Accumulation of immunoglobulin across the 'blood-nerve barrier' in spinal roots in adoptive transfer experimental autoimmune neuritis.
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 micro Ci 125I-labelled immunoglobulin. Immunoglobulin accumulation in the roots of normal rats was 3 +/- 1% (mean +/- SE), but this first increased 3(1/2) days after cell injection, peaked at 22 +/- 2% on day 4(1/2), and declined to normal by day 8. T lymphocytes and polymorphonuclear leucocytes first appeared within the endoneurium at day 3(1/2), 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.
Hadden
R D M
RD
Department of Neuroimmunology, Guy's, King's and St Thomas' School of Medicine, Guy's Hospital, London, UK. rob.hadden@doctors.org.uk
Gregson
N A
NA
Gold
R
R
Smith
K J
KJ
Hughes
R A C
RA
D019264:Adoptive Transfer; D000818:Animals; D001812:Blood-Brain Barrier / Q000276:immunology*; D003711:Demyelinating Diseases / Q000473:pathology; D004912:Erythrocytes / Q000276:immunology / Q000648:ultrastructure; D005260:Female; D007136:Immunoglobulins / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology / Q000648:ultrastructure; D009410:Nerve Degeneration / Q000473:pathology; D009444:Neuritis, Autoimmune, Experimental / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology; D009504:Neutrophils / Q000276:immunology / Q000648:ultrastructure; D051381:Rats; D011917:Rats, Inbred Lew; D012584:Sciatic Nerve / Q000276:immunology / Q000473:pathology; D013126:Spinal Nerve Roots / Q000098:blood supply / Q000276:immunology* / Q000473:pathology* / Q000648:ultrastructure; D013601:T-Lymphocytes / Q000276:immunology / Q000648:ultrastructure
D007136:Immunoglobulins