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Normal human skin is superior to monkey oesophagus substrate for detection of circulating BP180-NC16A-specific IgG antibodies in bullous pemphigoid.
Br J Dermatol. 2019 05; 180(5):1099-1106.BJ

Abstract

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.

Authors+Show Affiliations

Lübeck Institute of Experimental Dermatology (LIED), University of Lübeck, Lübeck, Germany.Department of Dermatology, University of Pennsylvania, Philadelphia, PA, U.S.A. Department of Dermatology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.Department of Dermatology, University of Pennsylvania, Philadelphia, PA, U.S.A.Department of Dermatology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.Lübeck Institute of Experimental Dermatology (LIED), University of Lübeck, Lübeck, Germany.Lübeck Institute of Experimental Dermatology (LIED), University of Lübeck, Lübeck, Germany. Departement of Dermatology, University of Lübeck, Lübeck, Germany.Institute of Experimental Immunology, EUROIMMUN, Lübeck, Germany.Department of Dermatology, University of Pennsylvania, Philadelphia, PA, U.S.A.Lübeck Institute of Experimental Dermatology (LIED), University of Lübeck, Lübeck, Germany. Department of Dermatology, University of Pennsylvania, Philadelphia, PA, U.S.A. Departement of Dermatology, University of Lübeck, Lübeck, Germany.

Pub Type(s)

Comparative Study
Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

30315657

Citation

Emtenani, S, et al. "Normal Human Skin Is Superior to Monkey Oesophagus Substrate for Detection of Circulating BP180-NC16A-specific IgG Antibodies in Bullous Pemphigoid." The British Journal of Dermatology, vol. 180, no. 5, 2019, pp. 1099-1106.
Emtenani S, Yuan H, Lin C, et al. Normal human skin is superior to monkey oesophagus substrate for detection of circulating BP180-NC16A-specific IgG antibodies in bullous pemphigoid. Br J Dermatol. 2019;180(5):1099-1106.
Emtenani, S., Yuan, H., Lin, C., Pan, M., Hundt, J. E., Schmidt, E., Komorowski, L., Stanley, J. R., & Hammers, C. M. (2019). Normal human skin is superior to monkey oesophagus substrate for detection of circulating BP180-NC16A-specific IgG antibodies in bullous pemphigoid. The British Journal of Dermatology, 180(5), 1099-1106. https://doi.org/10.1111/bjd.17313
Emtenani S, et al. Normal Human Skin Is Superior to Monkey Oesophagus Substrate for Detection of Circulating BP180-NC16A-specific IgG Antibodies in Bullous Pemphigoid. Br J Dermatol. 2019;180(5):1099-1106. PubMed PMID: 30315657.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Normal human skin is superior to monkey oesophagus substrate for detection of circulating BP180-NC16A-specific IgG antibodies in bullous pemphigoid. AU - Emtenani,S, AU - Yuan,H, AU - Lin,C, AU - Pan,M, AU - Hundt,J E, AU - Schmidt,E, AU - Komorowski,L, AU - Stanley,J R, AU - Hammers,C M, Y1 - 2019/01/01/ PY - 2018/10/06/accepted PY - 2018/10/14/pubmed PY - 2020/7/4/medline PY - 2018/10/14/entrez SP - 1099 EP - 1106 JF - The British journal of dermatology JO - Br J Dermatol VL - 180 IS - 5 N2 - 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. SN - 1365-2133 UR - https://www.unboundmedicine.com/medline/citation/30315657/Normal_human_skin_is_superior_to_monkey_oesophagus_substrate_for_detection_of_circulating_BP180_NC16A_specific_IgG_antibodies_in_bullous_pemphigoid_ L2 - https://doi.org/10.1111/bjd.17313 DB - PRIME DP - Unbound Medicine ER -