BAFF, a new target for intravenous immunoglobulin in autoimmunity and cancer.
Intravenous immunoglobulin (IVIg) has been used to treat autoimmune diseases and lymphoid malignancies with some therapeutic effect. In both these pathological conditions, there is an overproduction of BAFF (for "B-cell-activating factor of the TNF family"), and APRIL (for "a proliferation-inducing ligand"). The presence of antibodies (Abs) with BAFF and APRIL specificities in IVIg preparations was investigated by enzyme-linked immunosorbent assay, and Western Blot analysis. Apoptosis was measured by the annexin-V binding method, and confirmed using the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling technique. Nonglycosylated recombinant BAFF, glycosylated affinity-purified BAFF, and recombinant APRIL (but not TNFalpha), were recognized by certain IgG in IVIg, and their F(ab')(2) fragments. Steric hindrance prevented the antiapoptotic effects of BAFF on B-lymphocytes. This work documents the presence of anti-BAFF and anti-APRIL Abs in IVIg. These can functionally neutralize the role of BAFF in B-cell survival. These anti-BAFF IgG might amend deleterious effects of BAFF in B-cell-mediated autoimmune diseases.
Le Pottier
Laëtitia
L
Department of Immunopathology, Brest University Medical School, Brest, France.
Bendaoud
Boutahar
B
Dueymes
Maryvonne
M
Daridon
Capucine
C
Youinou
Pierre
P
Shoenfeld
Yehuda
Y
Pers
Jacques-Olivier
JO
D000293:Adolescent; D000941:Antigens / Q000276:immunology; D017209:Apoptosis; D015551:Autoimmunity / Q000276:immunology*; D053264:B-Cell Activating Factor / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D002478:Cells, Cultured; D002648:Child; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000276:immunology* / Q000627:therapeutic use*; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology* / Q000628:therapy; D011485:Protein Binding
D000941:Antigens; D053264:B-Cell Activating Factor; D016756:Immunoglobulins, Intravenous; C505719:TNFSF13B protein, human