Inhibition of neutrophil adherence to antibody by dapsone: a possible therapeutic mechanism of dapsone in the treatment of IgA dermatoses.
Dapsone is frequently effective in cutaneous diseases characterized by antibody deposition and accumulation of neutrophils. We hypothesized that this mechanism of action of dapsone may involve the inhibition of neutrophil adherence to antibody. The neutrophil adherence assay, which measures the binding of neutrophils to basement membrane zone-bound antibody on skin sections, was used to evaluate the effect of dapsone on neutrophil adherence to immunoglobulin A and immunoglobulin G. We evaluated the effect of dapsone on adherence of normal neutrophils to immunoglobulin A and immunoglobulin G from sera of linear immunoglobulin A bullous dermatosis and bullous pemphigoid patients, respectively. Linear immunoglobulin A bullous dermatosis or bullous pemphigoid antibody were bound to the basement membrane zone of normal skin sections as a substrate for the neutrophil adherence assay. Dapsone was added directly to the neutrophils or to the antibody source in concentrations of 0-50 micrograms/ml (pharmacologic range). Addition of dapsone to neutrophils produced an incremental inhibition of neutrophil adherence up to 75% at 50 micrograms/ml. Dapsone produced similar inhibition when added directly to the antibody itself, despite washing prior to usage in the neutrophil-adherence assay. Control specimens including irrelevant fractions of patient sera failed to demonstrate binding. Serum from a patient on dapsone therapy also showed inhibition of neutrophil adherence compared to the same patient on no therapy. We conclude that dapsone inhibits the adherence of neutrophils to basement membrane zone antibody in a dose-dependent manner. This may be related to an effect directly on antibody. This inhibition may contribute to the clinical efficacy of dapsone in antibody-mediated diseases.
Thuong-Nguyen
V
V
Dermatology Section, Veterans Affair Medical Center, Salt Lake City, Utah.
Kadunce
D P
DP
Hendrix
J D
JD
Gammon
W R
WR
Zone
J J
JJ
D000328:Adult; D001485:Basement Membrane / Q000276:immunology / Q000378:metabolism; D001666:Binding Sites, Antibody / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003622:Dapsone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007070:Immunoglobulin A / Q000032:analysis* / Q000187:drug effects / Q000378:metabolism; D007074:Immunoglobulin G / Q000378:metabolism; D009504:Neutrophils / Q000166:cytology*; D010391:Pemphigoid, Bullous / Q000276:immunology; D012872:Skin Diseases, Vesiculobullous / Q000188:drug therapy / Q000276:immunology*
D007070:Immunoglobulin A; D007074:Immunoglobulin G; D003622:Dapsone