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. CONCLUSION: 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.
RCT Entities:
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 humanlupus nephritis. We investigated whether nucleosomes are present in the basement membrane of nonlesional skin of lupuspatients. 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 nephritispatients, but in none of the other SLEpatients 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 nephritispatients. 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. CONCLUSION: 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.
Authors: J F Carvalho; V S T Viana; E F Borba; A P do Nascimento; E P Leon; L A Testagrossa; R T Barros; E Bonfá Journal: Clin Rheumatol Date: 2008-06-04 Impact factor: 2.980