Pathogenesis of the neurotoxicity caused by anti-GD2 antibody therapy.
After treatment of melanomas with anti-GD2 monoclonal antibody (MAb) (14G2a), some patients develop sensorimotor demyelinating polyneuropathy with and without the syndrome of inappropriate antidiuretic hormone (SIADH). To clarify what causes the neurotoxicity of anti-GD2 MAb, we investigated the immunohistochemical localization of GD2 in the human nervous system. Anti-GD2 MAb (14G2a) reacted with the myelin sheaths in the peripheral nerves as well as with the pituicyte cytoplasm in the posterior lobe of the pituitary gland. We assume that the binding of anti-GD2 MAb to peripheral nerve myelin and the pituicytes in the posterior pituitary causes sensorimotor demyelinating neuropathy and SIADH.
Yuki
N
N
Department of Biochemistry, Faculty of Medicine, Tokyo Medical and Dental University, Japan. yuki@dokkyomed.ac.jp
Yamada
M
M
Tagawa
Y
Y
Takahashi
H
H
Handa
S
S
D000818:Animals; D000911:Antibodies, Monoclonal / Q000633:toxicity*; D001706:Biopsy; D002490:Central Nervous System / Q000737:chemistry / Q000473:pathology; D003711:Demyelinating Diseases / Q000139:chemically induced* / Q000209:etiology / Q000473:pathology; D005678:G(M2) Ganglioside / Q000032:analysis / Q000276:immunology*; D006801:Humans; D007177:Inappropriate ADH Syndrome / Q000139:chemically induced / Q000209:etiology / Q000473:pathology; D008545:Melanoma / Q000556:secondary / Q000628:therapy; D051379:Mice; D009186:Myelin Sheath / Q000737:chemistry / Q000473:pathology; D009498:Neurotoxins / Q000494:pharmacology; D009802:Oculomotor Nerve / Q000737:chemistry / Q000473:pathology; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000209:etiology / Q000473:pathology; D010902:Pituitary Gland / Q000737:chemistry / Q000473:pathology; D013497:Sural Nerve / Q000737:chemistry / Q000473:pathology; D013979:Tibial Nerve / Q000737:chemistry / Q000473:pathology; D014321:Trochlear Nerve / Q000737:chemistry / Q000473:pathology
D000911:Antibodies, Monoclonal; D009498:Neurotoxins; D005678:G(M2) Ganglioside