Paweł Bartkiewicz

Bullous pemphigoid and neurodegenerative diseases: a study in a setting of a Central European university dermatology department

Bullous pemphigoid (BP) is an autoimmune blistering dermatosis of the elderly mediated by IgG and IgE antibodies to skin hemidesmosomal proteins, BP180 and/or BP230, that occur physiologically also in neuronal tissue. It was reported that BP is associated with neurodegenerative diseases (ND). We performed a retrospective study in a setting of a Central European university dermatology department on prevalence of ND in 94 BP patients. 26 out of 94 BP patients had at least one ND. ND included: Parkinson’s disease, dementia, stroke, hear loss, tinnitus, blindness, vertigo, neurosyphilis, systemic sclerosis, and epilepsy. Since population aging is conceivably responsible for the rising number of BP cases as a result of immunosenescence-related phenomena, the plausible BP-specific immunopathogenetic relationship between BP and ND deserves to be further experimentally explored.

Analysis of the autoimmune response against BP180 and BP230 in ethnic Poles with neurodegenerative disorders and bullous pemphigoid

Recent studies postulated the association between bullous pemphigoid (BP) and neurodegenerative disorders (ND). The autoantibodies to BP180 and/or BP230 may be present not only in BP, but also in ND as neuronal isoforms of these proteins are identified in the central nervous system. However, there are only scant data about the precise pathogenetic mechanisms interlinking ND and BP as well as the immunologic profile in these patients. The aim is to analyze the serological immunopathological profiles (anti-BP180 IgG, anti-BP230 IgG) in BP patients with and without ND in order to identify the specific autoantibody(ies) and corresponding antigens responsible for ND development in BP patients. Altogether, 82 ethnic Poles with BP and their medical records were examined (62 BP-ND; 20 BP+ND). Levels of serum anti-BP180/BP230 IgG in BP patients were evaluated with ELISAs. The statistical analyses involved Pearson chi-squared test, Mann-Whitney U-test and ranking of autoantibodies. The prevalence of ND among BP patients was 24.4%. There were no statistically significant differences in autoantigens profiles (anti-BP180/anti-BP230 IgG) between BP+ND and BP-ND groups. There was no relationship between ND development and anti-BP180/anti-BP230 IgG level (p = 0.5933, p = 0.4701, respectively). The autoantibodies levels of BP+ND and BP-ND patients show insignificant differences suggesting that also in ethnic Poles a hypothetical pathogenetic association of BP and ND, but not only an aging-related epidemiological one, appears to be independent of a particular BP antigen. Nevertheless, it cannot be excluded that phenomena of epitopes spreading, immune cross-reaction and conformational changes in BP180/BP230 may underlie BP development in ND patients.

Neurodegenerative disorders, bullous pemphigoid and psoriasis: a comparative study in ethnic Poles indicates that Parkinson’s disease is more relevant to bullous pemphigoid

Introduction Bullous pemphigoid (BP) is an autoimmune blistering dermatosis of the elderly with autoimmunity to hemidesmosomal proteins, BP180 and BP230, which are expressed also in neuronal tissue. Aim The aim here was to retrospectively compare the prevalence of neurodegenerative disorders (ND), particularly Parkinson’s disease (PD), unspecified conditions manifesting as dementia and stroke, in two groups of ethnic Poles, with BP and with psoriasis (Ps), in order to obtain data whether BP is more prone to coexist with ND than Ps in the elderly. Psoriasis was chosen in this comparative study as it was considered to be a paradigm of cutaneous disease with systemic manifestations. Material and methods The available medical records of 96 BP patients and 149 Ps patients over 70 years of age were analyzed for the presence of ND. Results There were no statistically significant differences in prevalence of ND without specifying the type and ND types analyzed between BP and Ps groups, except for a higher prevalence of PD in the BP group. Conclusions Thus, regarding population aging and increasing incidence and prevalence of BP corresponding with that phenomenon in various ethnicities, it appears justified to expand studies of a possible immunopathogenic relationship, appearing to be PD-related, between BP and ND.

Reviewing putative industrial triggering in pemphigus: cluster of pemphigus in the area near the wastewater treatment plant

A range of pemphigus is relatively rare potentially fatal group of autoimmune blistering dermatoses. Usually, there is no apparent triggering, while in some predisposed patients there are alleged environmental/industrial inducing factors. In a short time period (4 years), we diagnosed 3 novel cases of pemphigus (1 pemphigus vulgaris, 1 pemphigus foliaceus and 1 shift from pemphigus foliaceus into pemphigus vulgaris) at a clinical and laboratory level (ELISA, immunofluorescence studies). We discuss a possible common inducing mechanism as these patients inhabit one estate of the Poznan suburbia (Kozieglowy, population < 12,000), Greater Poland district, Poland, and review literature data on alleged pemphigus triggers. To the best of our knowledge, this is the first report exploring the putative association between pemphigus diseases and wastewater treatment plant waterborne or volatile by-products in the vicinity of such a facility.

Clinical evaluation of a multiparametric ELISA as a rapid tool for routinely diagnosing IgG-mediated autoimmune blistering dermatoses in ethnic Slavs

Technical innovation of autoimmune blistering dermatoses (ABDs) diagnosis aimed at multiplex approach. Two multiparametric ELISA tests are commercially available for ABDs serology. The aim was to compare diagnostic accuracy of multiparametric and monospecific ELISAs and to examine the diagnostic value/agreement of multivariant ELISA in compliance with traditional diagnostic setup for ABDs.

Acute-phase response and its biomarkers in acute and chronic urticaria

Introduction Since urticaria is a persisting inflammatory disease it is important to establish the prognostic factors for the duration and severity of the disease. Aim To evaluate serum concentrations of selected acute-phase proteins (APP) in patients with various forms of urticaria as compared to healthy volunteers and also to analyze these concentrations in different types of urticaria. Additionally, to evaluate the correlation between serum levels of selected APP and disease activity. Material and methods Serum concentrations of C-reactive protein (CRP), α1-acid glycoprotein (AGP), α1-antichymotrypsin (ACT), α1-antitrypsin (AT), ceruloplasmin (Cp), transferrin (Tf), α2-macroglobulin (α2M) and haptoglobin (Hp) were measured. Quantitative measurement was conducted using the rocket immunoelectrophoresis. Disease activity was assessed with the use of total symptom score. Results Analysis of serum APP concentrations revealed statistically higher serum concentrations of CRP, AGP and ACT in the entire group of patients with urticaria in comparison with the control group. In the entire group of patients with urticaria, CRP, AGP, ACT, Cp and Hp correlated positively with disease activity, intensity of pruritus and the number and size of urticarial wheals. Statistically lower serum concentrations of CRP, ACT, Cp and Hp were detected in the group of patients with acute urticaria (AU) and angioedema together, compared to the patients suffering from AU only. Conclusions Patients with symptoms of various forms of urticaria present a distinct profile of serum APP concentrations. A significant correlation observed between CRP, AGP, ACT, Cp, Hp and clinical activity score points to the potential role of APP as markers of the urticarial activity.

A comparative study of expression of Fc receptors in relation to the autoantibody-mediated immune response and neutrophil elastase expression in autoimmune blistering dermatoses

Here we investigated the cutaneous CD32A and CD89 expression in relation to the neutrophil elastase (NE) expression and serum level of anti-desmoglein 1 and 3 (DSG1/DSG3) IgG in pemphigus, anti-BP180/BP230 IgG in bullous pemphigoid (BP), anti-gliadin nonapeptides (npG), tissue (tTG), and epidermal transglutaminases (eTG) IgA in dermatitis herpetiformis (DH). The examined material consisted of skin/mucosal tissues and sera. In total, 87 patients were studied. Immunohistochemistry on paraffin-embedded sections with quantitative digital morphometry was used to measure the intensity of CD32A/CD89/NE expressions. Levels of anti-DSG1/DSG3 IgG, anti-BP180/BP230 IgG, and anti-npG/tTG/eTG IgA were evaluated with ELISAs. CD32A was abundantly expressed in cutaneous lesions in pemphigus and BP. We found no statistically significant correlation between the CD32A/CD89 and NE expression intensities in pemphigus, BP, and DH. There was a significant correlation between CD89 expression and anti-npG IgA in DH. Our results revealed a lack of correlation between CD32A expressions and anti-DSG1/DSG3 IgG levels in pemphigus, anti-BP180/BP230 IgG in BP as well as CD89 expression and anti-tTG/eTG IgA in DH. CD89 seems to be linked with gluten intolerance in DH rather than with proteolytic destruction of dermal-epidermal junction. CD32A appears to play an important role in mediating skin injury in pemphigus and BP, but probably independently from specific autoantibodies.