Decreased staining of heparan sulfate in non-lesional skin of a subgroup of patients with systemic lupus erythematosus.
Heparan sulfate proteoglycans (HSPGs) are components of the basement membrane of various tissues. They are composed of a core protein and of the negatively charged glycosaminoglycan side chain heparan sulfate, which is covalently bound to the core protein. We previously found that in both human and murine lupus nephritis, heparan sulfate staining in the basement membrane of the glomerulus is almost completely absent, and that there was an inverse correlation between heparan sulfate staining and glomerular immunoglobulin deposits. As immunoglobulin deposits are also present in the skin of systemic lupus erythematosus patients, we investigated the heparan sulfate staining pattern in the basement membrane of the dermal-epidermal junction. furthermore, we studied whether there was a correlation between heparan sulfate staining and deposition of immunoglobulin in the basement membrane of this junction, and between heparan sulfate staining and the presence of anti-DNA antibodies in the serum. Biopsies of non-lesional skin of 21 systemic lupus erythematosus patients (15 anti-DNA positive and 6 anti-DNA negative patients at the time of biopsy) were stained for the HSPG-core protein (mAb JM-72), highly sulfated stretches within heparan sulfate (JM-13), the low sulfated regions of heparan sulfate (mAb JM-403) and for immunoglobulin depositions. Abnormal and discontinuous staining of the low sulfated parts of heparan sulfate using mAb JM-403 in the basement membrane was found in skin biopsies of 4 out of 15 systemic lupus erythematosus patients with anti-DNA antibodies. In contrast, all specimens of anti-DNA negative patients showed normal continuous staining. Staining with JM-13 and JM-72 showed normal linear staining in both groups. The decreased heparan sulfate staining was correlated significantly with the presence of immunoglobulin deposits in the basement membrane. The subgroup could not be identified by its clinical picture. Our results suggest similar but not identical pathways in systemic lupus erythematosus nephritis and skin of systemic lupus erythematosus patients.
Department of Dermatology, University Hospital Nijmegen, The Netherlands.
M M
MM
Seyger
M C
MC
van Bruggen
H K
HK
Hardeman
F H
FH
van den Hoogen
J H
JH
Berden
J
J
van den Born
E M
EM
De Jong
D000293:Adolescent; D000328:Adult; D000368:Aged; D000974:Antibodies, Antinuclear / Q000097:blood / Q000276:immunology; D001485:Basement Membrane / Q000737:chemistry / Q000276:immunology; D005260:Female; D019812:Heparan Sulfate Proteoglycans / Q000032:analysis; D006497:Heparan Sulfate / Q000032:analysis*; D006801:Humans; D007136:Immunoglobulins / Q000032:analysis; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012867:Skin / Q000737:chemistry* / Q000276:immunology; D013223:Statistics as Topic; D019063:Tenascin / Q000032:analysis
D000974:Antibodies, Antinuclear; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate; D007136:Immunoglobulins; D019394:Ki-67 Antigen; D019063:Tenascin