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Sensitive and specific assay for the serological diagnosis of anti-p200 pemphigoid based on the recombinant laminin β4 subunit.

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Technique of Conjunctival Biopsy and Direct Immunofluorescence for Diagnosing Mucous Membrane Pemphigoid
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Anti-p200 pemphigoid.

Stephanie Goletz1, Takashi Hashimoto2, Detlef Zillikens1

  • 1Department of Dermatology, University of Luebeck, Luebeck, Germany.

Journal of the American Academy of Dermatology
|April 29, 2014
PubMed
Summary
This summary is machine-generated.

Anti-p200 pemphigoid autoantibodies target laminin γ1, aiding diagnosis of this rare blistering skin disease. However, these antibodies may not be the primary cause, suggesting other autoantigens are involved.

Keywords:
anti-p200 pemphigoidautoantibodyautoantigenlaminin γ1p200 antigensubepidermal blistering skin disease

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Area of Science:

  • Dermatology
  • Immunology
  • Autoimmune Blistering Diseases

Background:

  • Anti-p200 pemphigoid is a rare subepidermal blistering skin disease.
  • Clinical presentation resembles bullous pemphigoid and epidermolysis bullosa acquisita.
  • Autoantibodies in patients recognize a 200-kd protein at the dermal-epidermal junction.

Purpose of the Study:

  • To investigate the autoantigen recognized by anti-p200 pemphigoid autoantibodies.
  • To determine the diagnostic utility of anti-laminin γ1 antibodies.
  • To explore the pathogenic role of anti-laminin γ1 antibodies in anti-p200 pemphigoid.

Main Methods:

  • Indirect immunofluorescence microscopy on NaCl-split human skin.
  • Immunoblotting of human dermal extract and recombinant laminin γ1 C-terminus.
  • Enzyme-linked immunosorbent assay (ELISA) for serologic diagnosis.
  • Ex vivo and in vivo studies of autoantibody-mediated skin splitting.

Main Results:

  • 90% of anti-p200 pemphigoid sera recognized laminin γ1, with the C-terminus being immunodominant.
  • Recombinant laminin γ1 C-terminus facilitated serologic diagnosis.
  • Anti-laminin γ1 antibodies alone did not demonstrate pathogenic activity in ex vivo models.
  • Both patient sera and anti-laminin γ1 depleted sera induced skin splitting via leukocyte-dependent neutrophil activation.

Conclusions:

  • Anti-laminin γ1 antibodies are valuable diagnostic biomarkers for anti-p200 pemphigoid.
  • The pathogenic autoantigen in anti-p200 pemphigoid remains to be fully elucidated.
  • The true autoantigen may be an unknown laminin γ1 isoform or another 200-kd protein.