Archives of Dermatological Research

, Volume 280, Issue 6, pp 333–337 | Cite as

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

  • S. Gay
  • J. -D. Fine
  • J. S. Storer
Original Contributions

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.

Key words

Collagen autoantibodies Epidermolysis bullosa Bullous diseases 

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References

  1. 1.
    Bauer EA (1982) Abnormalities in collagenase expression in vitro markers for recessive dystrophic epidermolysis bullosa. J Invest Dermatol 79:105s-108sGoogle Scholar
  2. 2.
    Bauer EA, Eisen AZ (1978) Recessive dystrophic epidermolysis bullosa: evidence for increased collagenase as a genetic characteristic in cell culture. J Exp Med 148:1378–1387Google Scholar
  3. 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 303:776–781Google Scholar
  4. 4.
    Bauer EA, Gedde-Dahl T Jr, Eisen AZ (1977) The role of human skin collagenase in epidermolysis bullosa. J Invest Dermatol 68:119–124Google Scholar
  5. 5.
    Bray JP, Estess F, Bass JA (1969) Anticollagen antibodies following thermal trauma. Proc Soc Exp Biol Med 130:394–398Google Scholar
  6. 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 84:371–373Google Scholar
  7. 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 27:1201–1209Google Scholar
  8. 8.
    Eisen AZ (1969) Human skin collagenase: relationship to the pathogenesis of epidermolysis bullosa dystrophica. J Invest Dermatol 52:449–453Google Scholar
  9. 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 82:35–38Google Scholar
  10. 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 42:336–342Google Scholar
  11. 11.
    Furthmayr H (ed) (1982) Immunochemistry of the extracellular matrix, vols 1,2. CRC Press, Boca RatonGoogle Scholar
  12. 12.
    Furuto DK, Miller EJ (1980) Isolation of a unique collagenous fraction from limited pepsin digests of human placental tissue. J Biol Chem 255:290–295Google Scholar
  13. 13.
    Gay S, Fine J-D (1987) Immunization, isolation and characterization of polyclonal and monoclonal antibodies against collagens for use in immunohistochemistry. Methods Enzymol 145:148–167Google Scholar
  14. 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 269–288Google Scholar
  15. 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 198:370–378Google Scholar
  16. 16.
    Gay S, Miller EJ (1983) What is collagen, and what is not. Ultrastruct Pathol 4:365–377Google Scholar
  17. 17.
    Gay S, Ward WQ, Gay R, Miller EJ (1980) Autoantibodies to basement membrane collage: epidermolysis bullosa versus bullous pemphigoid. J Cutan Pathol 7:315–317Google Scholar
  18. 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 76:113–118Google Scholar
  19. 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 18:3089–3097Google Scholar
  20. 20.
    Lazarus GS (1972) Collagenase and connective tissue metabolism in epidermolysis bullosa. J Invest Dermatol 58:242–248Google Scholar
  21. 21.
    Mackel AM, DeLustro F, Harper FE, LeRoy EC (1982) Antibodies to collagen in scleroderma. Arthritis Rheum 25:522–531Google Scholar
  22. 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 47:247–257Google Scholar
  23. 23.
    Miller EJ (1972) Structural studies on cartilage collagen employing limited cleavage and solubilization with pepsin. Biochemistry 11:4903–4909Google Scholar
  24. 24.
    Miller EJ, Gay S (1987) Collagens. Methods Enzymol 144:3–41Google Scholar
  25. 25.
    Miller EJ, Rhodes RK (1982) Preparation and characterization of the different types of collagen. Methods Enzymol 82A:33–64Google Scholar
  26. 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 304:197–204Google Scholar
  27. 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 69:1373–1383Google Scholar
  28. 28.
    Timpl R (1982) Antibodies to collagens and procollagens. Methods Enzymol 82A:472–498Google Scholar
  29. 29.
    Timpl R (1984) Immunology of the collagens. In: Piez KA, Reddi AH (eds) Extracellular matrix biochemistry. Elsevier, New York, pp 159–190Google Scholar
  30. 30.
    Valle K-J, Bauer EA (1980) Enhanced biosynthesis of human skin collagenase in fibroblast cultures from recessive dystrophic epidermolysis bullosa. J Clin Invest 66:176–187Google Scholar
  31. 31.
    Watson RF, Rothbard S, Vanamee P (1954) The antigenicity of rat collagen. J Exp Med 99:535–548Google Scholar

Copyright information

© Springer-Verlag 1988

Authors and Affiliations

  • S. Gay
    • 1
    • 2
  • J. -D. Fine
    • 1
    • 3
    • 2
  • J. S. Storer
    • 4
  1. 1.Department of Medicine, Institute of Dental ResearchUniversity of Alabama at BirminghamBirminghamUSA
  2. 2.Department of Dermatology, Institute of Dental ResearchUniversity of Alabama at BirminghamBirminghamUSA
  3. 3.Dermatology SectionMedical Service and Birmingham Veterans Administration Medical CenterBirminghamUSA
  4. 4.Department of DermatologyTulane University School of MedicineNew OrleansUSA

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