CSF IgG heavy-chain bias in patients at the time of a clinically isolated syndrome.
Using FACS and single cell reverse transcriptase polymerase chain reaction, we examined the cerebrospinal fluid (CSF) IgG VH repertoires from 10 subjects with a clinically isolated demyelinating syndrome (CIS). B and plasma cell repertoires from individual subjects showed similar VH family germline usage, nearly identical levels of post-germinal center somatic hypermutation, and significant overlap in their clonal populations. Repertoires from 7 of 10 CIS subjects demonstrated a biased usage of VH4 and/or VH2 family gene segments in their plasma or B cell repertoires. V-regionbias, however, was not observed in the corresponding peripheral blood CD19+ B cell repertoires from 2 CIS subjects or in normal healthy adults. Clinically, subjects with VH4 or VH2 CSF IgG repertoire bias rapidly progressed to definite MS, whereas individuals without repertoire bias did not develop MS after a minimum of 2 years of follow-up (p=0.01).
Department of Neurology, University of Colorado Health Sciences Center, Denver, CO, United States. jeffrey.bennett@uchsc.edu
Jeffrey L
JL
Bennett
Kurt
K
Haubold
Alanna M
AM
Ritchie
Sydni J
SJ
Edwards
Mark
M
Burgoon
Andrew J
AJ
Shearer
Donald H
DH
Gilden
Gregory P
GP
Owens
D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology; D003711:Demyelinating Diseases / Q000134:cerebrospinal fluid* / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007074:Immunoglobulin G / Q000134:cerebrospinal fluid*; D007143:Immunoglobulin Heavy Chains / Q000134:cerebrospinal fluid*; D007135:Immunoglobulin Variable Region / Q000134:cerebrospinal fluid; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000276:immunology; D010950:Plasma Cells / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region