Inositol 1,4,5-trisphosphate receptor type 1 autoantibodies in paraneoplastic and non-paraneoplastic peripheral neuropathy.

摘要: Recently, we described a novel autoantibody, anti-Sj/ITPR1-IgG, that targets the inositol 1,4,5-trisphosphate receptor type 1 (ITPR1) in patients with cerebellar ataxia. However, ITPR1 is expressed not only by Purkinje cells but also anterior horn of spinal cord, substantia gelatinosa and motor, sensory (including dorsal root ganglia) autonomic peripheral nervous system, suggesting clinical spectrum associated autoimmunity to may be broader than initially thought. Here report on serum autoantibodies (up 1:15,000) three (radiculo)polyneuropathy, which two cases was cancer (ITPR1-expressing adenocarcinoma lung, multiple myeloma), paraneoplastic aetiology. Serological other immunological studies, retrospective analysis patient records. The findings comprised severe pain) symptoms. While one presented subacute symptoms mimicking Guillain-Barre syndrome (GBS), progressed slowly patients. Electrophysiology revealed delayed F waves; decrease motor action potentials conduction velocities; latencies; signs denervation, indicating sensorimotor radiculopolyneuropathy mixed type; no blocks. ITPR1-IgG belonged complement-activating IgG1 subclass severely affected exclusively IgG2 more mildly Cerebrospinal fluid found predominantly extrathecal origin. A 3H-thymidine-based proliferation assay confirmed presence ITPR1-reactive lymphocytes among blood mononuclear (PBMCs). Immunophenotypic profiling PBMCs protein demonstrated predominant B cells, CD4 T CD8 memory following stimulation purified protein. Patient bound both tissue lung tumour tissue. nerve biopsy showed lymphocyte infiltration cytotoxic cells), oedema, marked axonal loss myelin-positive macrophages, florid inflammation. titres declined removal, paralleled stabilization. Our expand syndromes suggest underlie system diseases GBS) some origin subset cases.