Pathogenesis of Neuropsychiatric Systemic Lupus Erythematosus – Prof Graham Hughes

Posted on December 15, 2016

Graham Hughes trained at The London Hospital. In 1969-70, he spent two years with Professor Charles Christian in New York working on the introduction of anti-DNA assays in lupus. He set up Europe’s first dedicated lupus clinic in 1971 and described the antiphospholipid syndrome (Hughes Syndrome) in 1983. Professor Hughes has published widely on lupus and connective tissue diseases and has published twelve books.

I personally believe that Lupus is a primary neurologic disease in which other organs may be involved.

What are the mechanisms of CNS Lupus?

  • Antibody-mediated
  • Blood-brain barrier breakdown
  • Blood flow abnormalities

In the murine neuropsychiatric lupus the blood-brain barrier is abnormal.

It is suggested that transient disturbances of cerebral vascular function in SLE might allow brain-reactive antibodies from the circulation access to cerebral tissue.  The neuropsychiatric lupus brain had abnormal levels of oxygen uptake in various parts of the brain; “this was a precursor to the SPECT studies”

 We found that there was an association of lymophocytotoxic antibodies with cerebral involvement in SLE… What was very interesting was when you looked at absorption with brain homogenates it was those with neuropsychiatric disease that absorbed out these antibodies, suggesting a cross-reactivity with antibodies.

Risk Factors for CNS Lupus (Italian study findings of approx 1000 patients):

There were three things that were highly associated with CNS Lupus.

  • Antiphospholipid antibodies
  • Lupus anticoagulant
  • Low platelets
  • “Your classic things like Malar rash were not associated ; this may be a subset of Lupus.”

Epilepsy and Antiphospholipid Syndrome:

  • Epilepsy in SLE is associated with APS (Mackworth-Young & Hughes 1984)
  • ‘Idiopathic’ childhood epilepsy 28% antiphospholipid positive (Cimaz et al 2002)


  1. Bresnihan, B., et al. “The neuropsychiatric disorder in systemic lupus erythematosus: evidence for both vascular and immune mechanisms.” Annals of the rheumatic diseases 38.4 (1979): 301-306.
  2. Bresnihan, B., Oliver, M., Grigor, R., & Hughes, G. R. (1977). Brain reactivity of lymphocytotoxic antibodies in systemic lupus erythematosus with and without cerebral involvement. Clinical and experimental immunology, 30(3), 333.
  3. Padovan, M., Castellino, G., Bortoluzzi, A., Caniatti, L., Trotta, F., & Govoni, M. (2012). Factors and comorbidities associated with central nervous system involvement in systemic lupus erythematosus: a retrospective cross-sectional case–control study from a single center. Rheumatology international, 32(1), 129-135.
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