Immunoglobulin gene analysis in polyneuropathy associated with IgM monoclonal gammopathy.
Antineural antibody activity is the implicated pathogenic mechanism in polyneuropathy associated with monoclonal gammopathy. Recognition of antigen depends on immunoglobulin variable regions, encoded by V genes. We studied V(H)DJ(H) and V(L)J(L) gene use in monoclonal B cells by clonal analysis in 20 patients with polyneuropathy and IgM monoclonal gammopathy. V genes associated with bacterial responses appear over-represented and V(H)3-23 was preferentially used, without association with specific D, J(H) or V(L)J(L). V genes revealed somatic mutation and intraclonal variation was found in 9 of 20 patients. Polyneuropathy associated with monoclonal gammopathy may be caused by an immune response to bacterial antigens, which recruit somatically mutated autoreactive B cells.
Eurelings
Marijke
M
Department of Neurology, the Rudolf Magnus Institute of Neuroscience, University Medical Centre Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. m.eurelings@neuro.azu.nl
Notermans
Nicolette C
NC
Lokhorst
Henk M
HM
van Kessel
Berris
B
Jacobs
Bart C
BC
Wokke
John H J
JH
Sahota
Surinder S
SS
Bloem
Andries C
AC
D000368:Aged; D016175:B-Lymphocyte Subsets / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D002999:Clone Cells; D005260:Female; D005803:Genes, Immunoglobulin; D006801:Humans; D007075:Immunoglobulin M / Q000737:chemistry / Q000235:genetics*; D007145:Immunoglobulin kappa-Chains / Q000235:genetics; D007146:Immunoglobulin lambda-Chains / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010265:Paraproteinemias / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D011115:Polyneuropathies / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D017422:Sequence Analysis, DNA
D007075:Immunoglobulin M; D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains