13-cis retinoic acid enhances in vivo B-lymphocyte differentiation in patients with common variable immunodeficiency.
Retinoic acid (RA) has been demonstrated to drive both phenotypic and functional in vitro differentiation of B cell hybridomas from patients with common variable immunodeficiency (CVI) who manifest an "intrinsic" defect in terminal B cell differentiation (J Exp Med 1988;168: 55-71). Therefore, we conducted an open trial to determine the effects of oral 13-cis RA (0.5 mg/kg/day; 12 weeks receiving and 12 weeks without drug) on in vivo B cell differentiation in subjects with CVI. At various times before, during, and after drug administration, patients' B cells were tested for changes in cell-surface phenotype and in vitro immunoglobulin production in response to recombinant cytokines. Before 13-cis RA, all patients had decreased Leu-8 coexpression on CD20+ cells. Seven of eight subjects demonstrated "normalization" of this phenotype after 8 to 16 weeks of 13-cis RA administration. Patients whose B cells demonstrated more than normal CD20 display also had a fall toward normal in this parameter. These effects persisted for 6 to 12 weeks after drug was stopped. It appears that 13-cis RA drives B cells of patients with CVI to express a more differentiated cell-surface phenotype and may promote functional differentiation in some patients.
Adelman
D C
DC
Department of Medicine, University of California, San Francisco School of Medicine 94143-0724.
Yen
T Y
TY
Cumberland
W G
WG
Sidell
N
N
Saxon
A
A
D000284:Administration, Oral; D000328:Adult; D000361:Agammaglobulinemia / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D000921:Antibody-Producing Cells / Q000187:drug effects; D000954:Antigens, Surface / Q000032:analysis; D001402:B-Lymphocytes / Q000276:immunology; D015815:Cell Adhesion Molecules; D002454:Cell Differentiation; D016207:Cytokines / Q000494:pharmacology; D005260:Female; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis; D016130:Immunophenotyping; D015474:Isotretinoin / Q000276:immunology / Q000627:therapeutic use*; D019041:L-Selectin; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000494:pharmacology
D000954:Antigens, Surface; D015815:Cell Adhesion Molecules; D016207:Cytokines; D007136:Immunoglobulins; D011994:Recombinant Proteins; D019041:L-Selectin; D015474:Isotretinoin