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Autoantibody detection for diagnosis in direct immunofluorescence negative mucous membrane pemphigoid: ocular and other sites compared

Research output: Contribution to journalArticle

John Dart, Jane Setterfield, Richard W. Groves, John B. Mee, Gilles F.h. Diercks, Hendri H. Pas, Darwin Minassian

Original languageEnglish
JournalOphthalmology
Early online date30 Jul 2020
DOIs
Publication statusE-pub ahead of print - 30 Jul 2020

King's Authors

Abstract

Objective
To assess whether a panel of serum pemphigoid autoantibody tests could be used to confirm an immunopathological diagnosis of mucous membrane pemphigoid (MMP) in direct immunofluorescent negative (DIF-) MMP patients.
Design
Prospective cross-sectional study.
Subjects and controls
76 patients with MMP involving ocular and non-ocular sites with 45 matched controls.
Tests
Enzyme linked immunosorbent assays (ELISA) for BP180 and BP230 (MBL International®), IgA and IgG indirect immunofluorescence on human salt-split skin (IIF SSS) and the keratinocyte footprint assay for anti-laminin 332 antibodies.
Main outcome measures
Sensitivity and specificity of autoantibody detection; significant differences for individual tests and test combinations for MMP involving different sites.
Results
All DIF- Cases (24/76, 31.8%) had either ocular only disease or ocular involvement in multi-site disease. Serum pemphigoid autoantibodies were detected in 29/76 (38.2%) of all MMP patients compared to 3/45 (6.7%) of controls. Autoantibody reactivity detected by any one or more of the tests was present in 6/24 (25%) DIF- cases compared to 22/49 (44.9%) in DIF positive (DIF+). Compared to controls ocular only MMP serum reactivity was not significantly different for any test or test combination whereas DIF- multisite ocular MMP differed for one ELISA and 3/7 test combinations. By contrast, for DIF+ non ocular MMP all the individual tests, apart from IgA IIF, and all test combinations were significantly different compared to controls. For the whole MMP cohort the sensitivity of all tests was low having a maximum of 21.05% for BP180 reactivity, increasing to 38.16% for an optimal test combination. Disease activity was strongly associated with positive serology findings.
Conclusions
Pemphigoid serum autoantibody tests did not provide alternative immunopathological evidence of MMP in ocular only MMP patients but had limited value in DIF- multisite ocular MMP. The requirement for immunopathological confirmation of MMP by autoantibody detection is inappropriate for DIF- ocular only MMP resulting in missed diagnoses, delayed therapy and poor outcomes. Alternative diagnostic criteria for MMP with ocular involvement are required, to exclude the other causes of scarring conjunctivitis, until more sensitive and specific immunopathology tests become available.

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