Non-Cochrane · DTA · PM41387261
Diagnostic Agreement in Subepidermal Blistering Diseases: Is ELISA Test Reliable as Direct Immunofluorescence? A Systematic Review, Meta-Analysis, and Trial Sequential Analysis.
Patini Romeo, Gioco Gioele, Mignogna Michele Davide, et al. · Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology · 2026 · PubMed · doi:10.1111/jop.70088
Findings
5 findings
| Population | ||||
|---|---|---|---|---|
| DIF-confirmed patients with subepidermal blistering diseases (BP, PG, MMP, EBA, anti-p200 pemphigoid, LABD, dermatitis herpetiformis) tested before immunosuppressive therapy | ELISA for BP180 autoantibodies (index test) | Direct immunofluorescence (DIF, reference standard) | Diagnostic agreement between ELISA and DIF (risk difference in test positivity) At first diagnosis, before immunosuppressive therapy · Hospital dermatology and oral medicine settings, mostly Europe | RD 0.26 [0.19, 0.33] GRADE not reported Downgraded: risk of bias, imprecision, inconsistency 35 studies · 2776 participants |
| DIF-confirmed patients with subepidermal blistering diseases (BP, PG, MMP, EBA, anti-p200 pemphigoid, LABD, dermatitis herpetiformis) tested before immunosuppressive therapy | ELISA for BP230 autoantibodies (index test) | Direct immunofluorescence (DIF, reference standard) | Diagnostic agreement between ELISA and DIF (risk difference in test positivity) At first diagnosis, before immunosuppressive therapy · Hospital dermatology and oral medicine settings, mostly Europe | RD 0.59 [0.47, 0.71] GRADE not reported Downgraded: risk of bias, imprecision, inconsistency 27 studies · 2097 participants |
| DIF-confirmed patients with subepidermal blistering diseases (BP, PG, MMP, EBA, anti-p200 pemphigoid, LABD, dermatitis herpetiformis) tested before immunosuppressive therapy | ELISA for Lam332 autoantibodies (index test) | Direct immunofluorescence (DIF, reference standard) | Diagnostic agreement between ELISA and DIF (risk difference in test positivity) At first diagnosis, before immunosuppressive therapy · Hospital dermatology and oral medicine settings, mostly Europe | RD 0.82 [0.7, 0.94] GRADE not reported Downgraded: risk of bias, imprecision, inconsistency 4 studies · 365 participants |
| DIF-confirmed patients with bullous pemphigoid (BP) | ELISA (BP180 and/or BP230) in bullous pemphigoid (index test) | Direct immunofluorescence (DIF, reference standard) | Diagnostic agreement between ELISA and DIF (risk difference in test positivity) At first diagnosis, before immunosuppressive therapy · Hospital dermatology and oral medicine settings, mostly Europe | RD 0.19 [0.13, 0.25] GRADE not reported Downgraded: risk of bias, imprecision, inconsistency 27 studies · 2238 participants |
| DIF-confirmed patients with mucous membrane pemphigoid (MMP) | ELISA (BP180, BP230 and/or Lam332) in mucous membrane pemphigoid (index test) | Direct immunofluorescence (DIF, reference standard) | Diagnostic agreement between ELISA and DIF (risk difference in test positivity) At first diagnosis, before immunosuppressive therapy · Hospital dermatology and oral medicine settings, mostly Europe | RD 0.55 [0.43, 0.67] GRADE not reported Downgraded: risk of bias, imprecision, inconsistency 7 studies · 489 participants |
Included primary studies 38
Open in Studies| Study | Year | Also included by | Outcomes it informs here | Trial data |
|---|---|---|---|---|
| Barnadas 2008 Enzyme-linked immunosorbent assay (ELISA) and indirect immunofluorescence testing in a bullous pemphigoid and pemphigoid gestationis. PMID:19126009 | 2008 | this review only | Diagnostic agreement between ELISA and DIF (risk difference in test positivity) | not extracted yet |
| Bernard 2013 Prevalence and clinical significance of anti-laminin 332 autoantibodies detected by a novel enzyme-linked immunosorbent assay in mucous… PMID:23426192 | 2013 | this review only | Diagnostic agreement between ELISA and DIF (risk difference in test positivity) | not extracted yet |
| Bing 2015 Levels of anti-BP180 NC16A IgE do not correlate with severity of disease in the early stages of bullous pemphigoid. PMID:26404084 | 2015 | this review only | Diagnostic agreement between ELISA and DIF (risk difference in test positivity) | not extracted yet |
| Chanprapaph 2021 Anti-BP180 and anti-BP230 enzyme-linked immunosorbent assays for diagnosis and disease activity tracking of bullous pemphigoid: A… PMID:31175713 | 2021 | this review only | Diagnostic agreement between ELISA and DIF (risk difference in test positivity) | not extracted yet |
| Charneux 2011 Usefulness of BP230 and BP180-NC16a enzyme-linked immunosorbent assays in the initial diagnosis of bullous pemphigoid: a retrospective… PMID:21422334 | 2011 | this review only | Diagnostic agreement between ELISA and DIF (risk difference in test positivity) | not extracted yet |
| Cozzani 2016 Autoantibody Profile of a Cohort of 78 Italian Patients with Mucous Membrane Pemphigoid: Correlation Between Reactivity Profile and… PMID:26631393 | 2016 | this review only | Diagnostic agreement between ELISA and DIF (risk difference in test positivity) | not extracted yet |
| Cozzani 2020 Autoantibody Profile of a Cohort of 54 Italian Patients with Linear IgA Bullous Dermatosis: LAD-1 Denoted as a Major Auto-antigen of the… PMID:32011724 | 2020 | this review only | Diagnostic agreement between ELISA and DIF (risk difference in test positivity) | not extracted yet |
| Dart 2021 Autoantibody Detection for Diagnosis in Direct Immunofluorescence-Negative Mucous Membrane Pemphigoid: Ocular and Other Sites Compared. PMID:32745569 | 2021 | this review only | Diagnostic agreement between ELISA and DIF (risk difference in test positivity) | not extracted yet |
| Dikmen 2022 Serum autoantibody reactivity in bullous pemphigoid is associated with neuropsychiatric disorders and the use of antidiabetics and… PMID:35796163 | 2022 | this review only | Diagnostic agreement between ELISA and DIF (risk difference in test positivity) | not extracted yet |
| Esmaili 2015 Diagnostic accuracy of BP180 NC16a and BP230-C3 ELISA in serum and saliva of patients with bullous pemphigoid. PMID:25476471 | 2015 | this review only | Diagnostic agreement between ELISA and DIF (risk difference in test positivity) | not extracted yet |
| Fania 2012 IgE recognition of bullous pemphigoid (BP)180 and BP230 in BP patients and elderly individuals with pruritic dermatoses. PMID:22534318 | 2012 | this review only | Diagnostic agreement between ELISA and DIF (risk difference in test positivity) | not extracted yet |
| Feliciani 2009 IgG autoantibody reactivity against bullous pemphigoid (BP) 180 and BP230 in elderly patients with pruritic dermatoses. PMID:19485996 | 2009 | this review only | Diagnostic agreement between ELISA and DIF (risk difference in test positivity) | not extracted yet |
| Gasparini 2022 Anti-laminin 332 antibody detection using biochip immunofluorescence microscopy in a real-life cohort of Italian patients with mucous… PMID:36856373 | 2022 | this review only | Diagnostic agreement between ELISA and DIF (risk difference in test positivity) | not extracted yet |
| Giusti 2018 Anti-Type VII Collagen Antibodies Are Identified in a Subpopulation of Bullous Pemphigoid Patients With Relapse. PMID:29619029 | 2018 | this review only | Diagnostic agreement between ELISA and DIF (risk difference in test positivity) | not extracted yet |
| Gornowicz-Porowska 2017a Analysis of the autoimmune response against BP180 and BP230 in ethnic Poles with neurodegenerative disorders and bullous pemphigoid. PMID:28680335 | 2017 | this review only | Diagnostic agreement between ELISA and DIF (risk difference in test positivity) | not extracted yet |
| Gornowicz-Porowska 2017b Accuracy of molecular diagnostics in pemphigus and bullous pemphigoid: comparison of commercial and modified mosaic indirect… PMID:28261028 | 2017 | this review only | Diagnostic agreement between ELISA and DIF (risk difference in test positivity) | not extracted yet |
| Gornowicz-Porowska 2022 A Probing of the Issue of Detecting IgG, IgG4 and IgA Antibodies to Laminin 332 Epitopes in Mucous Membrane Pemphigoid: A… PMID:35510222 | 2022 | this review only | Diagnostic agreement between ELISA and DIF (risk difference in test positivity) | not extracted yet |
| Grootenboer-Mignot 2010 Place of human amniotic membrane immunoblotting in the diagnosis of autoimmune bullous dermatoses. PMID:19886889 | 2010 | this review only | Diagnostic agreement between ELISA and DIF (risk difference in test positivity) | not extracted yet |
| Groth 2011 Development of a simple enzyme-linked immunosorbent assay for the detection of autoantibodies in anti-p200 pemphigoid. PMID:20854435 | 2011 | this review only | not stated | not extracted yet |
| Hofmann 2002 Severity and phenotype of bullous pemphigoid relate to autoantibody profile against the NH2- and COOH-terminal regions of the BP180… PMID:12445194 | 2002 | this review only | Diagnostic agreement between ELISA and DIF (risk difference in test positivity) | not extracted yet |
| Keller 2016 Evaluation of ELISA testing for BP180 and BP230 as a diagnostic modality for bullous pemphigoid: a clinical experience. PMID:26895534 | 2016 | this review only | Diagnostic agreement between ELISA and DIF (risk difference in test positivity) | not extracted yet |
| Kromminga 2004 Development of an ELISA for the detection of autoantibodies to BP230. PMID:15093564 | 2004 | this review only | Diagnostic agreement between ELISA and DIF (risk difference in test positivity) | not extracted yet |
| Lee 2012 Usefulness of Enzyme-linked Immunosorbent Assay Using Recombinant BP180 and BP230 for Serodiagnosis and Monitoring Disease Activity of… PMID:22363155 | 2012 | this review only | Diagnostic agreement between ELISA and DIF (risk difference in test positivity) | not extracted yet |
| Li 2022 Diagnostic values of indirect immunofluorescence using salt-split skin, direct immunofluorescence and BP180 NC16A ELISA on bullous… PMID:35830249 | 2022 | this review only | Diagnostic agreement between ELISA and DIF (risk difference in test positivity) | not extracted yet |
| Mariotti 2004 Development of a novel ELISA system for detection of anti-BP180 IgG and characterization of autoantibody profile in bullous pemphigoid… PMID:15541078 | 2004 | this review only | Diagnostic agreement between ELISA and DIF (risk difference in test positivity) | not extracted yet |
| Messingham 2009 A novel ELISA reveals high frequencies of BP180-specific IgE production in bullous pemphigoid. PMID:19422829 | 2009 | this review only | Diagnostic agreement between ELISA and DIF (risk difference in test positivity) | not extracted yet |
| Patsatsi 2008 Detection of anti-BP180NC16a and anti-BP230 autoantibodies in blister fluid of patients with bullous pemphigoid: the first survey in Greece. PMID:18093242 | 2008 | this review only | Diagnostic agreement between ELISA and DIF (risk difference in test positivity) | not extracted yet |
| Petruzzi 2021 Evaluation of BP180-NC16A ELISA in exclusive oral pemphigoid diagnosis. A comparative study. PMID:32726466 | 2021 | this review only | Diagnostic agreement between ELISA and DIF (risk difference in test positivity) | not extracted yet |
| Sakuma-Oyama 2004 Evaluation of a BP180-NC16a enzyme-linked immunosorbent assay in the initial diagnosis of bullous pemphigoid. PMID:15270881 | 2004 | this review only | Diagnostic agreement between ELISA and DIF (risk difference in test positivity) | not extracted yet |
| Sernicola 2019 Biochip detection of BP180 autoantibodies in blister fluid for the serodiagnosis of bullous pemphigoid: A pilot study. PMID:30762788 | 2019 | this review only | Diagnostic agreement between ELISA and DIF (risk difference in test positivity) | not extracted yet |
| Sitaru 2007 Enzyme-linked immunosorbent assay using multimers of the 16th non-collagenous domain of the BP180 antigen for sensitive and specific… PMID:17697150 | 2007 | this review only | Diagnostic agreement between ELISA and DIF (risk difference in test positivity) | not extracted yet |
| Tampoia 2009 Evaluation of a new ELISA assay for detection of BP230 autoantibodies in bullous pemphigoid. PMID:19758126 | 2009 | this review only | Diagnostic agreement between ELISA and DIF (risk difference in test positivity) | not extracted yet |
| Tani 2015 Clinical and immunological profiles of 25 patients with pemphigoid gestationis. PMID:25154546 | 2015 | this review only | Diagnostic agreement between ELISA and DIF (risk difference in test positivity) | not extracted yet |
| Terra 2011 Immunofluorescence serration pattern analysis as a diagnostic criterion in antilaminin-332 mucous membrane pemphigoid: immunopathological… PMID:21692774 | 2011 | this review only | Diagnostic agreement between ELISA and DIF (risk difference in test positivity) | not extracted yet |
| Treco 2023 Elevated levels of sCD48 are inversely correlated with markers of disease activity in bullous pemphigoid. PMID:36134505 | 2023 | this review only | Diagnostic agreement between ELISA and DIF (risk difference in test positivity) | not extracted yet |
| Van Beek 2022 Evaluation of Site- and Autoantigen-Specific Characteristics of Mucous Membrane Pemphigoid. PMID:34817539 | 2022 | this review only | Diagnostic agreement between ELISA and DIF (risk difference in test positivity) | not extracted yet |
| Yang 2012 Evaluation of the combination of BP180-NC16a enzyme-linked immunosorbent assay and BP230 enzyme-linked immunosorbent assay in the… PMID:23075641 | 2012 | this review only | Diagnostic agreement between ELISA and DIF (risk difference in test positivity) | not extracted yet |
| Zillikens 1997 A highly sensitive enzyme-linked immunosorbent assay for the detection of circulating anti-BP180 autoantibodies in patients with bullous… PMID:9347799 | 1997 | this review only | Diagnostic agreement between ELISA and DIF (risk difference in test positivity) | not extracted yet |
Review question
| Element | Planned (methods) | Found (results) |
|---|---|---|
| Population | Patients with subepidermal blistering diseases (BP, PG, MMP, EBA, anti-p200 pemphigoid, LABD, dermatitis herpetiformis) diagnosed by clinical, histopathology and DIF | Patients with BP (27 studies, n=2238 in MA), MMP (7 studies, n=489), LABD, anti-p200 pemphigoid, PG, pruritic dermatoses (n=38 studies) |
| Intervention | ELISA (BP180, BP230, Lam332, integrin a6b4, COL7, LAM-g1, LAD-1, transglutaminase) | ELISA against BP180 (35 studies), BP230 (27), Lam332 (4), COL7 (1), LAM-g1 (1) |
| Comparison | Direct immunofluorescence (DIF) | DIF (positive in all included patients) |
| Outcomes | Diagnostic agreement (risk difference in diagnostic yield) | Risk difference in positivity DIF vs ELISA: BP 0.19; MMP 0.55; BP180 0.26; BP230 0.59; Lam332 0.82 |
| Study designs | Cohort and case-control studies | 24 prospective and 14 retrospective cohort or case-control studies (n=38) |
| Timing | ELISA at first diagnosis, before immunosuppressive therapy | At diagnosis before immunosuppressive therapy; studies 1997 to 2022 |