IgG anti-laminin-332 autoantibodies are present in a subset of patients with mucous membrane, but not bullous, pemphigoid

Zelmira Lazarova, Valerie K. Salato, Christoph M. Lanschuetzer, Marleen Janson, Janet A. Fairley, Kim B. Yancey

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Abstract

Background: Antiepiligrin cicatricial pemphigoid is a mucosal-predominant subepidermal blistering disease associated with an increased relative risk of cancer. In contrast to prior reports showing that anti-laminin (L)-332 autoantibodies are a reliable marker for patients with antiepiligrin cicatricial pemphigoid, a recent report suggested that as many as 40% of patients with bullous pemphigoid (BP) have IgG reactive with this laminin isoform. Objective: We sought to determine whether patients with BP possess circulating IgG anti-L-332 autoantibodies. Methods: Sera from 100 adults with BP were analyzed by indirect immunofluorescence testing of intact skin, immunoblot studies of human keratinocyte (HK) extracts, and a new L-332 enzyme-linked immunosorbent assay. Sera showing reactivity suggestive of anti-L-332 autoantibodies in these assays were further analyzed in immunoblot studies of HK extracellular matrix and immunoprecipitation studies of biosynthetically radiolabeled HK extracts. Results: IgG from all patients with BP bound intact epidermal basement membrane by indirect immunofluorescence microscopy and immunoblotted bullous pemphigoid antigen-1, -2, or both in HK extracts. None of these sera immunoblotted L-332 in HK extracts, although 13 did score above the cut point of a new IgG4 L-332 enzyme-linked immunosorbent assay (sensitivity = 0.91, specificity = 0.98, Youden index = 0.89). Further analysis of sera from these 13 patients found: (1) all had IgG that bound the epidermal side of 1 mol/L NaCl split skin by indirect immunofluorescence microscopy; (2) none immunoblotted L-332 purified from HK extracellular matrix; and (3) none immunoprecipitated L-332 from biosynthetically radiolabeled HK extracts. Limitations: The basis of false-positive enzyme-linked immunosorbent assay determinations for anti-L-332 IgG among patients with BP is unknown. Conclusion: Anti-L-332 autoantibodies remain a reliable marker for patients with antiepiligrin cicatricial pemphigoid.

Original languageEnglish (US)
Pages (from-to)951-958
Number of pages8
JournalJournal of the American Academy of Dermatology
Volume58
Issue number6
DOIs
StatePublished - Jun 2008

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Bullous Pemphigoid
Keratinocytes
Autoantibodies
Mucous Membrane
Benign Mucous Membrane Pemphigoid
Immunoglobulin G
Indirect Fluorescent Antibody Technique
Enzyme-Linked Immunosorbent Assay
Serum
Fluorescence Microscopy
Extracellular Matrix
Skin
Laminin
kalinin
anti-IgG
Immunoprecipitation
Basement Membrane
Protein Isoforms
Sensitivity and Specificity

ASJC Scopus subject areas

  • Dermatology

Cite this

IgG anti-laminin-332 autoantibodies are present in a subset of patients with mucous membrane, but not bullous, pemphigoid. / Lazarova, Zelmira; Salato, Valerie K.; Lanschuetzer, Christoph M.; Janson, Marleen; Fairley, Janet A.; Yancey, Kim B.

In: Journal of the American Academy of Dermatology, Vol. 58, No. 6, 06.2008, p. 951-958.

Research output: Contribution to journalArticle

Lazarova, Zelmira ; Salato, Valerie K. ; Lanschuetzer, Christoph M. ; Janson, Marleen ; Fairley, Janet A. ; Yancey, Kim B. / IgG anti-laminin-332 autoantibodies are present in a subset of patients with mucous membrane, but not bullous, pemphigoid. In: Journal of the American Academy of Dermatology. 2008 ; Vol. 58, No. 6. pp. 951-958.
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abstract = "Background: Antiepiligrin cicatricial pemphigoid is a mucosal-predominant subepidermal blistering disease associated with an increased relative risk of cancer. In contrast to prior reports showing that anti-laminin (L)-332 autoantibodies are a reliable marker for patients with antiepiligrin cicatricial pemphigoid, a recent report suggested that as many as 40{\%} of patients with bullous pemphigoid (BP) have IgG reactive with this laminin isoform. Objective: We sought to determine whether patients with BP possess circulating IgG anti-L-332 autoantibodies. Methods: Sera from 100 adults with BP were analyzed by indirect immunofluorescence testing of intact skin, immunoblot studies of human keratinocyte (HK) extracts, and a new L-332 enzyme-linked immunosorbent assay. Sera showing reactivity suggestive of anti-L-332 autoantibodies in these assays were further analyzed in immunoblot studies of HK extracellular matrix and immunoprecipitation studies of biosynthetically radiolabeled HK extracts. Results: IgG from all patients with BP bound intact epidermal basement membrane by indirect immunofluorescence microscopy and immunoblotted bullous pemphigoid antigen-1, -2, or both in HK extracts. None of these sera immunoblotted L-332 in HK extracts, although 13 did score above the cut point of a new IgG4 L-332 enzyme-linked immunosorbent assay (sensitivity = 0.91, specificity = 0.98, Youden index = 0.89). Further analysis of sera from these 13 patients found: (1) all had IgG that bound the epidermal side of 1 mol/L NaCl split skin by indirect immunofluorescence microscopy; (2) none immunoblotted L-332 purified from HK extracellular matrix; and (3) none immunoprecipitated L-332 from biosynthetically radiolabeled HK extracts. Limitations: The basis of false-positive enzyme-linked immunosorbent assay determinations for anti-L-332 IgG among patients with BP is unknown. Conclusion: Anti-L-332 autoantibodies remain a reliable marker for patients with antiepiligrin cicatricial pemphigoid.",
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T1 - IgG anti-laminin-332 autoantibodies are present in a subset of patients with mucous membrane, but not bullous, pemphigoid

AU - Lazarova, Zelmira

AU - Salato, Valerie K.

AU - Lanschuetzer, Christoph M.

AU - Janson, Marleen

AU - Fairley, Janet A.

AU - Yancey, Kim B.

PY - 2008/6

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N2 - Background: Antiepiligrin cicatricial pemphigoid is a mucosal-predominant subepidermal blistering disease associated with an increased relative risk of cancer. In contrast to prior reports showing that anti-laminin (L)-332 autoantibodies are a reliable marker for patients with antiepiligrin cicatricial pemphigoid, a recent report suggested that as many as 40% of patients with bullous pemphigoid (BP) have IgG reactive with this laminin isoform. Objective: We sought to determine whether patients with BP possess circulating IgG anti-L-332 autoantibodies. Methods: Sera from 100 adults with BP were analyzed by indirect immunofluorescence testing of intact skin, immunoblot studies of human keratinocyte (HK) extracts, and a new L-332 enzyme-linked immunosorbent assay. Sera showing reactivity suggestive of anti-L-332 autoantibodies in these assays were further analyzed in immunoblot studies of HK extracellular matrix and immunoprecipitation studies of biosynthetically radiolabeled HK extracts. Results: IgG from all patients with BP bound intact epidermal basement membrane by indirect immunofluorescence microscopy and immunoblotted bullous pemphigoid antigen-1, -2, or both in HK extracts. None of these sera immunoblotted L-332 in HK extracts, although 13 did score above the cut point of a new IgG4 L-332 enzyme-linked immunosorbent assay (sensitivity = 0.91, specificity = 0.98, Youden index = 0.89). Further analysis of sera from these 13 patients found: (1) all had IgG that bound the epidermal side of 1 mol/L NaCl split skin by indirect immunofluorescence microscopy; (2) none immunoblotted L-332 purified from HK extracellular matrix; and (3) none immunoprecipitated L-332 from biosynthetically radiolabeled HK extracts. Limitations: The basis of false-positive enzyme-linked immunosorbent assay determinations for anti-L-332 IgG among patients with BP is unknown. Conclusion: Anti-L-332 autoantibodies remain a reliable marker for patients with antiepiligrin cicatricial pemphigoid.

AB - Background: Antiepiligrin cicatricial pemphigoid is a mucosal-predominant subepidermal blistering disease associated with an increased relative risk of cancer. In contrast to prior reports showing that anti-laminin (L)-332 autoantibodies are a reliable marker for patients with antiepiligrin cicatricial pemphigoid, a recent report suggested that as many as 40% of patients with bullous pemphigoid (BP) have IgG reactive with this laminin isoform. Objective: We sought to determine whether patients with BP possess circulating IgG anti-L-332 autoantibodies. Methods: Sera from 100 adults with BP were analyzed by indirect immunofluorescence testing of intact skin, immunoblot studies of human keratinocyte (HK) extracts, and a new L-332 enzyme-linked immunosorbent assay. Sera showing reactivity suggestive of anti-L-332 autoantibodies in these assays were further analyzed in immunoblot studies of HK extracellular matrix and immunoprecipitation studies of biosynthetically radiolabeled HK extracts. Results: IgG from all patients with BP bound intact epidermal basement membrane by indirect immunofluorescence microscopy and immunoblotted bullous pemphigoid antigen-1, -2, or both in HK extracts. None of these sera immunoblotted L-332 in HK extracts, although 13 did score above the cut point of a new IgG4 L-332 enzyme-linked immunosorbent assay (sensitivity = 0.91, specificity = 0.98, Youden index = 0.89). Further analysis of sera from these 13 patients found: (1) all had IgG that bound the epidermal side of 1 mol/L NaCl split skin by indirect immunofluorescence microscopy; (2) none immunoblotted L-332 purified from HK extracellular matrix; and (3) none immunoprecipitated L-332 from biosynthetically radiolabeled HK extracts. Limitations: The basis of false-positive enzyme-linked immunosorbent assay determinations for anti-L-332 IgG among patients with BP is unknown. Conclusion: Anti-L-332 autoantibodies remain a reliable marker for patients with antiepiligrin cicatricial pemphigoid.

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