A unique form of endemic pemphigus in northern Colombia

Velez, Ana Maria Abreu; Hashimoto, Takashi; Bollag, Wendy B.; Tobón‐Arroyave, Sergio Iván; Abrèu-Velez, Clara Eugenia; Londoño, Martha Luz; Montoya, Fernando; Beutner, Ernst H.

doi:10.1067/s0190-9622(03)00851-x

Cited by 80 publications

(133 citation statements)

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“…We also utilized 15 control skin biopsies from cosmetic surgery patients in the USA, taken from the chest and/or abdomen. The Bagre-EPF patients were previously diagnosed by us, fulfilling specific criteria as previously documented [6][7][8][9][10]. We also tested another group of ABD patients, whose skin biopsies were obtained from the archival files of two private dermatopathology laboratories in the USA.…”

Section: Subjects Of Studymentioning

confidence: 99%

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Tissue inhibitor of metalloproteinase 1, matrix metalloproteinase 9, αlpha-1 antitrypsin, metallothionein and urokinase type plasminogen activator receptor in skin biopsies from patients affected by autoimmune blistering diseases

Velez¹,

Naranjo²,

Ávila³

et al. 2013

Our Dermatol Online

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Introduction: Proteinases and proteinase inhibitors have been described to play a role in autoimmune skin blistering diseases. We studied skin lesional biopsies from patients affected by several autoimmune skin blistering diseases for proteinases and proteinase inhibitors. Methods: We utilized immunohistochemistry to evaluate biopsies for α-1-antitrypsin, human matrix metalloproteinase 9 (MMP9), human tissue inhibitor of metalloproteinases 1 (TIMP-1), metallothionein and urokinase type plasminogen activator receptor (uPAR). We tested 30 patients affected by endemic pemphigus, 30 controls from the endemic area, and 15 normal controls. We also tested 30 biopsies from patients with bullous pemphigoid (BP), 20 with pemphigus vulgaris (PV), 8 with pemphigus foliaceus, and 14 with dermatitis herpetiformis (DH). Results: Contrary to findings in the current literature, most autoimmune skin blistering disease biopsies were negative for uPAR and MMP9. Only some chronic patients with El Bagre-EPF were positive to MMP9 in the dermis, in proximity to telocytes. TIMP-1 and metallothionein were positive in half of the biopsies from BP patients at the basement membrane of the skin, within several skin appendices, in areas of dermal blood vessel inflammation and within dermal mesenchymal-epithelial cell junctions.Key words: endemic pemphigus foliaceus; autoimmune blistering skin diseases; matrix metalloproteinase 9; tissue inhibitor of metalloproteinases 1; urokinase type plasminogen activator receptor; α-1-antitrypsin IntroductionMultiple theories have been proposed regarding the pathophysiology of cutaneous autoimmune blistering skin diseases (ABDs). Some involve plasminogen activation, desmoglein compensation, acetylcholine receptor antibodies, and intracellular signal control of autoantibodies [1]. Moreover, human autoantibodies and the presence of complement are primary factors in producing the blisters of human autoimmune skin blistering diseases and are thought to exert their pathogenic effect via proteases [2,3]. Few studies have tested for proteases and protease inhibitors in lesional skin from patients affected by ABDs [4,5]. We decided to investigate enzymes that could be modulated by ions that have been postulated as triggers for ABDs. We also aimed to investigate enzymes that are related to xenobiotics, based on our previous findings of metals and metalloids in skin biopsies of patients with a new variant of endemic pemphigus foliaceus in El Bagre, Colombia (El-Bagre-EPF) that are exposed to significant mercury pollution [5]. Thus, we utilized immunohistochemistry (IHC) to test for anti-human-α-1-antitrypsin, anti-human matrix metalloproteinase 9 (MMP9), anti-human tissue inhibitor of metalloproteinases 1 (TIMP1), urokinase type plasminogen activator receptor (uPAR) and for metallothionein in patients affected by autoimmune skin blistering diseases.

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Section: Subjects Of Studymentioning

confidence: 99%

“…The organs from the autopsies were taken within 12 hours of patient death. The direct immunofluoresecent studies (DIF) were performed as previously described [6][7][8][9][10].…”

Section: Immunohistochemistry Stainingmentioning

confidence: 99%

Tissue inhibitor of metalloproteinase 1, matrix metalloproteinase 9, αlpha-1 antitrypsin, metallothionein and urokinase type plasminogen activator receptor in skin biopsies from patients affected by autoimmune blistering diseases

Velez¹,

Naranjo²,

Ávila³

et al. 2013

Our Dermatol Online

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“…In addition to these patterns, we added the following: upper dermal blood vessel perivascular staining (UVS), neurovascular staining around skin appendageal structures (NVS), endothelial-mesenchymal cell junction-like staining (EMCJ), dermal cell junction staining (DCS) and peritelocyte staining (ATS) [11]. Our IHC staining was performed as previously described before [7][8][9][10]. For IHC, all antibodies utilized were obtained from Dako(Carpinteria, California, USA).…”

Section: Quantificaton Of Staining Intensity To Obtain Precise Data Omentioning

confidence: 99%

Immunohistochemistry versus immunofluoresence in the diagnosis of autoimmune blistering diseases

Velez¹,

Howard²

2013

Our Dermatol Online

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Introduction: In patients with autoimmune skin blistering diseases (ABDs), the diagnostic gold standard has classically been direct and indirect immunofluorescence (DIF and IIF), despite inherent technical problems of autofluorescence. Aim: We sought to overcome autofluorescence issues and compare the reliability of immunofluorescence versus immunohistochemistry (IHC) staining in the diagnoses of these diseases. Methods: We tested via IHC for anti-human IgG, IgM, IgA, IgD, IgE, Kappa light chains, Lambda light chains, Complement/C3c, Complement/ C1q, Complement/C3d, albumin and fibrinogen in 30 patients affected by a new variant of endemic pemphigus foliaceus in El Bagre, Colombia (El Bagre-EPF), and 30 control biopsies from the endemic area. We also tested archival biopsies from patients with ABDs whose diagnoses were made clinically, histopathologically and by DIF/IIF studies from 2 independent dermatopathology laboratories in the USA. Specifically, we tested 34 patients with bullous pemphigoid (BP), 18 with pemphigus vulgaris (PV), 8 with pemphigus foliaceus (PF), 14 with dermatitis herpetiformis (DH) and 30 control skin samples from plastic esthetic surgery reduction surgeries. Results: The diagnostic correlation between IHC and DIF-IIF was almost 98% in most cases. IHC revealed evidence of autofluorescence around dermal blood vessels, dermal eccrine glands and neurovascular packages feeding skin appendices in ABDs; this autofluorescence may represent a non-specific immune response. Strong patterns of positivity were seen also in endothelial-mesenchymal cell junction-like structures, as well as between dermal fibrohistiocytic cells. In PV, we noted strong reactivity to neurovascular packages supplying sebaceous glands, as well as apocrine glands with edematous changes. Conclusions:We suggest that IHC is as reliable as DIF or IIF for the diagnosis of ABDs; our findings further suggest that what has previously been considered DIF/IIF autofluorescence background may be of relevance in ABDs. Our discovery of reactivity against edematous dermal apocrine glands may be related to the fact that PV has a vegetant form, with lesions present in anatomic areas where these glands exist.

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“…These auto-Abs induce the loss of adhesion between KCs, leading to the formation of intraepithelial blisters of the skin [14]. Other endemic foci of PF have been identified in the rural regions of Colombia [15] and Tunisia [16]. The onset and course of PF depend on both genetic predisposing and exogenous inducing factors.…”

Section: Introductionmentioning

confidence: 99%

Potential Role of TLR Ligand in Aethiopathogenesis of Tunisian Endemic Pemphigus Foliaceus

D¹

2013

Biochem Physiol

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Pemphigus foliaceus (PF) is an autoimmune skin disease in which environmental factors are thought to participate. Recent studies suggest that microbial components use signaling molecules of the human Toll-like receptor (TLR) family to transduce signals in keratinocytes. The aim of our research was to investigate the expression of TLRs 2, 3 and 4 by keratinocytes of PF patients compared to normal keratinocytes, in order to characterise the nature of the microbial factor involved in the etiopathology of PF. Biopsies obtained from 43 PF patients and 20 healthy controls were assessed by immunohistochemical analysis using specific polyclonal antibodies. The TLR2, TLR3 and TLR4 expression was significantly upregulated in PF epidermis. The significant increase of those TLRs simultaneously may merely reflect the complicated environmental conditions of rural women in the southern rural regions of Tunisia. Interestingly, we have found that the TLR4 diffuse expression was associated with the production of anti-desmoglein 1 Abs (p=0.037). This could be in line with a potential role of TLR ligand in aethiopathogenesis of Tunisian endemic PF.TLR over-expression in pemphigus skin indicates that TLRs are involved in the pathogenesis of pemphigus through stimulation by infectious or endogenous ligands.

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A unique form of endemic pemphigus in northern Colombia

Cited by 80 publications

References 20 publications

Tissue inhibitor of metalloproteinase 1, matrix metalloproteinase 9, αlpha-1 antitrypsin, metallothionein and urokinase type plasminogen activator receptor in skin biopsies from patients affected by autoimmune blistering diseases

Tissue inhibitor of metalloproteinase 1, matrix metalloproteinase 9, αlpha-1 antitrypsin, metallothionein and urokinase type plasminogen activator receptor in skin biopsies from patients affected by autoimmune blistering diseases

Immunohistochemistry versus immunofluoresence in the diagnosis of autoimmune blistering diseases

Potential Role of TLR Ligand in Aethiopathogenesis of Tunisian Endemic Pemphigus Foliaceus

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