Combination of Various Serological Tests Improves Diagnosis of Oral Mucous Membrane Pemphigoid

Various autoimmune bullous diseases (ABDs) frequently involve oral cavity. ABDs show autoantibodies to various epithelial adhesion molecules or extracellular matrices. Mucous membrane pemphigoid (MMP) is one rare type of ABDs, which predominantly involves mucous membranes and shows various autoantibodies¹. MMP most commonly affects oral mucosa, followed by ocular, nasal, genital, pharyngeal, esophageal, laryngeal and anal mucosae.

   On immunofluorescence, MMP is known to show IgG and/or IgA antibodies against epithelial basement membrane zone. MMP sera react with a number of different BMZ antigens. Among them, approximately 70% of MMP patients show IgG and/or IgA antibodies against BP180 C-terminal domain, and are diagnosed as anti-BP180-type MMP. In addition, approximately 20% of MMP patients show IgG antibodies against various subunits of laminin-332, and are diagnosed as anti-laminin-332-type MMP. Anti-BP180-type and anti-laminin-332-type MMP sera react with the epidermal and dermal sides on indirect immunofluorescence of 1 M NaCl-split skin, respectively.

   Thus, MMP is very heterogeneous, which leads to difficulty in its diagnosis. The variable clinical and histopathological features lead to frequent misdiagnosis of MMP patients. The patients tend to be diagnosed as other acute or chronic inflammatory conditions.

   In this study, to improve the present diagnosis strategy of MMP, three types of different immunological methods (indirect immunofluorescence, various immunoblotting analyses and ELISAs) were employed to analyze the circulating antibodies in 30 patients with oral mucosal lesions, who suspected MMP. The patients were most commonly affected the gingiva (70%) and buccal mucosa (60%), and 10 patients showed only gingival lesions. Less commonly affected sites were the palate (27%), tongue (13%) and lip (13%). Two patients had pharyngeal and/or laryngeal lesions, and three patients had skin lesions. No ocular mucosal involvement was seen. From the results of various serological tests, seventeen, four and three patients were diagnosed as anti-BP180-type MMP, anti-laminin-332-type MMP and concurrence of both types, respectively. The diagnosis of anti-BP180-type MMP was mainly made by immunofluorescence and/or immunoblotting, while the diagnosis of anti-laminin-332-type MMP was mainly made by immunoblotting. Interestingly, the current ELISA of BP180 NC16a domain RP was able to make diagnosis in half of anti-BP180-type MMP patients. We statistically analyzed the clinical features among different MMP groups using Student’s t-test and Pearson’s chi-squared test. Statistical analysis revealed that IgA antibodies had significantly higher reactivity with BP180 C-terminal domain than NC16a domain (P<0.01).

   In conclusion, our results suggested that a combination of multiple immunological tests for circulating autoantibodies is useful for diagnosis of MMP and contributes to a better clinical prognosis in ABD patients.²

1                Schmidt E, Zillikens D. Pemphigoid diseases. Lancet 2013; 381: 320-32.

2                Hayakawa T, Furumura M, Fukano H et al. Diagnosis of oral mucous membrane pemphigoid by means of combined serologic testing. Oral Surg Oral Med Oral Pathol Oral Radiol 2013.