Prospective study in bullous pemphigoid: association of high serum anti-BP180 IgG levels with increased mortality and reduced Karnofsky score

Holtsche, Maike M.; Goletz, Stephanie; Beek, Nina van; Zillikens, Detlef; Benoit, Sandrine; Harman, K. E.; Walton, Shernaz; English, J.S.C.; Sticherling, Michael; Chapman, Anna; Levell, N. J.; Groves, Richard; Williams, Hywel C; König, Inke R.; Schmidt, Enno

doi:10.1111/bjd.16553

Cited by 31 publications

(26 citation statements)

References 43 publications

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“…Risk factors related to increased mortality in BP include older age, neurological disorder (dementia, including Alzheimer's disease and other types of dementia, and stroke), and increased serum levels of anti-BP180 NC16A IgG. 71 , 72…”

Section: Prognosismentioning

confidence: 99%

Bullous pemphigoid

Miyamoto

Santi

Aoki

et al. 2019

An. Bras. Dermatol.

142

159

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Bullous pemphigoid is the most frequent autoimmune bullous disease and mainly affects elderly individuals. Increase in incidence rates in the past decades has been attributed to population aging, drug-induced cases and improvement in the diagnosis of the nonbullous presentations of the disease. A dysregulated T cell immune response and synthesis of IgG and IgE autoantibodies against hemidesmosomal proteins (BP180 and BP230) lead to neutrophil chemotaxis and degradation of the basement membrane zone. Bullous pemphigoid classically manifests with tense blisters over urticarial plaques on the trunk and extremities accompanied by intense pruritus. Mucosal involvement is rarely reported. Diagnosis relies on (1) the histopathological evaluation demonstrating eosinophilic spongiosis or a subepidermal detachment with eosinophils; (2) the detection of IgG and/or C3 deposition at the basement membrane zone using direct or indirect immunofluorescence assays; and (3) quantification of circulating autoantibodies against BP180 and/or BP230 using ELISA. Bullous pemphigoid is often associated with multiple comorbidities in elderly individuals, especially neurological disorders and increased thrombotic risk, reaching a 1-year mortality rate of 23%. Treatment has to be tailored according to the patient's clinical conditions and disease severity. High potency topical steroids and systemic steroids are the current mainstay of therapy. Recent randomized controlled studies have demonstrated the benefit and safety of adjuvant treatment with doxycycline, dapsone and immunosuppressants aiming a reduction in the cumulative steroid dose and mortality.

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Section: Prognosismentioning

confidence: 99%

Bullous pemphigoid

Miyamoto

Santi

Aoki

et al. 2019

An. Bras. Dermatol.

142

159

View full text Add to dashboard Cite

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“…The IgG directed against BP180 domains other than NC16A seemed to be responsible of less inflammatory manifestations (28) due to the fact that they hardly induce any BP180 depletion respect to anti-BP180-NC16A IgG in experimental studies (29). Moreover, IgG reactivity with extracellular but not intracellular epitopes of BP180 paralleled the severity of the disease course (25) and higher levels of anti-BP180 IgG were associated with increased 1-year mortality (30). The pathogenic role of IgG anti-BP180 has been validated by the following remarks: (i) the induction of BP-like lesions in mice in which anti-BP180-NC16A antibodies had been passively transferred (31); (ii) the onset of BP-like bullae and a human disease phenotype in BP180-knockout mice rescued by the human ortholog after being injected with IgG from BP patients (32); (iii) the direct correlation of anti-BP180-NC16A antibody titers to disease activity (33, 34).…”

Section: Established Status Of Knowledge On Bullous Pemphigoid Pathogmentioning

confidence: 99%

New Insights Into the Pathogenesis of Bullous Pemphigoid: 2019 Update

et al. 2019

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There are several lines of evidence indicating that the physiopathological bases of bullous pemphigoid (BP), the most common subepidermal autoimmune bullous disease, are hallmarked by the production of autoantibodies directed against the hemidesmosomal anchoring proteins BP180 and BP230. In contrast to the robustness of the latter assumption, the multifaceted complexity of upstream and downstream mechanisms implied in the pathogenesis of BP remains an area of intense speculation. So far, an imbalance between T regulatory cells and autoreactive T helper (Th) cells has been regarded as the main pathogenic factor triggering the autoimmune response in BP patients. However, the contributory role of signaling pathways fostering the B cell stimulation, such as Toll-like receptor activation, as well as that of ancillary inflammatory mechanisms responsible for blister formation, such as Th17 axis stimulation and the activation of the coagulation cascade, are still a matter of debate. In the same way, the pathomechanisms implied in the loss of dermal-epidermal adhesion secondary to autoantibodies binding are not fully understood. Herein, we review in detail the current concepts and controversies on the complex pathogenesis of BP, shedding light on the most recent theories emerging from the literature.

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“…Second, the diagnosis of BP, like in the BLISTER study (55) was based on clinical presentation and DIF. Subsequent serological analysis of the BLISTER Study confirmed BP diagnosis in almost 90% of the cases (56). Hence, a maximum of 10% of our patient population may have had an alternative diagnosis, such as p200 pemphigoid, mucous membrane pemphigoid or epidermolysis bullosa acquisita.…”

Section: Discussionmentioning

confidence: 91%

Proinflammatory Cytokine Gene Polymorphisms in Bullous Pemphigoid

et al. 2019

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Bullous pemphigoid (BP) is a rare autoimmune skin blistering disease, characterized by the presence of autoantibodies against hemidesmosomal autoantigens. Cytokine expression is altered in BP patients, and several of these differently expressed cytokines, including IL-1α, IL-1β, IL-8, and TNF-α, contribute to disease pathogenesis. Since genetic polymorphisms in the genes of these cytokines might be implicated in susceptibility to BP disease, we aimed at testing this implication in susceptibility to BP in an Iranian cohort. Blood samples were collected from the subjects and genomic DNA was extracted. To detect the single nucleotide polymorphisms (SNPs), IL-1 α (rs1800587), IL-1 β (rs1143627, rs16944, rs1143634), IL-8 (rs4073), and TNF- α (rs1799964, rs1800630, rs1799724, and rs361525) genes were genotyped in BP patients and healthy controls as well as IL-8 (rs4073) in pemphigus vulgaris (PV) patients. Quantitative gene expression was evaluated by RT-PCR analysis. A significant difference was observed in the distribution of genotypes or alleles of IL-8 SNP between the BP patients and controls. The A-allele of IL-8 SNP is significantly more prevalent in the control individuals compared to the BP patient. To further validate this observation, we included PV patients as an additional control. Again, the A-allele of IL-8 SNP is significantly more prevalent in the PV compared to the BP patients. While we observed a trend toward significant differences regarding alleles of TNF- α rs1799724 as well as alleles of TNF- α rs1799964, this difference was, however, not evident after correction for multiple analysis. There was no significant difference in all other studied SNPs. In contrast to IL-1 α, IL-1 β, and TNF- α, IL-8 gene expression levels were significantly higher in the patients than that of controls. The minor allele in IL-8 SNP might play a protective role in susceptibility to BP in Iranian patients. Although higher expression levels of IL-8 gene was found in the patients compared with healthy controls, these levels, however, suggest no association with the examined polymorphism. Moreover, further investigation revealed an elevation in gene expression between wild and polymorphic genotypes of IL-1 α rs1800587 and TNF- α rs361525 in the patient group and these SNPs are therefore associated with altering the levels of gene expression.

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Prospective study in bullous pemphigoid: association of high serum anti-BP180 IgG levels with increased mortality and reduced Karnofsky score

Abstract: Analysis of the autoantibody profile is not only of diagnostic relevance but may also be helpful in predicting the course of the disease.

Cited by 31 publications

References 43 publications

Bullous pemphigoid

Bullous pemphigoid

New Insights Into the Pathogenesis of Bullous Pemphigoid: 2019 Update

Proinflammatory Cytokine Gene Polymorphisms in Bullous Pemphigoid

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