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Autoantibodies to extracellular collagen matrix components in epidermolysis bullosa and other bullous diseases

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Summary

In order to determine whether autoantibodies are present in sera from normal individuals and/or patients with selected bullous disorders, a highly sensitive solid-phase radioimmune assay was established using purified native collagen types I–VI, laminin, and fibronectin as substrates. Sixty-four sera were utilized, representing 12 normal controls as well as 4 patients with extensive thermal burns, 18 with autoimmune bullous diseases (11 bullous pemphigoid, 5 pemphigus vulgaris, and 2 epidermolysis bullosa acquisita), and 30 with non-autoimmune mechanobullous diseases [epidermolysis bullosa (EB): 20 simplex, 4 junctional, and 6 dystrophic]. In general, autoantibodies to types I, II, and VI collagen and fibronectin were undetectable in any of the patient or control groups. In contrast, autoantibodies to types III and V collagen were noted in 87.5% (28/32) and 90.6% (29/32) of EB sera, respectively, while being only rarely noted in sera from other patient groups. Similarly, autoantibodies to type IV collagen and laminin were detected in 50% (16/32) and 40.6% (13/32) of EB sera, especially from patients with simplex and dystrophic forms of the disease. These data suggest that selected interstitial and basement membrane-associated collagens and laminin may become autoimmunogenic in all three forms of inherited EB in contrast to their relative lack of immunogenicity in at least some of the other intraepidermal and subepidermal blistering disorders. The role, if any, of these autoantibodies in the induction or perpetuation of blistering in EB awaits further studies.

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References

  1. Bauer EA (1982) Abnormalities in collagenase expression in vitro markers for recessive dystrophic epidermolysis bullosa. J Invest Dermatol 79:105s-108s

    Google Scholar 

  2. Bauer EA, Eisen AZ (1978) Recessive dystrophic epidermolysis bullosa: evidence for increased collagenase as a genetic characteristic in cell culture. J Exp Med 148:1378–1387

    Google Scholar 

  3. Bauer EA, Cooper TW, Tucker DR, Esterly NB (1980) Phenytoin therapy of recessive dystrophic epidermolysis bullosa. Clinical trial and proposed mechanism of action on collagenase. N Engl J Med 303:776–781

    Google Scholar 

  4. Bauer EA, Gedde-Dahl T Jr, Eisen AZ (1977) The role of human skin collagenase in epidermolysis bullosa. J Invest Dermatol 68:119–124

    Google Scholar 

  5. Bray JP, Estess F, Bass JA (1969) Anticollagen antibodies following thermal trauma. Proc Soc Exp Biol Med 130:394–398

    Google Scholar 

  6. Briggaman RA (1985) Is there any specificity to defects of anchoring fibrils in epidermolysis bullosa dystrophica, and what does this mean in terms of pathogenesis? J Invest Dermatol 84:371–373

    Google Scholar 

  7. Collier DH, Derwar SS, Garovoy M, Fye KH, Stobo JD (1984) Anti-collagen antibodies and immune response gene products in rheumatoid arthritis. Arthritis Rheum 27:1201–1209

    Google Scholar 

  8. Eisen AZ (1969) Human skin collagenase: relationship to the pathogenesis of epidermolysis bullosa dystrophica. J Invest Dermatol 52:449–453

    Google Scholar 

  9. Fine J-D, Breathnach SM, Hintner H, Katz SI (1984) KF-1 monoclonal antibody defines a specific basement membrane antigen defect in dystrophic forms of epidermolysis bullosa. J Invest Dermatol 82:35–38

    Google Scholar 

  10. Foidart J-M, Bere E, Yaar M, Rennard S, Gullino M, Martin G, Katz S (1980) Distribution and immunoelectron microscopic localization of laminin, a non-collagenous basement membrane glycoprotein. Lab Invest 42:336–342

    Google Scholar 

  11. Furthmayr H (ed) (1982) Immunochemistry of the extracellular matrix, vols 1,2. CRC Press, Boca Raton

    Google Scholar 

  12. Furuto DK, Miller EJ (1980) Isolation of a unique collagenous fraction from limited pepsin digests of human placental tissue. J Biol Chem 255:290–295

    Google Scholar 

  13. Gay S, Fine J-D (1987) Immunization, isolation and characterization of polyclonal and monoclonal antibodies against collagens for use in immunohistochemistry. Methods Enzymol 145:148–167

    Google Scholar 

  14. Gay S, Kresina TF (1982) Immunological disorders of collagen. In: Jayson MIV, Weiss JB (eds) Collagen in health and disease. Churchill Livingston, Edinburgh, pp 269–288

    Google Scholar 

  15. Gay S, Miller EJ (1979) Characterization of lens capsule collagen: evidence for the presence of two unique chains in molecules derived from major basement membrane structures. Arch Biochem Biophys 198:370–378

    Google Scholar 

  16. Gay S, Miller EJ (1983) What is collagen, and what is not. Ultrastruct Pathol 4:365–377

    Google Scholar 

  17. Gay S, Ward WQ, Gay R, Miller EJ (1980) Autoantibodies to basement membrane collage: epidermolysis bullosa versus bullous pemphigoid. J Cutan Pathol 7:315–317

    Google Scholar 

  18. Hintner H, Stingl G, Schuler G, Fritsch P, Stanley J, Katz S, Wolff K (1981) Immunofluorescence mapping of antigenic determinants within the dermal-epidermal junction in mechanobullous diseases. J Invest Dermatol 76:113–118

    Google Scholar 

  19. Kresina TF, Miller EJ (1979) Isolation and characterization of basement membrane collagen from human placental tissue. Evidence for the presence of two genetically distinct collagen chains. Biochemistry 18:3089–3097

    Google Scholar 

  20. Lazarus GS (1972) Collagenase and connective tissue metabolism in epidermolysis bullosa. J Invest Dermatol 58:242–248

    Google Scholar 

  21. Mackel AM, DeLustro F, Harper FE, LeRoy EC (1982) Antibodies to collagen in scleroderma. Arthritis Rheum 25:522–531

    Google Scholar 

  22. Martinez-Hernandez A, Miller EJ, Damjanov I, Gay S (1982) Biochemical and electron immunohistochemical studies of a rat parietal yolk sac carcinoma that secretes laminin. Lab Invest 47:247–257

    Google Scholar 

  23. Miller EJ (1972) Structural studies on cartilage collagen employing limited cleavage and solubilization with pepsin. Biochemistry 11:4903–4909

    Google Scholar 

  24. Miller EJ, Gay S (1987) Collagens. Methods Enzymol 144:3–41

    Google Scholar 

  25. Miller EJ, Rhodes RK (1982) Preparation and characterization of the different types of collagen. Methods Enzymol 82A:33–64

    Google Scholar 

  26. Savolainen E-R, Kero M, Pihlajaniemi T, Kivirikko KI (1981) Deficiency of galactosylhydroxylysyl glucosyltransferase, an enzyme of collagen synthesis, in a family with dominant epidermolysis bullosa simplex. N Engl J Med 304:197–204

    Google Scholar 

  27. Stricklin GP, Welgus HG, Bauer EA (1982) Human skin collagenase in recessive dystrophic epidermolysis bullosa. Purification of a mutant enzyme from fibroblast cultures. J Clin Invest 69:1373–1383

    Google Scholar 

  28. Timpl R (1982) Antibodies to collagens and procollagens. Methods Enzymol 82A:472–498

    Google Scholar 

  29. Timpl R (1984) Immunology of the collagens. In: Piez KA, Reddi AH (eds) Extracellular matrix biochemistry. Elsevier, New York, pp 159–190

    Google Scholar 

  30. Valle K-J, Bauer EA (1980) Enhanced biosynthesis of human skin collagenase in fibroblast cultures from recessive dystrophic epidermolysis bullosa. J Clin Invest 66:176–187

    Google Scholar 

  31. Watson RF, Rothbard S, Vanamee P (1954) The antigenicity of rat collagen. J Exp Med 99:535–548

    Google Scholar 

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Supported in part by grant DE 02670 from the National Institute of Dental Research (SG), grants AR 34861 and AR 36629 from the National Institute of Arthritis, Musculoskeletal, and Skin Diseases (JDF) and by the Medical Research Service of the Veterans Administration (JDF)

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Gay, S., Fine, J.D. & Storer, J.S. Autoantibodies to extracellular collagen matrix components in epidermolysis bullosa and other bullous diseases. Arch Dermatol Res 280, 333–337 (1988). https://doi.org/10.1007/BF00426610

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  • DOI: https://doi.org/10.1007/BF00426610

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