Accumulation of immunoglobulin across the 'blood-nerve barrier' in spinal roots in adoptive transfer experimental autoimmune neuritis

• Published in: Neuropathology and applied neurobiology 2002-12, Vol.28 (6), p.489-497
• Main Authors: Hadden, R. D. M., Gregson, N. A., Gold, R., Smith, K. J., Hughes, R. A. C.
• Format: Article
• Language: English
• Subjects: Adoptive Transfer; Animals; Blood-Brain Barrier - immunology; blood-nerve barrier; Demyelinating Diseases - pathology; Erythrocytes - immunology; Erythrocytes - ultrastructure; experimental autoimmune neuritis; Female; Guillain-Barré syndrome; Immunoglobulin; Immunoglobulins - metabolism; Macrophages - immunology; Macrophages - ultrastructure; Nerve Degeneration - pathology; Neuritis, Autoimmune, Experimental - immunology; Neuritis, Autoimmune, Experimental - pathology; Neuritis, Autoimmune, Experimental - physiopathology; Neutrophils - immunology; Neutrophils - ultrastructure; polyradiculoneuritis; Rats; Rats, Inbred Lew; Sciatic Nerve - immunology; Sciatic Nerve - pathology; Spinal Nerve Roots - blood supply; Spinal Nerve Roots - immunology; Spinal Nerve Roots - pathology; Spinal Nerve Roots - ultrastructure; T-Lymphocytes - immunology; T-Lymphocytes - ultrastructure
• ISSN: 0305-1846; 1365-2990
• DOI: 10.1046/j.1365-2990.2002.00421.x

At the onset of Guillain–Barré syndrome, disruption of diffusion barriers, such as the blood–nerve barrier, probably increases the exposure of spinal roots and peripheral nerves to macromolecules, some of which might be pathogenic. As a measure of such disruption, we measured the accumulation in the endoneurium of spinal roots and sciatic nerve of systemically administered 125I‐labelled immunoglobulin in adoptive transfer experimental autoimmune neuritis (AT‐EAN) in the rat. AT‐EAN is a model of Guillain–Barré syndrome, induced by injection of activated T lymphocytes sensitized to myelin P2 protein. Immunoglobulin accumulation was expressed as counts/min/mg in fixative‐perfused roots as a percentage of that in serum, measured 24 h after intraperitoneal injection of 0.1 µCi 125I‐labelled immunoglobulin. Immunoglobulin accumulation in the roots of normal rats was 3 ± 1% (mean ± SE), but this first increased 3½ days after cell injection, peaked at 22 ± 2% on day 4½, and declined to normal by day 8. T lymphocytes and polymorphonuclear leucocytes first appeared within the endoneurium at day 3½, and macrophages and a few erythrocytes at day 4. Neurological deficit appeared on day 4 and was maximal on day 6. Demyelination and axonal degeneration began at day 5. The first abnormality detected in AT‐EAN was a rapid increase in the passage of immunoglobulin into spinal roots, together with endoneurial infiltration of T lymphocytes and polymorphonuclear leucocytes. Accumulation of immunoglobulin was maximal during the worsening of neurological deficit, and declined rapidly before the onset of neurological recovery.