Anti-Basement Membrane Autoantibodies in Patients with Anti-Epiligrin Cicatricial Pemphigoid Bind the α Subunit of Laminin 5
| Autor: | R. E. Burgeson, M. P. Marinkovich, G. Kirtschig, Kim B. Yancey |
|---|---|
| Rok vydání: | 1995 |
| Předmět: |
Epidermolysis bullosa acquisita
Adult Keratinocytes Pemphigoid Pathology medicine.medical_specialty medicine.drug_class Pemphigoid Benign Mucous Membrane Dermatology Epidermolysis Bullosa Acquisita Monoclonal antibody Biochemistry Antibodies Basement Membrane Autoimmune Diseases Blister Laminin Antibody Specificity Pemphigoid Bullous medicine Cell Adhesion Humans Lupus Erythematosus Systemic Cicatricial pemphigoid skin and connective tissue diseases Molecular Biology G alpha subunit Autoantibodies biology integumentary system Chemistry Immune Sera Autoantibody Infant Newborn Cell Biology medicine.disease Molecular biology Precipitin Tests Extracellular Matrix Immunoglobulin G biology.protein Bullous pemphigoid Cell Adhesion Molecules |
| Zdroj: | Journal of Investigative Dermatology. 105(4):543-548 |
| ISSN: | 0022-202X |
| DOI: | 10.1111/1523-1747.ep12323431 |
| Popis: | Recent studies have identified a group of cicatricial pemphigoid patients who have IgG anti-basement membrane autoantibodies that recognize epiligrin, a set of disulfide-linked polypeptides closely related if not identical to laminin 5 (formerly called kalinin, nicein, or BM600). To further understand the pathophysiology of blister formation in these patients, we have sought to identify the specific polypeptide(s) targeted by their autoantibodies. Comparative studies show that sera from these patients (nine of nine), P1E1 monoclonal anti-epiligrin antibody, and polyclonal as well as monoclonal anti-laminin 5 antibodies immunoprecipitate the same set of disulfide-linked polypeptides from media of biosynthetically radiolabeled human keratinocytes. Moreover, sera from eight of nine patients with anti-epiligrin cicatricial pemphigoid immunoblot the alpha subunit of laminin 5 but show no reactivity to its beta or gamma subunits. In addition, circulating IgG from a representative patient was affinity-purified against the alpha subunit of laminin 5 and shown to bind the dermal side of 1 M NaC1 split skin in the same manner as autoantibodies from all patients with anti-epiligrin cicatricial pemphigoid. Sera from patients with bullous pemphigoid (n = 5), other forms of cicatricial pemphigoid (n = 5), epidermolysis bullosa acquisita (n = 4), or bullous systemic lupus erythematosus (n = 1) show no reactivity against any subunit of this laminin isoform in immunoprecipitation or immunoblot experiments. These findings correlate with prior reports showing that a monoclonal antibody directed against the alpha subunit of laminin 5 (i.e., laminin subunit alpha 3) induces detachment of human keratinocytes from extracellular matrix in vitro as well as epidermis from human skin in situ. Together, these studies suggest that laminin subunit alpha 3 mediates attachment of basal keratinocytes to epidermal basement membrane and that autoantibodies directed against it may be pathogenic. |
| Databáze: | OpenAIRE |
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