Bullous pemphigoid antigen 1 isoforms: potential new target autoantigens in multiple sclerosis?

• Published in: British journal of dermatology (1951) Vol. 152; no. 3; pp. 537 - 540
• Main Authors: Laffitte, E., Burkhard, P.R., Fontao, L., Jaunin, F., Saurat, J-H., Chofflon, M., Borradori, L.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01-03-2005; Blackwell; Oxford University Press
• Subjects: Autoantibodies - cerebrospinal fluid; autoantibody; Autoantigens - immunology; Biological and medical sciences; Bullous diseases of the skin; bullous pemphigoid; bullous pemphigoid antigen 1; Carrier Proteins - genetics; Carrier Proteins - immunology; Cytoskeletal Proteins - genetics; Cytoskeletal Proteins - immunology; Dermatology; Dystonin; epitope-spreading phenomenon; Glutathione Transferase - immunology; Humans; Medical sciences; multiple sclerosis; Multiple Sclerosis - immunology; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - immunology; Neurology; Pemphigoid, Bullous - immunology; Protein Isoforms - immunology; Recombinant Proteins - immunology; Bullous dermatosis; Autoimmunity; Human; dystonin; Skin disease; Nervous system diseases; Multiple sclerosis; Antigenic determinant; Dermatology; Autoantibody; Autoimmune disease; Inflammatory disease; Autoantigen; Bullous pemphigoid; Central nervous system disease; bullous pemphigoid antigen 1; epitope-spreading phenomenon
• ISSN: 0007-0963; 1365-2133
• DOI: 10.1111/j.1365-2133.2004.06338.x

Summary
Background  The simultaneous occurrence of bullous pemphigoid (BP) and multiple sclerosis (MS), two autoimmune diseases involving the skin and the central nervous system (CNS), respectively, has been described.
Objectives  As the BPAG1 gene encodes the epithelial isoform of BP antigen 1 (BPAG1‐e), a major autoantigen of BP, as well as additional variants expressed in the neurones of the CNS and peripheral nervous system and in Schwann cells, we tested the hypothesis that products of the BPAG1 gene act as shared autoantigens in both BP and MS.
Methods  The reactivity of cerebrospinal fluid (CSF) obtained from 18 patients with MS, 10 patients with other inflammatory CNS diseases and 20 normal controls was assayed by immunoblotting against two recombinant fragments of BPAG1‐e encompassing regions that are also found in the neuronal variants BPAG1‐n and BPAG1‐a.
Results  The recombinant protein glutathione‐S‐transferase (GST)‐BPAG1‐e1−887 was recognized by five of 18 (27%) CSF samples obtained from patients with MS, two of 10 (20%) samples from patients with other inflammatory neurological diseases and five of 20 (25%) samples from normal controls. Furthermore, two of 18 (11%) CSF samples from patients with MS bound to GST‐BPAG1‐e1880−2649, whereas none of the samples obtained from patients with other inflammatory neurological diseases or from control subjects showed reactivity.
Conclusions  These results raise the possibility that a subset of patients with MS develops an autoantibody response to the neuronal variants of BPAG1. These findings potentially open the avenue of neuronal BPAG1 variants being novel targets of autoantibodies in neurological diseases.