• Yu, Robert K (PI)
  • YU, ROBERT K. (PI)
  • YU, ROBERT K. (PI)
  • YU, ROBERT K. (PI)
  • [No Value], Robert K. (PI)

Project: Research project

Project Details


In some patients with polyneuropathy there are IgM monoclonal
antibodies (m-proteins) that bind to peripheral nerve myelin and
that may cause the neuropathy. These M-proteins bind to
carbohydrate determinants that are shared by a number of peripheral
nerve glycoproteins, including the myelin-associated glycoprotein
(MAG), and two glycolipids in peripheral nerve. We have
characterized these two glycolipids from human cauda equina and
found that they belong to a new class of glycolipids termed
sulfated glucuronyl-glycolipids (SGGLs). Subcellular localization
studies of bovine peripheral nerve have demonstrated that they are
enriched in the axolemma-enriched fraction, while present in myelin
and other glial-related membranes in lower concentrations. In
addition, these glycolipids are present in bovine dura master and
transformed rat Schwann cells. In this project, we plan to further
characterize the antigenic determinant(s) that bind to M-proteins
in patients with neuropathy and to develop synthetic analogues of
the antigenic epitopes. These analogues could then be used
therapeutically to block or remove circulating M-proteins in
patients and improve the neuropathy. To better understand the role
of these glycolipids in the pathogenesis of this disorder, we plan
to immunize animals with SGGLs to induce experimental allergic
neuritis (EAN) and to obtain polyclonal antibodies against these
peripheral nerve glycolipids. Establishing the EAN model with
structurally well-defined glycolipid antigens should be extremely
important in affording a direct proof that these antigens can
actually cause the neuropathy. The polyclonal antisera will be
useful in studying their demyelinating and myelination-inhibiting
activities in vitro and in vivo, in developing sensitive assays for
quantitating these antigens, and for the immunocytochemical
localization of these antigens in the nerve. Once this animal
model is established, the pathogenetic mechanisms underlying this
disorder can be studied in terms of humoral and cellular immune
mechanisms, and T- and B-cell interactions regulating the secretion
of M-proteins. The results of this project would therefore be
important not only for understanding the pathogenesis and
pathophysiology of the demyelinating neuropathy associated with
IgM M-proteins and plasma cell dyscrasia, but also for providing
vital information on the mechanisms of other autoimmune diseases
such as multiple sclerosis, Guillain-Barre syndrome, etc.
Effective start/end date6/1/881/31/15


  • National Institutes of Health
  • National Institutes of Health


  • Medicine(all)
  • Neuroscience(all)


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