chondroitin and 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.

Topics: Basement Membrane; Chondroitin; Chondroitin Sulfates; Epidermolysis Bullosa; Fluorescent Antibody Technique; Genes, Dominant; Genes, Recessive; Glycosaminoglycans; Heparitin Sulfate; Humans; Proteoglycans; Skin

We studied two patients with an axonal type of polyneuropathy, epidermolysis, and IgM kappa plasma cell dyscrasia. The IgM kappa was deposited in the dermis, was absorbed from the serum by axonal micelle preparations, and was precipitated with chondroitin sulfate in highly purified agarose in 0.15 M NaCl with 0.01 M phosphate buffer, pH 7.8. In contrast, we found none of these abnormalities in three patients with IgM plasma cell dyscrasia and demyelinating neuropathy. Of 78 other macroglobulinemic serum samples from patients without neuropathy, 7 precipitated with a sulfated polysaccharide. This reaction occurred at low ionic strength, 0.05 M barbital buffer, pH 8.1, but did not occur in the higher ionic strength of 0.01 M phosphate with 0.15 M NaCl (PBS). The interaction of the IgM with chondroitin sulfate at relatively high ionic strength could cause both the axonal polyneuropathy and the epidermolysis.

Topics: Absorption; Antibodies, Monoclonal; Axons; Chondroitin; Chondroitin Sulfates; Epidermolysis Bullosa; Female; Humans; Immunoglobulin kappa-Chains; Immunoglobulin M; Male; Middle Aged; Peripheral Nervous System Diseases; Sural Nerve

Topics: Chondroitin; Chromatography, Gel; Chromatography, Ion Exchange; Electrophoresis, Paper; Epidermolysis Bullosa; Female; Glucuronates; Glycosaminoglycans; Hexosamines; Humans; Hyaluronoglucosaminidase; Spectrophotometry, Infrared; Sulfuric Acids

Topics: Adult; Basement Membrane; Biopsy; Blister; Chondroitin; Epidermolysis Bullosa; Female; Fingers; Histocytochemistry; Humans; Nails; Skin; Staining and Labeling; Sulfates; Toes