Type VII collagen/Autoimmunity

Autoimmune diseases a characterized by a misled response to endogenous proteins. Why an endogenous protein present in the human body for a long time is suddenly recognized as exogenous is not yet understood.

Epidermolysis bullosa acquisita (EBA) is an autoimmune disease of the skin which is characterized by autoantibodies directed against type VII collagen. Type VII collagen links different skin layers together. Autoantibody binding to type VII collagen results in skin blistering and skin lesions.

Our group has characterized interactions of type VII collagen subdomains with e.g. other extracellular matrix proteins [1, 2]. We could show that type VII collagen has a cystine knot with an hitherto unknown topology [3] and that the hinge region of type VII collagen is intrinsically disordered [4]. We recently showed that a mutation in a type VII collagen subdomain results in thermolability of this domain which renders it susceptible to proteases [5].



  1. Wegener H, Leineweber S, Seeger K. The vWFA2 domain of type VII collagen is responsible for collagen binding. Biochem Biophys Res Commun 2013, 430(2): 449-453. DOI: 10.1016/j.bbrc.2012.11.119
  2. Leineweber S, Schönig S, Seeger K. Insight into interactions of the von-Willebrand factor-A-like domain 2 with the FNIII like domain 9 of collagen VII by NMR and SPR. FEBS Lett 2011, 585: 1748-1752. DOI: 10.1016/j.febslet.2011.04.071
  3. Wegener H, Paulsen H, Seeger K. The cysteine rich region of type VII collagen is a cystine knot with a new topology. J Biol Chem. 2014, 289(8): 4861-4869. DOI: 10.1074/jbc.M113.531327
  4. Richer BC, Seeger K.: The hinge region of type VII collagen is intrinsically disordered. Matrix Biol. 2014, 36: 77-83. DOI: 10.1016/j.matbio.2014.04.006
  5. Windler C, Hermsdorf U, Brinckmann J, Seeger K.: A type VII collagen subdomain mutant is thermolabile and shows enhanced proteolytic degradability – implications for the pathogenesis of recessive dystrophic epidermolysis bullosa?, Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 2017 1863: 52-59. DOI: 10.1016/j.bbadis.2016.10.023


Further literature on type VII collagen

  • Hermsdorf U, Seeger K.: Chemical shift assignments of the fibronectin III like domains 7-8 of type VII collagen. Biomol NMR Assign 2016 10: 53-55. DOI: 10.1007/s12104-015-9636-9
  • Iwata H, Witte M, Samavedam UK, Gupta Y, Shimizu A, Ishiko A, Schröder T, Seeger K, Dahlke M, Rades D, Zillikens D, Ludwig RJ.: Radiosensitive hematopoietic cells determine the extent of skin inflammation in experimental epidermolysis bullosa acquisita. J Immunol. 2015, 195(5):1945-54. DOI: 10.4049/jimmunol.1501003
  • Iwata H, Bieber K, Tiburzy B, Chrobok N, Kalies K, Shimizu A, Leineweber S, Ishiko A, Vorobyev A, Zillikens D, K hl J, Westermann J, Seeger K, Manz R, Ludwig RJ.: B Cells, Dendritic Cells, and Macrophages Are required to induce an autoreactive CD4 helper T cell response in experimental epidermolysis bullosa acquisita. J Immunol. 2013, 191(6): 2978-2988. DOI: 10.4049/jimmunol.1300310
  • Schönig S, Recke A, Hirose M, Ludwig R, Seeger K.: Metabolite analysis distinguishes between mice with epidermolysis bullosa acquisita and healthy mice. Orphanet Journal of Rare Diseases 2013, 8(1):93. DOI: 10.1186/1750-1172-8-93