Use of an anti-idiotypic monoclonal antibody in studying amyloidogenic light chains in cells, urine and fibrils: pathophysiology and clinical implications.
A monoclonal anti-idiotype antibody (IgG1k MoAb 3B11D4) raised against the amyloidogenic DEP lambda chain dimer binds a conformational idiotope also present on the monoclonal DEP IgA immunoglobulin. MoAb 3B11D4 does not recognize the reduced and alkylated lambda chain monomers, nor the 15-17-kDa fibrillar light chain fragments which have the same N-terminal sequence of the urinary light chains. The lack of about 70 amino acid residues of the C terminal of the protein prevents the formation of the self-limiting dimer and may facilitate the deposition of the fragments into amyloid fibrils. MoAb 3B11D4 recognizes the plasma cell clone in bone marrow and 9% of circulating B lymphocytes. Panning experiments demonstrate that this antibody has the capability to selectively eliminate the idiotype positive cells from peripheral blood. Antibodies with these characteristics could become a useful tool for better understanding the pathogenesis of the disease and for new therapeutic options.
Bellotti
V
V
Clinica Medica II, University Hospital Policlinico S. Matteo, Pavia, Italy.
Stoppini
M
M
Perfetti
V
V
Zorzoli
I
I
Marinone
G
G
Invernizzi
R
R
Zambelli
L M
LM
Arbustini
E
E
Grasso
M
M
Ferri
G
G
D000595:Amino Acid Sequence; D000686:Amyloidosis / Q000209:etiology* / Q000276:immunology / Q000628:therapy; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000627:therapeutic use; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000032:analysis*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D008969:Molecular Sequence Data
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D007147:Immunoglobulin Light Chains