibited neurite outgrowth. In DRGNs, dMAG inhibition was exclusively NgR-dependent, whereas in CGNs it was exclusively ganglioside-dependent. An inhibitor of Rho kinase reversed MAG-mediated inhibition in all nerve cells, whereas a peptide inhibitor of the transducer p75(NTR) had cell-specific effects quantitatively similar to NgR blockers. Our data indicate that MAG inhibits axon outgrowth via two independent receptors, gangliosides and NgRs.
    Journal of Biological Chemistry 10/2007; 282(38):27875-86. · 4.65 Impact Factor
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    ABSTRACT: Recent studies have proposed that neurite outgrowth is influenced by specific nerve cell surface gangliosides, which are sialic acid-containing glycosphingolipids highly enriched in the mammalian nervous system. For example, the endogenous lectin, myelin-associated glycoprotein (MAG), is reported to bind to axonal gangliosides (GD1a and GT1b) to inhibit neurite outgrowth. Clustering of gangliosides in the absence of inhibitors such as MAG is also shown to inhibit neurite outgrowth in culture. In some human autoimmune PNS and CNS disorders, autoantibodies against GD1a or other gangliosides are implicated in pathophysiology. Because of neurobiological and clinical relevance, we asked whether anti-GD1a antibodies inhibit regeneration of injured axons in vivo. Passive transfer of anti-GD1a antibody severely inhibited axon regeneration after PNS injury in mice. In mutant mice with altered ganglioside or complement expression, inhibition by antibodies was mediated directly through GD1a and was independent of complement-induced cytolytic injury. The impaired regenerative responses and ultrastructure of injured peripheral axons mimicked the abortive regeneration typically seen after CNS injury. These data demonstrate that inhibition of axon regeneration is induced directly by engaging cell surface gangliosides in vivo and imply that circulating autoimmune antibodies can inhibit axon regeneration through neuronal gangliosides independent of endogenous regeneration inhibitors such as MAG.
    Journal of Neuroscience 02/2007; 27(1):27-34. · 6.91 Impact Factor
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    ABSTRACT: 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.
    Journal of Neuroscience Research 11/2006; 84(5):1085-90. · 2.97 Impact Factor
  • Gang Zhang, Pablo H H Lopez, Kazim A Sheikh
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    ABSTRACT: Intravenous immunoglobulin (IVIg) is used for the treatment of a number of autoimmune neurological disorders. Whether different brands of IVIg or different lots of the same brand are comparably efficacious for the treatment of neurological disorders is not clear. To examine this issue we compared the efficacy of different brands and/or lots of IVIg in a cell culture model of immune neuropathy. We report that products examined were equally effective and there was no lot-to-lot variability in our experimental model. These findings support the notion that efficacy of different IVIg products is comparable in a standardized model.
    Journal of Neuroimmunology 05/2006; 173(1-2):200-3. · 3.03 Impact Factor
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    ABSTRACT: High titers of anti-GA1 antibodies have been associated with neurological syndromes. In most cases, these antibodies cross-react with the structurally related glycolipids GM1 and GD1b, although specific anti-GA1 antibodies have also been reported. The role of specific anti-GA1 antibodies is uncertain since the presence of GA1 in the human nervous system has not been clarified. A rabbit was immunized with GD1a and its sera were screened for antibody reactivity by standard immunoassay methods (HPTLC-immunostaining and ELISA). Anti-GD1a antibodies were not detected but, unexpectedly, anti-GA1 IgG-antibodies were found. Antibody binding to GA1 was inhibited by soluble GA1 but also by GD1a. These results indicate that the rabbit produced antibodies that recognize epitopes present on the glycolipids, that are absent or not exposed on solid phase adsorbed GD1a. We investigated the presence of these unusual anti-ganglioside antibodies in normal and neurological patient sera. Approximately, 10% of normal human sera contained low titer of specific anti-GA1 IgG-antibodies but none of them recognized soluble GD1a. High titers of IgG-antibodies reacting only with GA1 were detected in 12 patient sera out of 325 analyzed. Of these, 6 sera showed binding that was inhibited by soluble GD1a and four of them also by GM1. This new type of anti-ganglioside antibodies should be considered important elements for understanding of the pathogenesis of these diseases as well as their diagnosis.
    Biochimica et Biophysica Acta 04/2006; 1762(3):357-61. · 4.66 Impact Factor
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    Pablo H H Lopez, Ronald L Schnaar
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    ABSTRACT: Glycolipids are found on all eukaryotic cells. Their expression varies among tissues, with the highest density found in the brain, where glycolipids are the most abundant of all glycoconjugate classes. In addition to playing roles in membrane structure, glycolipids also act as cell surface recognition molecules, mediating cell-cell interactions, as well as binding certain pathogens and toxins. Because of their amphipathic nature, underivatized glycolipids are amenable to immobilization on hydrophobic surfaces, where they can be probed with lectins, antibodies, pathogens, toxins, and intact cells to reveal their binding specificities and affinities. Three particularly useful methods to probe specific glycolipid-mediated recognition events are microwell adsorption (ELISA), thin layer chromatography overlay, and surface plasmon resonance (SPR) spectroscopy.
    Methods in Enzymology 02/2006; 417:205-20. · 2.00 Impact Factor
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    ABSTRACT: In sera from normal rats and from rats injected with whole myelin in complete Freund adjuvant to induce EAE we study the presence of antibodies capable to inhibit the reactivity of autoantibodies directed to myelin basic protein (MBP). Sera from rats that developed or not clinical signs of EAE were obtained previously to immunization, at acute stage of the disease and when the animals were completely recuperated, and chromatographied on a protein G-Sepharose column to obtain the retained (IgG) fractions. Then these fractions were depleted of anti-MBP reactivity by affinity chromatography and the ability of these depleted sera to block the reactivity of anti-MBP IgG antibodies was analyzed by an immunoblot technique. IgG fractions from preimmune sera inhibited the anti-MBP IgG reactivity associated to EAE. The analysis of sick EAE animals showed that the inhibitory activity faded away with the onset of the clinical signs but returned at its maximum value during the spontaneous remission. Animals that never developed clinical EAE did not show changes in the level of inhibitory activity that was similar to that observed in the preimmune sera. The presence of IgG antibodies blocking the anti-MBP IgG reactivity correlates with the development of the clinical signs of EAE.
    Journal of Neuroimmunology 08/2005; 164(1-2):31-6. · 3.03 Impact Factor
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    ABSTRACT: Antibodies against GD1a, GM1 and related gangliosides are frequently present in patients with the motor variant of Guillain-Barré syndrome (GBS), and their pathological role in this variant of GBS is now widely accepted. However, two basic issues related to anti-ganglioside antibody-mediated neural injury are not completely resolved: (i) some anti-ganglioside antibodies can cross-react with glycoproteins and therefore the nature of antigens targeted by these antibodies is not well established; and (ii) although pathological studies suggest that complement activation occurs in GBS, experimental data for the role of complement remain inconclusive. To address these issues, we developed and characterized a simple anti-ganglioside antibody-mediated cytotoxicity assay. Our results demonstrate first, that both GBS sera containing anti-ganglioside antibodies and monoclonal anti-ganglioside antibodies cause neuronal cell lysis by targeting specific cell surface gangliosides, and secondly, that this cell lysis is complement dependent. In this assay, the GD1a cell membrane pool appears to be more susceptible to anti-ganglioside antibody-mediated injury than the GM1 pool. Further, human intravenous immunoglobulin (i.v.Ig), now a standard treatment for GBS, significantly decreased cytotoxicity in this assay. Our data indicate that the mechanisms of i.v.Ig-mediated protection in this assay include anti-idiotypic antibodies and downregulation of complement activation. This simple cytotoxicity assay can potentially be used for screening of (i) pathogenic anti-ganglioside antibodies in patients with immune-mediated neuropathies; and (ii) new/experimental therapies to prevent anti-ganglioside antibody-mediated neural injury.
    Brain 06/2004; 127(Pt 5):1085-100. · 10.23 Impact Factor
  • P H H Lopez, A M Villa, R E P Sica, G A Nores
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    ABSTRACT: Elevated titers of serum anti-GM(1) antibodies of IgG isotype are found frequently in patients with Guillain-Barré syndrome. Much evidence indicates that these autoantibodies are involved in disease progression, but their exact function and the mechanism of their appearance are still unclear. In an attempt to reproduce "ganglioside syndrome", the experimental model of neuropathy developed by Nagai et al. (Neurosci. Lett. 2 (1976) 107), rabbits were intensively immunized with GM(1) in complete Freund adjuvant (CFA). High titers of anti-GM(1) antibodies were produced, with class switch and affinity maturation indicating an elaborate immune response. Unexpectedly, the rabbits did not show any clinical symptoms of neuropathy. Relatively affinities of both IgM and IgG antibodies were significantly lower than those of similar antibodies from neuropathy patients. These results suggest the existence of a threshold value above which affinity of anti-GM(1) antibodies becomes an important factor in disease induction. The absence of neuropathy symptoms in rabbits may be explained by absence of these high-affinity anti-GM(1) antibodies.
    Journal of Neuroimmunology 08/2002; 128(1-2):69-76. · 3.03 Impact Factor
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    ABSTRACT: Elevated titers of serum antibodies against GM1-ganglioside are associated with a variety of autoimmune neuropathies. The origin of these autoantibodies is still unknown, although there is evidence that they are produced by CD5+ B-lymphocytes and that antigen mimicry is involved. Anti-GM, IgM-antibodies in the normal human immunological repertoire are low affinity antibodies that cross-react with other glycoconjugates carrying Gal beta1-3GalNAc and probably do not have GM1-mediated biological activity. Other anti-GM1 IgM-antibodies with higher affinity and/or different fine specificity are present in patients with motor syndromes. Based on our studies of structural requirement for binding, we hypothesize that disease-associated anti-GM1 antibodies originate at random by mutations affecting the binding site of naturally-occurring ones. The hypothesis is conceptually similar to the established phenomenon of "genetic drift" in species evolutionary biology and is therefore termed "binding site drift".
    Neurochemical Research 08/2002; 27(7-8):687-95. · 2.13 Impact Factor
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    ABSTRACT: Aberrant O-glycosylation of cell surface mucin antigens is characteristic of epithelial cancer cells. For example, Thomsen-Friedenreich disaccharide (TFD) is a chemically well-defined carbohydrate antigen with a documented link to malignancy. There have been many attempts to improve immune response to carbohydrate antigens, for use in immunotherapy. As part of an alternative strategy to improve carbohydrate immunogenicity, we studied the influence of terminal benzyl (Bzl) or p-nitrophenyl (pNP) residue on immunogenicity of adjacent TFD. Mice immunized with keyhole limpets hemocyanin-TFD (KLH-TFD), KLH-TFD(alpha)Bzl, or KLH-TFD(alpha)pNP produced anti-KLH antibodies, which were analyzed by enzyme-linked immunosorbent assay (ELISA). KLH-TFD did not give significant anti-TFD antibody titer, confirming the poor immunogenicity of TFD. Immunization with KLH-TFD(alpha)Bzl and KLH-TFD(alpha)pNP raised antibody titers against TFD(alpha)Bzl and TFD(alpha)pNP, respectively. KLH-TFD(alpha)Bzl also gave higher anti-TFD antibody response, whereas KLH-TFD(alpha)pNP did not, indicating that terminal Bzl residue improves immune response to adjacent carbohydrate. Analysis of anti-TFD(alpha)Bzl or anti-TFD(alpha)pNP IgG antibodies by competitive ELISA, using carbohydrate-related antigens as inhibitors, demonstrated their high specificity to their respective antigens. Anti-TFD(alpha)pNP antibody was not inhibited by TFD, but was significantly inhibited by GalNAc(alpha)pNP. The fact that p-nitrophenol (pNPol) has more competitive ability that GalNAc indicates that terminal polar residue is the main target antigen. In contrast, anti-TFD(alpha)Bzl antibody was inhibited to a similar degree by GalNAc(alpha)Bzl and TFD, confirming the carbohydrate recognition by antibodies yielded by terminal non-polar modification of the immunogen.
    Molecular Immunology 04/2002; 38(11):825-31. · 2.65 Impact Factor
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    ABSTRACT: Recent studies have shown that antiganglioside antibodies, particularly those associated with the disialosyl group, may be involved in immune-mediated sensory peripheral neuropathies. We report the results of plasma screening for antiganglioside antibodies in two patients with chronic ataxic neuropathy. We found reactivity against gangliosides GD3, GD1b, and GT1b in one of them and against GD1a in the other, even though both had nearly identical clinical pictures. Results suggest that anti-GD1a antibodies, which are usually associated with motor polyneuropathy, may also be involved in the pathogenesis of clinically pure sensory polyneuropathy.
    Medicina 02/2002; 62(3):237-40. · 0.42 Impact Factor

Publication Stats

455 Citations
119.07 Total Impact Points

Institutions

  • 2006–2012
    • Johns Hopkins University
      • • Department of Pharmacology and Molecular Sciences
      • • Department of Neurology
      Baltimore, MD, United States
    • University of Maryland, Baltimore
      • Department of Neurology
      Baltimore, MD, United States
  • 2011
    • University of Texas Medical School
      • Department of Neurology
      Houston, Texas, United States
  • 2007–2009
    • Johns Hopkins Medicine
      • • Department of Pharmacology and Molecular Sciences
      • • Department of Neurology
      Baltimore, MD, United States
  • 1997–2006
    • National University of Cordoba, Argentina
      • • Faculty of Chemical Science
      • • Department of Biological Chemistry
      Córdoba, Córdoba, Argentina
  • 2001–2002
    • University of Cordoba (Spain)
      • Departamento de Bioquímica y Biología Molecular
      Córdoba, Andalusia, Spain
  • 2000–2001
    • Centro de Investigaciones en Química Biológica de Córdoba
      Córdoba, Córdoba, Argentina