Mucous Membrane Pemphigoid Patients Research Articles

A Prospective Study of Upper Aerodigestive Tract Manifestations of Mucous Membrane Pemphigoid

We conducted a prospective study between 1995 and 2002 to investigate nose and throat (NT) manifestations of mucous membrane pemphigoid (MMP). One hundred ten consecutive patients with clinical, histologic, and immunologic criteria of MMP were seen in 2 referral centers for bullous diseases. They were systematically asked about the existence of persistent NT symptoms. Patients who had any were examined with a flexible nasopharyngolaryngoscope by the same otorhinolaryngologist. When possible, NT mucous membrane (MM) biopsies were taken for direct immunofluorescence (IF) assays to determine lesion specificity. Thirty-eight (35%) patients (23 F/15 M; mean age, 58.5 yr) had the following NT symptoms: 35 (92%) nasal, 19 (50%) pharyngeal, and 10 (26%) laryngeal. Five (13%) had acute dyspnea. Thirty-three (87%) of the 38 symptomatic patients had lesions at physical examination: 30 (79%) nasal, 6 (16%) pharyngeal, and 19 (50%) laryngeal. Laryngeal involvement was asymptomatic in 11 patients. Lesions were mainly atrophic rhinitis and oropharyngeal and epiglottal erosions. Nasal valves, choanae, pharynx, and/or larynx were severely scarred in 7 (18%) patients, causing the death of 3. Direct IF showed malpighian epithelium associated with linear immune deposits (IgG, IgA, or C3) along the chorioepithelial junction in all 18 biopsies performed, including those of 4 symptomatic patients without lesions at physical examination. The presence of severe ophthalmologic lesions (p = 0.02) and > or =3 sites involved other than NT (p = 0.02) were predictive of laryngeal involvement. In contrast, laryngeal symptoms, disease duration, HLA DQB1*0301, and smoking were not significantly associated with laryngeal lesions. In conclusion, at least 35% of MMP patients had NT involvement. Atrophic rhinitis was the most frequent lesion. The most severe were the laryngeal lesions that were significantly associated with severe ocular involvement and disseminated disease, and could be fatal. Our results highlight the necessity of a multidisciplinary approach to MMP management to assure early diagnosis of NT involvement, to guide therapeutic choices, and to improve patient survival and functional outcomes.

Periodontal Status in Patients With Gingival Mucous Membrane Pemphigoid

Mucous membrane pemphigoid (MMP) describes an autoimmune disease with a range of variants, including those with oral, ocular, and cutaneous lesions. Persistent oral lesions, lack of effective oral hygiene, and plaque accumulation may increase the risk of long-term periodontal disease. However, to our knowledge, no studies have evaluated the relationship between the presence of gingival MMP and periodontal health. The purpose of this study was to evaluate the possible impact of gingival pemphigoid lesions on the human periodontium. Twenty patients with histologic confirmation of subepithelial separation with or without direct immunofluorescence testing were randomly chosen to participate in a study evaluating their periodontal status. Parameters evaluated included plaque score, gingival index, bleeding index, probing depths, recession, clinical attachment level, mobility, furcation involvement, number of missing teeth, and Machtei criteria, a previously defined criteria for periodontitis. Individuals matched with respect to age, gender, and smoking history were selected and evaluated for the same parameters. MMP patients had statistically significant larger mean gingival index scores than age, gender, and smoking history matched controls. Plaque scores, bleeding index, mobility, furcations, clinical attachment level, recession, and periodontal status did not show statistically significant differences between MMP and control patients. A statistically significant difference in plaque index was found when patients with MMP in treatment were compared to patients with MMP in remission. Among patients with MMP, those diagnosed >5 years in the past had statistically significantly greater Class I furcation involvement and recession on facial and lingual surfaces of teeth. A relationship was found to suggest that patients with MMP exhibit more gingival inflammation than a control population. Among patients with MMP, patients currently in treatment have higher plaque indices than those in remission and not receiving treatment. Furthermore, when comparing patients with MMP who received a diagnosis>5 years in the past to those with a diagnosis in the past 5 years, statistically significantly greater Class I furcation and facial and lingual recession were measured. Long-term follow-up in this population may provide additional information as to periodontal progression in MMP versus control patients.

Bullous pemphigoid antigen II (BP180) and its soluble extracellular domains are major autoantigens in mucous membrane pemphigoid: the pathogenic relevance to HLA class II alleles and disease severity

Mucous membrane pemphigoid (MMP), a chronic autoimmune subepithelial blistering disease, is associated with circulating IgG and/or IgA autoantibodies against several basement membrane zone antigens. The heterogeneity of clinical presentation and diversity of target autoantigens have contributed to difficulties in characterizing this condition immunologically. To analyse serum autoantibody profile and HLA class II alleles in MMP patients and to correlate this with the clinical presentation of disease. Well-defined subgroups consisting of 124 patients with MMP were examined for IgG and IgA reactivity with immunoblotting using human epidermal, dermal and placental amnion proteins. The results were further analysed on the basis of detailed clinical (sites of involvement and disease severity) and immunopathological criteria (immunofluorescence study and HLA class II alleles). Immunoblot assay revealed that the majority of MMP patients had IgG (93 of 124, 75%) and/or IgA autoantibodies (63 of 124, 51%) to BP180 (including its soluble ectodomains, 120-kDa LAD-1 and 97-kDa LABD97 antigens). Other antigens targeted predominantly by IgG autoantibodies included: BP230 in 34 (27%), beta4 integrin in 26 (21%), and laminin 5 in three (2%). All the BP230+ sera and 23 (88%) beta4 integrin+ sera also reacted with at least one of the BP180 antigens. Over 85% of patients with reactivity to beta4 integrin had ocular involvement. In most cases of MMP, more severe clinical features were associated with antibody reactivity to multiple basement membrane zone antigens, as well as reactivity to multiple BP180 component antigens. Dual BP180/LAD-1 reactivity with IgG and IgA was associated with a more severe phenotype. In addition, the subset-dependent autoantibody reactivity correlated well with specific HLA class II alleles, DQB1*0301, DRB1*04 and DRB1*11. Our results confirmed that BP180 is a major autoantigen targeted by the sera of patients with MMP. The disease-prevalent HLA class II alleles and humoral autoimmune response against the particular subsets of antigenic epitope(s) within BP180 ectodomain may contribute to the clinicopathological significance and disease severity of MMP.

Detection of Laminin 5-Specific Auto-antibodies in Mucous Membrane and Bullous Pemphigoid Sera by ELISA

Mucous membrane pemphigoid (MMP) is an autoimmune bullous disease that primarily affects mucous membranes leading to a scarring phenotype. MMP patients produce auto-antibodies (auto-ab) that preferentially recognize two components of the dermoepidermal basement membrane zone (BMZ): bullous pemphigoid (BP)180 and laminin 5 (LN5). Since detection of disease-specific auto-ab may be critical for diagnosis of MMP, we developed an ELISA with affinity-purified native human LN5. A total of 24 MMP, 72 BP, and 51 control sera were analyzed for LN5-specific auto-ab: 18/24 (75.0%) MMP and 29/72 (40.3%) BP sera were LN5 reactive. Sensitivity and specificity of the LN5 ELISA for MMP were 75% and 84.3%, respectively, and 40.3% and 88.2% for BP, respectively. The LN5 ELISA was more sensitive than a dot blot assay with native LN5, which detected LN5-reactive IgG in 14/24 (58.3%) MMP and 16/72 (22.2%) BP sera. In MMP, but not BP, levels of LN5-reactive IgG correlated with disease severity. Furthermore, IgG reactivity to LN5 of the MMP and BP sera was not significantly associated with IgG reactivity against other autoantigens of the BMZ, such as BP180 or BP230. Thus, the established LN5 ELISA holds great promise as a novel diagnostic and prognostic parameter for MMP.

HLA-DQB1 alleles in Italian patients with mucous membrane pemphigoid predominantly affecting the oral cavity.

Mucous membrane pemphigoid (MMP) used to be considered as a single entity but it is now evident that a range of variants exists. Among them, pure ocular cicatricial pemphigoid (OCP) and pure oral pemphigoid (OP) appear to be very different subsets. Previous immunogenetics studies have found increased occurrence of the DQB1*0301 allele mainly in patients with OCP whereas in patients with OP the data are more open to doubt. To analyse HLA predisposition in a group of Italian patients with MMP predominantly affecting the oral cavity. We carried out high-resolution typing of HLA-DQB1 alleles in 28 patients with MMP predominantly affecting the oral cavity and in 97 geographically matched, healthy controls. All were Italian caucasians. The frequency of HLA-DQB1*0301 was significantly increased in the MMP patients compared with the controls (96% vs. 48%; corrected P, Pc = 0.001; relative risk, RR = 28.73). A strong association with DQB1*0301 was also evident in patients with OP compared with the controls (95% vs. 48%; Pc = 0.01; RR = 20.21). There was no significant difference in DQB1*0301 frequency between patients with OP and with MMP not restricted to the oral cavity. Patients with MMP were more frequently homozygous for DQB1*0301 than the controls (43% vs. 8%; Pc < 0.001; RR = 8.34). Our data suggest that Italian patients with MMP lesions predominantly affecting the oral cavity present the same genetic predisposition linked to HLA-DQB1*0301 previously reported mainly in patients with OCP.

The Immunoglobulin A Antibody Response in Clinical Subsets of Mucous Membrane Pemphigoid

Background: Mucous membrane pemphigoid (MMP) is an immunobullous disease. In MMP there is frequently a mixed antibody response with the presence of IgA and/or IgG antibodies directed toward basement membrane zone antigens. The IgG antibody response in MMP has been studied, but the antigens to which the IgA antibodies react have not been studied. Objective: To determine the IgA autoantibody reactivity profiles in patients with MMP. Methods: Patients who had both ocular and oral MMP were compared with patients who had ocular or oral MMP and with patients who had cutaneous linear IgA disease (LABD) by Western immunoblot studies. Results: Five of 15 MMP patients and 1 of 5 LABD patients had IgA antibodies reactive with the 180-kD bullous pemphigoid antigen. Seven of 15 MMP patients had IgA antibodies reactive with the 97-kD LABD antigen. Conclusion: Major antigens in IgA MMP are the 180-kD bullous pemphigoid antigen and the 97-kD LABD antigen.