Immunoglobulin M deposition in cutaneous nerves of anti-myelin-associated glycoprotein polyneuropathy patients correlates with axonal degeneration.
Anti-myelin-associated glycoprotein (MAG) neuropathy is an antibody-mediated polyneuropathy. We correlated clinical features, immunoglobulin (Ig) M blood levels, IgM deposition and axonal degeneration in skin biopsies of anti-MAG neuropathy patients. By confocal microscopy, IgM deposits were found exclusively within perineurium-enclosed nerves; they were not found on single, non-perineurium-ensheathed myelinated axons. There was a linear correlation between IgM accumulation in nerve fascicles with IgM blood levels but not with anti-MAG antibody titer or disease duration. Axons with specific IgM deposits had signs of axonal damage, including neurofilament disintegration. Nodal structures were intact even at sites where the axons showed pathologic changes. Ultrastructural analysis revealed degeneration of myelinating Schwann cells. Taken together, these findings suggest that in anti-MAG neuropathy patients, IgM deposits are entrapped within cutaneous perineurium-ensheathed nerve bundles where they accumulate in the endoneurial space. High local IgM levels in the endoneurium may be required for IgM deposition on myelin and subsequent axonal injury and degeneration. This study underlines the importance of early, effective anti-B-cell treatments for preventing progression of this neuropathy.
Stalder
Anna K
AK
Neurobiology, Department of Biomedicine and Neurology, University Hospital Basel, Basel, Switzerland.
Erne
Beat
B
Reimann
Regina
R
Renaud
Susanne
S
Fuhr
Peter
P
Thomann
Sandra
S
Arnold
Andreas
A
Probst
Alphonse
A
Schaeren-Wiemers
Nicole
N
Steck
Andreas J
AJ
D000368:Aged; D001706:Biopsy; D005260:Female; D006801:Humans; D007075:Immunoglobulin M / Q000032:analysis / Q000097:blood*; D037102:Lectins; D008297:Male; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D008875:Middle Aged; D009186:Myelin Sheath / Q000276:immunology / Q000473:pathology*; D018992:Myelin-Associated Glycoprotein; D009363:Neoplasm Proteins / Q000276:immunology*; D009413:Nerve Fibers, Myelinated / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016900:Neurofilament Proteins / Q000378:metabolism; D010525:Peripheral Nerves / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D011115:Polyneuropathies / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology; D012583:Schwann Cells / Q000276:immunology / Q000473:pathology; D011984:Sensory Receptor Cells / Q000276:immunology / Q000473:pathology*; D012867:Skin / Q000294:innervation; D014855:Wallerian Degeneration / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology
D007075:Immunoglobulin M; D037102:Lectins; C115082:MAG protein, human; D018992:Myelin-Associated Glycoprotein; D009363:Neoplasm Proteins; D016900:Neurofilament Proteins