Cutaneous IgA deposits in bullous diseases function as ligands to mediate adherence of activated neutrophils.
Linear IgA bullous dermatosis and dermatitis herpetiformis are inflammatory subepidermal blistering diseases characterized by IgA deposits at the cutaneous epithelial basement membrane and in dermal papillae, respectively. Inflammation in both disorders localizes to sites of IgA deposition and is characterized by a predominance of neutrophils. From these observations we postulate that IgA deposits in both diseases may contribute to the recruitment and/or localization of neutrophils. In this study we examined the ability of in vitro and in vivo bound IgA anti-basement membrane autoantibodies from patients with linear IgA bullous dermatosis and in vivo bound IgA deposits in dermal papillae from patients with dermatitis herpetiformis to mediate adherence of neutrophils stimulated by granulocyte macrophage colony-stimulating factor. The study showed that stimulated neutrophils adhered to basement membranes and dermal papillae containing IgA deposits. Adherence was IgA anti-basement membrane antibody concentration dependent and correlated with the immunofluorescence staining intensity of IgA deposits in dermal papillae. Adherence to IgA deposits but not IgG deposits could be inhibited by purified exogenous secretory IgA but not IgG and adherence to IgG deposits could be inhibited by purified exogenous IgG but not secretory IgA. These results provide direct experimental evidence that cutaneous IgA deposits in linear IgA bullous dermatosis and dermatitis herpetiformis can function as ligands for neutrophil adherence and have a role in the localization of inflammation in these disorders.
Hendrix
J D
JD
Department of Dermatology, University of North Carolina School of Medicine, Chapel Hill 27514.
Mangum
K L
KL
Zone
J J
JJ
Gammon
W R
WR
D002448:Cell Adhesion; D003115:Colony-Stimulating Factors / Q000494:pharmacology; D003874:Dermatitis Herpetiformis / Q000473:pathology / Q000503:physiopathology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology / Q000378:metabolism*; D008024:Ligands; D008297:Male; D009504:Neutrophils / Q000166:cytology*; D011994:Recombinant Proteins / Q000494:pharmacology; D012867:Skin / Q000276:immunology*; D012872:Skin Diseases, Vesiculobullous / Q000473:pathology / Q000503:physiopathology*
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D007070:Immunoglobulin A; D008024:Ligands; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor