Deposition of nucleosomal antigens (histones and DNA) in the epidermal basement membrane in human lupus nephritis.
OBJECTIVE
Antinuclear autoantibodies complexed to nucleosomes can bind to heparan sulfate (HS) in the glomerular basement membrane. This binding is due to the binding of the positively charged histones to the strongly anionic HS. Nucleosomes and histones have been identified in glomerular deposits in human lupus nephritis. We investigated whether nucleosomes are present in the basement membrane of nonlesional skin of lupus patients.


METHODS
Skin biopsy samples from patients with systemic lupus erythematosus (SLE) (30 with active lupus nephritis and 15 with inactive disease) and controls (with parapemphigus or diabetes) were stained for IgG, histones, DNA, and nucleosomes.


RESULTS
IgG deposits were found in 87% of the patients with lupus nephritis, in 33% of the patients with inactive disease, and in 71% of the parapemphigus patients. Using polyclonal antihistone antibodies, histones were detected in 87% of lupus nephritis patients, but in none of the other SLE patients or the diabetes controls (P < 0.0001). Among the parapemphigus controls, 14% of samples stained positive in one of the polyclonal antihistone stainings (P < 0.0001). Using monoclonal antibodies, histones and DNA were identified in 21% of the lupus nephritis patients. Although none of the other groups showed positive staining for nucleosomes, 7% of the lupus nephritis biopsy samples were positive using antinucleosome monoclonal antibodies. Colocalization of nucleosomal antigens and IgG was confirmed using confocal laser microscopy.


CONCLUSIONS
These findings suggest that nucleosome-mediated binding of autoantibodies to basement membranes may also occur at sites in the body other than in the glomerulus.
University Medical Center, Nijmegen, The Netherlands. m.grootscholten@nier.umcn.nl
Cecile
C
Grootscholten
Mieke C J
MC
van Bruggen
Johan W
JW
van der Pijl
Elke M G J
EM
de Jong
Gerry
G
Ligtenberg
Ronald H W M
RH
Derksen
Jo H M
JH
Berden
D000328:Adult; D000936:Antigen-Antibody Complex / Q000378:metabolism; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001485:Basement Membrane / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D004247:DNA / Q000276:immunology / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D004359:Drug Therapy, Combination; D004817:Epidermis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D019085:Fluorescent Antibody Technique, Direct; D019084:Fluorescent Antibody Technique, Indirect; D006657:Histones / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D008181:Lupus Nephritis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D018613:Microscopy, Confocal; D009707:Nucleosomes / Q000276:immunology / Q000378:metabolism*; D010392:Pemphigus / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D011446:Prospective Studies; D012720:Severity of Illness Index
D000936:Antigen-Antibody Complex; D018501:Antirheumatic Agents; D006657:Histones; D007074:Immunoglobulin G; D009707:Nucleosomes; D004247:DNA