The relevance of complement in pemphigoid diseases: A critical appraisal

Pemphigoid diseases are autoimmune chronic inflammatory skin diseases, which are characterized by blistering of the skin and/or mucous membranes, and circulating and tissue-bound autoantibodies. The well-established pathomechanisms comprise autoantibodies targeting various structural proteins located at the dermal-epidermal junction, leading to complement factor binding and activation. Several effector cells are thus attracted and activated, which in turn inflict characteristic tissue damage and subepidermal blistering. Moreover, the detection of linear complement deposits in the skin is a diagnostic hallmark of all pemphigoid diseases. However, recent studies showed that blistering might also occur independently of complement. This review reassesses the importance of complement in pemphigoid diseases based on current research by contrasting and contextualizing data from in vitro, murine and human studies

Complement-Activating Capacity of Autoantibodies Correlates With Disease Activity in Bullous Pemphigoid Patients

Background: Bullous pemphigoid is a subepidermal blistering skin disease, associated with autoantibodies to hemidesmosomal proteins, complement activation at the dermal-epidermal junction, and dermal granulocyte infiltration. Clinical and experimental laboratory findings support conflicting hypotheses regarding the role of complement activation for the skin blistering induced by pemphigoid autoantibodies. In-depth studies on the pathogenic relevance of autoimmune complement activation in patients are largely lacking. Therefore, the aim of this study was to investigate the pathogenic relevance of complement activation in patients with bullous pemphigoid. Complement activation by autoantibodies in vivo as measured by the intensity of complement C3 deposits in the patients' skin and ex vivo by the complement-fixation assay in serum was correlated with the clinical disease activity, evaluated by Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) and Bullous Pemphigoid Disease Area Index (BPDAI), as well as, with further immunopathological findings in patients with bullous pemphigoid.Results: Complement-activation capacity of autoantibodies ex vivo, but not deposition of complement in the perilesional skin of patients, correlates with the extent of skin disease (measured by ABSIS and BPDAI) and with levels of autoantibodies.Conclusions: Our study provides for the first time evidence in patients for a pathogenic role of complement activation in bullous pemphigoid and should greatly facilitate the development of novel diagnostic tools and of more specific therapies for complement-dependent autoimmune injury

Phenotypic and genetic spectrum of incontinentia pigmenti - a large case series

BACKGROUND AND OBJECTIVES Incontinentia pigmenti is a rare X-linked dominantly inherited systemic disease affecting primarily the skin but also other neuroectodermal tissues such as teeth, hair, eyes, and the central nervous system. PATIENTS AND METHODS This multicenter case series study was conducted at three European departments of Dermatology including 30 patients with incontinentia pigmenti. Twenty patients were evaluated clinically and genetically, another ten only genetically. RESULTS The study included 28 females and two males with a median age of three years. Cutaneous manifestations were present in all 20 patients with clinical data. Stage I was observed in 90 % of those patients. Stage IV was observed as early as one year of age. Dental (81 %), hair (78 %) and neurological anomalies (53 %) were more frequent than previously reported. Fourteen skin biopsies showed typical features of the corresponding stage. Genetic testing of 24 patients revealed the common exon 4-10 deletion in 14 cases and seven other pathogenic variants, including three unpublished mutations. In another three cases, no genetic alterations were found. CONCLUSIONS In this study, the phenotype ranged from only subtle cutaneous involvement to severe multisystemic disorders. Extracutaneous involvement should be evaluated at the time of diagnosis and in regular intervals, as some manifestations may develop over time

Molecular diagnosis of anti-laminin 332 (epiligrin) mucous membrane pemphigoid

Background: Mucous membrane pemphigoid is a group of chronic subepithelial autoimmune blistering diseases that mainly affect mucous membranes. Laminin 332-specific autoantibodies are present in approximately 1/3 of the patients, being associated with an increased risk of malignancy. Because of the severe complications, an early recognition of the disease allowing a timely therapy is essential. The gold standard methods for detection of laminin 332-specific autoantibodies, including the immunoprecipitation and immunoblotting are non-quantitative, laborious and restricted to a few specialized laboratories worldwide. In addition, the use of radioimmunoassays, although highly sensitive and specific, are laborious, expensive and tightly regulated. Therefore, there is a stringent need for a quantitative immunoassay for the routine detection of laminin 332-specific autoantibodies more broadly available to diagnostic laboratories. The aim of this study was to compare different antigenic substrates, including native, recombinant laminin 332 and laminin 332-rich keratinocyte extracellular matrix, for development of an ELISA to detect autoantibodies in mucous membrane pemphigoid. Results: Using a relatively large number of sera from MMP patients with well-characterized autoantibody reactivity we show the suitability of ELISA systems using laminin 332 preparations as adjunct diagnostic tools in MMP. While glycosylation of laminin 332 does not appear to influence its recognition by MMP autoantibodies, ELISA systems using both purified, native and recombinant laminin 332 demonstrated a high sensitivity and good correlation with the detection of autoantibodies by immunoblotting. ELISA systems using different laminin 332 preparations represent a feasible and more accessible alternative for a broad range of laboratories. Conclusions: Our findings qualify the use of immunoassays with the laminin 332-rich preparations as an ancillary diagnostic tool in mucous membrane pemphigoid

The Psoriasis Disability Index in Romanian Psoriasis Patients during COVID-19 Pandemic: Contribution of Clinical and Psychological Variables

Background: Psoriasis is one of the most frequent chronic inflammatory skin diseases and has a negative impact on the interpersonal relationship and psychosocial well-being. The aims of this study were to examine the effects of intensity of pruritus on quality of life and depression, to investigate the relationship between anger, self-esteem, and depression, and to compare patients with early and late onset of psoriasis. As our study was carried out during the COVID-19 pandemic, we aimed also to investigate the safety concerns and anxiety related to COVID-19 in psoriasis patients. Methods: This cross-sectional study included 137 patients diagnosed with plaque psoriasis. The patients were classified as early-onset (age < 30 years) and late-onset psoriasis (age ≥ 30 years). Duration of disease, pruritus scores, and socio-demographic characteristics were recorded. Measures included the State-Trait Anger Expression Inventory (STAXI), Rosenberg Self-Esteem Scale, Beck Depression Inventory (BDI-II), Psoriasis Disability Index (PDI), and Fear and anxiety in relationship with COVID-19 Scale were used for determining anger, anger expression style, self-esteem, depression, anxiety, and quality of life. Results: The psoriasis patients had a lower score for self-esteem than the normative data from the Romanian general population. The average scores for state anger and trait anger are similar to the normative data from the Romanian general population, but the scores for anger-in and anger-out are higher. Patients with early onset had higher depression scores and lower quality of life. Self-esteem correlates negatively with depression, anger, severity of disability due to psoriasis, number of affected areas, and duration of disease. Lower level of self-esteem led to increased anger. Conclusions: Reduced self-esteem, increased anger levels, and depression are present in psoriasis patients. The effective treatment of psoriasis must, therefore, consist of a multidisciplinary approach, in which the personalized treatment of the skin condition is as important as the adjuvant therapies that reduce the patients’ stress level

Additional file 1: of Molecular diagnosis of anti-laminin 332 (epiligrin) mucous membrane pemphigoid

Figure S1. Comparative analysis of serum reactivity with the extracellular matrix and native laminin 332 by ELISA in control patients. Box plots represent optical density measurements of serum reactivity from patients with pemphigus vulgaris (PV, n = 20), epidermolysis bullosa acquisita (EBA, n = 20) and dermatits herpetiformis (DH, n = 20) as well as from healthy donors (n = 4) measured in parallel on native laminin 332 and laminin-rich extracellular matrix of keratinocytes. (PNG 20 kb