IgG entry and deposition are components of the neuroimmune response in Batten disease

Ming J. Lim, Noreen Alexander, Jared W. Benedict, Subrata Chattopadhyay, Stephen J.A. Shemilt, Christopher J. Guérin, Jonathan D. Cooper, David A. Pearce

Research output: Contribution to journalArticlepeer-review

55 Scopus citations


Patients and a mouse model of Batten disease, the juvenile form of neuronal ceroid lipofuscinosis (JNCL), raise autoantibodies against GAD65 and other brain-directed antigens. Here we investigate the adaptive component of the neuroimmune response. Cln3-/- mice have autoantibodies to GAD65 in their cerebrospinal fluid and elevated levels of brain bound immunoglobulin G (IgG). IgG deposition was found within human JNCL autopsy material, a feature that became more evident with increased age in Cln3-/- mice. The lymphocyte infiltration present in human and murine JNCL occurred late in disease progression, and was not capable of central/intrathecal IgG production. In contrast, we found evidence for an early systemic immune dysregulation in Cln3-/- mice. In addition evidence for a size-selective breach in the blood-brain barrier integrity in these mice suggests that systemically produced autoantibodies can access the JNCL central nervous system and contribute to a progressive inflammatory response.

Original languageEnglish
Pages (from-to)239-251
Number of pages13
JournalNeurobiology of Disease
Issue number2
StatePublished - Feb 2007


  • Autoimmunity
  • Batten disease
  • Blood-brain barrier
  • Brain-directed autoantibody
  • GAD65 autoantibody
  • Neuroinflammation
  • Neuronal ceroid lipofuscinoses


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