Bullous Pemphigoid, BP180 and BP230, IgG Antibodies, Serum
Bullous pemphigoid (BP) BP180 and BP230 enzyme-linked immunosorbent assay are sensitive, objective, and specific tests that should be considered as an initial screening test in the diagnosis of pemphigoid and its variants.
To compare these results with the standard serum test of indirect immunofluorescence utilizing monkey esophagus substrate.
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Bullous pemphigoid (BP) is chronic pruritic blistering disorder found mainly in aged persons, characterized by the development of tense blisters over an erythematous or urticarial base. IgG antibasement membrane zone antibodies are found in the serum of patients, and linear IgG and C3 sediment is found on the basement membrane zone of the lesion. Several well characterized variants exist including localized, mucous membrane predominant and pemphigoid gestationis, also referred to as herpes gestationis.
Target antigens of the autoantibodies in BP patient serum are BP230 and BP180 also called BPAG1 and BPAG2. Molecular weight of these antigens is 230 kD and 180 kD, respectively. BP180 is thought to be the direct target of the autoantibody because of its location along the basement membranes, and the autoantibody against BP230 is thought to be secondarily produced.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
<9.0 U (negative)
> or =9.0 U (positive)
<9.0 U (negative)
> or =9.0 U (positive)
Antibodies to bullous pemphigoid (BP) BP180 and BP230 have been shown to be present in most patients with pemphigoid. Adequate sensitivities and specificity for disease are documented and Mayo’s experience demonstrates a very good correlation between BP180 and BP230 results and the presence of pemphigoid (see Supportive Data). However, in those patients strongly suspected to have pemphigoid, either by clinical findings or by routine biopsy, and in whom the BP180/BP230 assay is negative, follow-up testing by CIFS / Cutaneous Immunofluorescence Antibodies (IgG), Serum is recommended.
Antibody titer correlates with disease activity in many patients. Patients with severe disease can usually be expected to have high titers of antibodies to BP. Titers are expected to decrease with clinical improvement.
For further information, see Cutaneous Immunofluorecence Testing in Special Instructions.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
As with other diagnostic test procedures, the results obtained with bullous pemphigoid (BP) BP180 and BP230 enzyme-linked immunosorbent assay (ELISA) kit serve only as an aid to diagnosis and should not be interpreted as diagnostic in themselves.
Thirty-two classic bullous pemphigoid (BP), 15 mucous membrane pemphigoid, and 7 other pemphigoid variants, diagnosed by direct immunofluorescence, routine histology, and clinical presentation were tested. Controls included 47 patients with other autoimmune blistering disorders and 42 age-matched controls without skin disease. Forty of 54 (74%) patients with BP and variants tested positive for BP180 and/or BP230 autoantibodies. Of these patients, 28 of 32 (88%) with classical BP, 8 of 15 (53%) with mucous membrane predominant (MMP), and 4 of 7 (57%) of other pemphigoid variants, tested positive.
The calculated sensitivities in classical BP were 54% for BP180 alone and 56% for BP230 alone. The sensitivity increased to 88% with both tests combined, which is comparable to that of indirect immunofluorescence (IIF) (88%). In MMP the calculated sensitivities were 47% for BP180 alone, 13% for BP230 alone, and 53% for both combined. This was slightly less than the sensitivity of IIF (67%). Only 5 of 47 (11%) and 2 of 47 (4%) control patients with other autoimmune blistering disorders were positive for BP180 and BP230 autoantibodies respectively. Interestingly, the 2 patient’s positive for BP230 autoantibody had paraneoplastic pemphigus. One of 42 (2%) and 0 normal controls tested positive for BP180 and BP230 respectively.
The calculated specificities for BP180, BP230, and IIF were 93%, 98%, and 92% respectively.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Liu Z, Diaz LA, Troy JL: A passive transfer model of the organ-specific autoimmune disease, bullous pemphigoid, using antibodies generated against the hemidesmosomal antigen, BP180. J Clin Invest 1993;92:2480-2488
2. Matsumura K, Amagai M, Nishikawa T, Hashimoto T: The majority of bullous pemphigoid and herpes gestationes serum samples react with the NC16a domain of the e180-kD bullous pemphigoid antigen. Arch Dematol Res 1996;288:507-509
3. Stanley JR, Hawley-Nelson P, Yuspa SH, et al: Characterization of bullous pemphigoid antigen: a unique basement membrane protein of stratified aqueous epithelia. Cell 1981;24:897-903
4. Hamada T, Nagata Y, Tmita M, et al: Bullous pemphigoid sera react specially with various domains of BP230, most frequently with C-terminal domain, by immunblot analyses using bacterial recombinant proteins covering the entire molecule. Exp Dermatol 2001;10:256-263