IgG1 and IgG3 are the Major Immunoglobulin Subclasses Targeting Epitopes within the NC16A Domain of BP180 in Pemphigoid Gestationis

Chimanovitch, Iakov; Schmidt, Enno; Döpp, Rebekka; Bröcker, Eva‐Bettina; Zillikens, Detlef; Messer, Gerald; Partscht, Karin; Giudice, George J.

doi:10.1046/j.1523-1747.1999.00622.x

Cited by 71 publications

(55 citation statements)

References 20 publications

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“…4).20,40 Recent epitope mapping studies identified two well defined antigenic sites within a 22 amino acid segment of BP180 (NC16A2 and NC16A2.5) as the major anti genic targets of PG sera. 41 In contrast to findings in BP,26 reactivity to NC16A is dominated by IgGZ and IgG3 in PG patients. 41 As IgG3 and IgG1 are the IgG subclasses with the strongest complement-fixing prop erties, these observations may well explain complement deposition at the DEJ which is the most consistent immunopathological finding in the skin of PG patients .…”

Section: Pemphigoid Gestationismentioning

confidence: 80%

BP180 as the common autoantigen in blistering diseases with different clinical phenotypes.

Zillikens

2002

Keio j. med

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Abstract. Bullous pemphigoid antigen 180 (BP180, type XVII collagen) is a transmembrane hemi desmosomal glycoprotein of basal keratinocytes that spans the lamina lucida of the dermal-epidermal junction. Five autoimmune subepidermal blistering diseases are associated with an immune response to BP180, including bullous pemphigoid (BP), pemphigoid gestationis (PG), cicatricial pemphigoid (CP), lichen planes pemphigoides (LPP), and linear IgA disease (LAD). The BP180 ectodomain consists of 15 interrupted collagen domains. The largest non-collagenous (NC) 16A domain is located next to the cell membrane. In BP, autoantibodies are directed to a tightly clustered set of epitopes located at the N-terminal 45 amino acids of the NC16A domain. However, some BP sera also react with other por tions of the BP180 ectodomain or with the intracellular region of this protein. In PG, antibodies appear to exclusively recognize the immunodominant BP180 NC16A region. In CP, autoantibodies are directed to both the NC16A domain and the C-terminus of BP180 that projects into the lamina lucida/ lamina densa interface of the dermal-epidermal junction. In LPP, autoantibodies react with an epitope located at the C-terminus of NC16A, that is not targeted by BP or PG sera. Finally, the epidermal 97 kDa and the keratinoctye-derived 120 kDa autoantigens of LAD (LABD97 and LAD-1, respectively) have recently been identified as portions of the BP180 ectodomain. These observations demonstrate that different clinical phenotypes are associated with an autoinunune response to the same autoantigen yet the immunoglobulin subclass of the autoantibody and the epitope that is recognized may be dif ferent. Adhesion of basal keratinocytes to the underlying dermis is maintained by various structural proteins of hemidesmosomes, including the 230 kD bullous pem phigoid antigen (BP230), plectin, a6134 integrin, BP180, and laminin 5. Directly or through other proteins these hemidesmosomal components associate with anchor ing fibrils which originate in the lamina densa of the dermal-epidermal junction (DEJ) and extend into the subjacent connective tissue. The major component of anchoring fibrils is type VII collagen.1Mutations for the different components of this anchoring complex as well as formation of autoanti bodies against these structures result in split forma tion at the level of the DEJ. A major component of the dermal-epidermal anchoring complex and a major target of autoantibodies is BP180. BP180 is a member of the collagen protein family and is also referred to as type XVII collagen. It is a transmembrane glycoprotein with a type II orientation, i.e., the N-terminus localizes to the cytoplasm, whereas the C-terminal ectodomain consisting of about 1,000 amino acids projecting into the extracellular space.2.3 Rotary shadowing revealed that BP180 contains an intracellular globular head, an extracellular rigid rod corresponding to the 16th non collagenous (NC) A and the 15th collagenous domain spanning the lamina lucida, and a flexible tail extend ing into t...

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Section: Pemphigoid Gestationismentioning

confidence: 80%

BP180 as the common autoantigen in blistering diseases with different clinical phenotypes.

Zillikens

2002

Keio j. med

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“…3). Within this membraneproximal stretch of 76 amino acids, PG autoantibodies bind to five well-defined epitopes (designated NC16A1, NC16A2, NC16A2.5, NC16A3 and NC16A5) 42,43 (Fig. 4).…”

Section: Immunopathology and Diagnosismentioning

confidence: 99%

“…In contrast, PG sera do not react with epitope NC16A4, which is a major target of autoantibodies in lichen planus pemphigoides 46,47 . Analysis of immunoglobulin subclasses in PG sera demonstrated that antibodies to BP180 NC16A mainly belong to IgG1 and IgG3 isotypes 42 . This is in contrast to findings in bullous pemphigoid, where IgG4 is the major subclass of anti-BP180 NC16A autoantibodies 48 .…”

Section: Immunopathology and Diagnosismentioning

confidence: 99%

Pemphigoid gestationis: new insights into the pathogenesis lead to novel diagnostic tools

Shimanovich

2002

BJOG: An International Journal of Obstetrics and Gynaecology

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“…PG is driven by auto-antibodies directed to the hemidesmosomal adhesion molecule BP180. IgG auto-antibodies directed against the NC16A domain of BP180 can be found in 90% of patients with PG and, in some cases, remain positive after delivery (4)(5)(6)(7)(8). Autoantibodies against a second hemidesmosomal protein, BP230, have been reported in up to 16% of PG sera (9), but the frequency of anti-BP230 auto-antibodies in healthy controls was not determined in this Japanese study.…”

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confidence: 55%

Value of BIOCHIP Technology in the Serological Diagnosis of Pemphigoid Gestationis

Sadik¹,

Pas²,

Bohlmann³

et al. 2017

Acta Derm Venerol

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IgG1 and IgG3 are the Major Immunoglobulin Subclasses Targeting Epitopes within the NC16A Domain of BP180 in Pemphigoid Gestationis

Cited by 71 publications

References 20 publications

BP180 as the common autoantigen in blistering diseases with different clinical phenotypes.

BP180 as the common autoantigen in blistering diseases with different clinical phenotypes.

Pemphigoid gestationis: new insights into the pathogenesis lead to novel diagnostic tools

Value of BIOCHIP Technology in the Serological Diagnosis of Pemphigoid Gestationis

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