Characterization of antibodies directed against the immunoglobulin light kappa chain variable chain region (VK) of hepatitis C virus-related type-II mixed cryoglobulinemia and B-cell proliferations.
Autoimmune type-II cryoglobulinemia (II-MC) is sustained by hepatitis C virus (HCV) infection and B-cell (oligo)clones. This is the reason why the disease may be considered an "indolent B-cell lymphoma (NHL)." B clones show a restricted use of immunoglobulin variable genes (BCR), in particular in the use of the variable kappa (VK)3-20/15 light chain, and show a homology between their BCR functional regions and those of autoimmune rheumatoid factors. We underlined the BCR unique repertoire with frequent rheumatoid factor activity also observed in other autoimmune disorders associated with NHL. The immunoglobulin idiotype is a clonal B-cell marker and an ideal target for immunotherapy. Five monoclonal antibodies were produced in our laboratory toward the VK3-20 of a subject with HCV infection and a II-MC-associated NHL. Epitope determination was performed using the epitope excision approach. Monoclonal antibody reactivity was tested in vitro in ELISA, Western blot, and cytofluorimetry. Data confirmed that a panel of antibodies, reactive against shared idiotypes, can be produced from patients with HCV-associated B-cell lymphoproliferative diseases, thus obviating the need to produce an anti-idiotype antibody for each patient.
de Re
Valli
V
Experimental and Clinical Pharmacology Unit, Dipartimento di Oncologia Molecolare e Ricerca Traslazionale, Centro di Riferimento Oncologico, IRCCS, National Cancer Institute, Franco Gallini, 2, 33081 Aviano (PN), Italy. vdere@cro.it
Simula
Maria Paola
MP
Pavan
Alessandro
A
Garziera
Marica
M
Marin
Dolores
D
Dolcetti
Riccardo
R
de Vita
Salvatore
S
Sansonno
Domenico
D
Geremia
Silvano
S
Toffoli
Giuseppe
G
D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology / Q000821:virology; D049109:Cell Proliferation; D003449:Cryoglobulinemia / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D005434:Flow Cytometry; D016174:Hepacivirus / Q000276:immunology; D006526:Hepatitis C / Q000276:immunology / Q000821:virology; D006801:Humans; D007114:Immunization; D015151:Immunoblotting; D007128:Immunoglobulin Fragments / Q000235:genetics; D007130:Immunoglobulin Idiotypes / Q000235:genetics / Q000276:immunology*; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007145:Immunoglobulin kappa-Chains / Q000235:genetics; D016393:Lymphoma, B-Cell / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C
D000911:Antibodies, Monoclonal; D000939:Epitopes; D007128:Immunoglobulin Fragments; D007130:Immunoglobulin Idiotypes; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains