Analysis of anti-GM1 ganglioside IgM antibodies cloned from motor neuropathy patients demonstrates diverse V region gene usage with extensive somatic mutation.

摘要: Serum anti-GM1 ganglioside Abs are abnormally elevated in patients with chronic motor neuropathies and Guillain-Barre syndrome. We have cloned six IgM from PBMCs of five affected patients. VH VL gene analysis demonstrated substantial somatic mutation, predominantly clustered around CDR2 FR3 all Abs. The SM1, DO1, WO1, isolated three different patients, encoded by closely related segments restricted canonical structures. corresponding L chains V lambda II VIII genes also share the same structures, containing nucleotide deletions at VL/JL boundary to form a VLCDR3 10 amino acids. DO1 WO1 show identities 95.6% 88.8%, respectively, VH3 member 1.9III, SM1 shows 87.8% identity member, Hv3005. BO1 BO3, derived single patient VH-D-JH VL-JL rearrangements, gene, HHg19, 92.2 91.2%, both common unique mutations. sequence BR1 has 91.3% VH4 V71-2. These data indicate that neuropathy-associated can be diverse association their somatically mutated, consistent an origin through Ag-driven immune response.