Activation of terminal components of complement in patients with Guillain-Barré syndrome and other demyelinating neuropathies.
In the present study, the role of antiperipheral nerve myelin antibody (anti-PNM Ab) in demyelination by generating the terminal attack complex (C5b-9) of complement was explored in patients with Guillain-Barré syndrome (GBS) and other demyelinating neuropathies. The presence in serum of SC5b-9, an inactive C5b-9 containing S protein, was assessed quantitatively by enzyme-linked immunosorbent assay using an antibody (Ab) to neoantigens expressed on C9 when complexed with C5b-8 or after tubular polymerization. SC5b-9 was detected in all 19 GBS, four patients with paraprotein-associated neuropathy and five of six patients with chronic recurrent polyneuritis. No SC5b-9 was detected in 10 normal controls. Kinetic studies from six GBS patients showed the highest values of SC5b-9 on the 3rd to 5th d of admission; in contrast, the anti-PNM Ab were highest on the day of admission. Anti-PNM Ab fell rapidly to very low levels by the 15th to 20th d. SC5b-9 declined with similar kinetics to undetectable levels by the 30th d. Levels of Ab and SC5b-9 did not quantitatively correlate with soluble immune complexes in these patients' serum. Membrane-bound C5b-9 was also detected by immunohistochemistry in the peripheral nerves from a GBS patient. These results, which show a relationship between levels of complement-fixing anti-PNM Ab and the tissue-damaging C5b-9 complex, suggest that peripheral nerve myelin may serve as the target for Ab-mediated complement attack.
Koski
C L
CL
Department of Neurology, University of Maryland School of Medicine, Baltimore 21201.
Sanders
M E
ME
Swoveland
P T
PT
Lawley
T J
TJ
Shin
M L
ML
Frank
M M
MM
Joiner
K A
KA
D000936:Antigen-Antibody Complex / Q000032:analysis / Q000276:immunology; D001323:Autoantibodies / Q000032:analysis / Q000276:immunology*; D003167:Complement Activation; D015938:Complement Membrane Attack Complex; D003165:Complement System Proteins / Q000032:analysis / Q000276:immunology*; D003711:Demyelinating Diseases / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D006023:Glycoproteins / Q000032:analysis / Q000276:immunology*; D006801:Humans; D007700:Kinetics; D009186:Myelin Sheath / Q000276:immunology*; D010525:Peripheral Nerves / Q000276:immunology; D011129:Polyradiculoneuropathy / Q000276:immunology*
D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D015938:Complement Membrane Attack Complex; D006023:Glycoproteins; C047610:SC5b-9 protein complex; D003165:Complement System Proteins