Normal human skin is superior to monkey oesophagus substrate for detection of circulating BP180-NC16A-specific IgG antibodies in bullous pemphigoid.
Adult
Aged
Aged, 80 and over
Animals
Antibodies, Monoclonal
/ blood
Autoantibodies
/ blood
Autoantigens
/ immunology
Epitopes
/ immunology
Esophagus
/ immunology
Female
Fluorescent Antibody Technique, Indirect
/ methods
Haplorhini
Humans
Immunoglobulin G
/ blood
Male
Middle Aged
Non-Fibrillar Collagens
/ immunology
Pemphigoid, Bullous
/ blood
Protein Domains
/ immunology
Skin
/ immunology
Collagen Type XVII
Journal
The British journal of dermatology
ISSN: 1365-2133
Titre abrégé: Br J Dermatol
Pays: England
ID NLM: 0004041
Informations de publication
Date de publication:
05 2019
05 2019
Historique:
accepted:
06
10
2018
pubmed:
14
10
2018
medline:
4
7
2020
entrez:
14
10
2018
Statut:
ppublish
Résumé
Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering skin disease. Two antigens have been identified as targets of circulating autoantibodies (autoAbs) - BP180 and BP230 - with BP180 being a critical transmembrane adhesion protein of basal keratinocytes of the epidermis. The noncollagenous domain 16A (NC16A) of BP180 is the immunodominant epitope in patients with BP, and anti-BP180-NC16A IgG antibodies (Abs) correlate to disease activity. Routine serological testing and follow-up of BP relies on indirect immunofluorescence (IIF) of serum Abs, commonly performed on monkey oesophagus (ME), and/or enzyme-linked immunosorbent assay (ELISA) testing on recombinantly produced fragments of BP180 and BP230 (BP180-NC16A, BP230-C/N). To determine if NC16A epitopes are well represented on ME substrate. Sera from different BP cohorts were tested by IIF on ME and normal human skin (NHS). To confirm findings, affinity-purified anti-BP180-NC16A/BP230 polyclonal Abs and recombinant anti-BP180-NC16A/BP230 monoclonal antibodies (mAbs) were used. For sensitive detection of BP180-NC16A-specific IgG Abs, sections of NHS are superior to the widely used ME. Confirmation comes from polyclonal affinity-purified anti-BP180-NC16A/BP230 Abs, and by mAbs cloned from a patient with active BP. Use of NHS is preferable over ME in routine IIF testing for BP. These results are of clinical relevance because anti-BP180-NC16A IgG titres are correlated to disease activity and detecting them reliably is important for screening, diagnosis and follow-up of patients with BP.
Sections du résumé
BACKGROUND
Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering skin disease. Two antigens have been identified as targets of circulating autoantibodies (autoAbs) - BP180 and BP230 - with BP180 being a critical transmembrane adhesion protein of basal keratinocytes of the epidermis. The noncollagenous domain 16A (NC16A) of BP180 is the immunodominant epitope in patients with BP, and anti-BP180-NC16A IgG antibodies (Abs) correlate to disease activity. Routine serological testing and follow-up of BP relies on indirect immunofluorescence (IIF) of serum Abs, commonly performed on monkey oesophagus (ME), and/or enzyme-linked immunosorbent assay (ELISA) testing on recombinantly produced fragments of BP180 and BP230 (BP180-NC16A, BP230-C/N).
OBJECTIVES
To determine if NC16A epitopes are well represented on ME substrate.
METHODS
Sera from different BP cohorts were tested by IIF on ME and normal human skin (NHS). To confirm findings, affinity-purified anti-BP180-NC16A/BP230 polyclonal Abs and recombinant anti-BP180-NC16A/BP230 monoclonal antibodies (mAbs) were used.
RESULTS
For sensitive detection of BP180-NC16A-specific IgG Abs, sections of NHS are superior to the widely used ME. Confirmation comes from polyclonal affinity-purified anti-BP180-NC16A/BP230 Abs, and by mAbs cloned from a patient with active BP.
CONCLUSIONS
Use of NHS is preferable over ME in routine IIF testing for BP. These results are of clinical relevance because anti-BP180-NC16A IgG titres are correlated to disease activity and detecting them reliably is important for screening, diagnosis and follow-up of patients with BP.
Identifiants
pubmed: 30315657
doi: 10.1111/bjd.17313
pmc: PMC6462259
mid: NIHMS992646
doi:
Substances chimiques
Antibodies, Monoclonal
0
Autoantibodies
0
Autoantigens
0
Epitopes
0
Immunoglobulin G
0
Non-Fibrillar Collagens
0
Types de publication
Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1099-1106Subventions
Organisme : NIAMS NIH HHS
ID : R01 AR052672
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2018 British Association of Dermatologists.
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