Chondroitin 6-sulfate proteoglycan but not heparan sulfate proteoglycan is abnormally expressed in skin basement membrane from patients with dominant and recessive dystrophic epidermolysis bullosa.

Two distinct groups of proteoglycans, chondroitin 6-sulfate (C6-S) proteoglycan and heparan sulfate proteoglycan (HSPG), have been recently shown to reside within the lamina densa of normal human skin basement membrane (BM). To determine whether either or both antigens are normally expressed in one or more forms of epidermolysis bullosa (EB), a disease known to have specific alterations in skin BM, we have examined by indirect immunofluorescence 31 specimens of clinically normal skin from 28 EB patients (simplex, 5; junctional, 8; dominant dystrophic [DDEB], 9; recessive dystrophic [RDEB], 9) with monoclonal antibodies to C6-S and HSPG. HSPG was normally expressed in all EB and control skin specimens, whereas C6-S was absent along the dermoepidermal junction of 9 of 9 RDEB and 7 of 9 DDEB, and reduced in 2 of 9 DDEB cases. In contrast, C6-S was normally expressed in 5 of 5 EB simplex, 5 of 6 junctional EB, and all control skin specimens. We have subsequently extracted a greater than 400 kD C6-S proteoglycan from normal skin BM and have found that the core protein may also contain heparan sulfate side chains. Our findings suggest that 3B3 monoclonal antibody recognizes a hybrid proteoglycan in human skin, and that its absent or reduced binding in dystrophic EB skin BM may reflect either absence of associated core protein or posttranslational alterations in the proteoglycan side chains.