Ectodermal Dysplasia: Association with Anti-Basement Membrane Autoantibodies.

Ectodermal dysplasia (ED) is a group of several genetic conditions with absence or dysgenesis of at least two ectodermal derivatives: teeth, skin and its appendages including hair, nails, eccrine and sebaceous glands. The most important clinical findings in patients with ED are hypodontia, hypotrichosis, and hypohidrosis, which can lead to episodes of hyperthermia. Few reports have focused on the progressive keratopathy in ED. Cicatrizing conjunctivitis associated with anti-basement membrane autoantibodies has been described. We report a series of three ectodermal dysplasia patients with an ocular phenotype typically seen in ocular mucous membrane pemphigoid; conjunctival immunohistopathology revealed anti-basement membrane autoantibodies in all of them, and systemic immunosuppression proved to be effective in improving symptoms and helping to stabilize ocular surface disease.

Linear immunoglobulin A dermatosis: A case report. / Dermatosis inmunoglobulina A lineal: a propósito de un caso.

We present the case of a sixty five year old woman with two months history of pruritus and hyperpigmented annular lesions on the trunk, buttocks and upper extremities. In addition, she presents vesicles with healthy skin on the basis, in the flexor aspect of wrists. No evidence of mucosal involvement. Histological study showed subepidermal vesicular dermatitis with inflammatory infiltrate of neutrophils and eosinophils. Direct immunofluorescence evidenced linear and continuous deposition of immunoglobulin A in basement membrane zone, compatible with linear immunoglobulin A disease.

En este texto se presenta el caso de una paciente de sesenta y cinco años con sintomatología de dos meses de evolución consistente en prurito y lesiones hiperpigmentadas anulares en tronco, glúteos y extremidades superiores. En el área flexora de las muñecas presenta vesículas sobre base eritematosa y piel sana, sin evidencia de compromiso mucoso. Al estudio histológico se constata dermatitis vesicular subepidérmica con infiltrado inflamatorio de neutrófilos y eosinófilos. La inmunofluorescencia directa muestra depósito lineal y continuo de inmunoglobulina A en zona de membrana basal, compatible con dermatosis por inmunoglobulina A lineal.

Immune cell profile in infants' lung tissue.

Little is known about the normal immune cell profile in the lungs of infants without pulmonary disease. Normal lung samples obtained at autopsy of 10 infants that died either due to incidental or inflicted causes or non-pulmonary diseases were stained for antibodies against B and T lymphocytes, macrophages, NK cells, cytotoxic cells, dendritic cells and mast cells. Cells were quantified in the airway epithelial layer, inner layer (between the epithelium and the outer smooth muscle border), outer layer (between the outer smooth muscle border and the external limits of the airway) and alveolar septa. Basement membrane or alveolar septa lengths were assessed by image analysis. Results were expressed as cells/mm. The median age of patients was 6.8 months, ranging from 11 to 840 days. The inner layer of the airways was the region with the smallest density of cells. There was a predominance of cells related to the innate immunity such as CD56+, Granzyme B+ and CD68+ cells in the epithelial layer and alveolar parenchyma. The outer layer and the lung parenchyma presented the highest cellular density. There were very few CD4+ T cells or dendritic cells in most of the lung compartments. The numbers of CD3+ T and granzyme B+ cells correlated positively with age. There was a compartmentalization of immune cells along airways and parenchyma, which may be related to the development of innate and acquired lung defense mechanisms.

Late presentation of Alport posttransplantation anti-glomerular basement membrane disease.

We describe a female patient with Alport disease who developed antiglomerular basement membrane nephritis late after kidney transplantation during the treatment of an acute bacterial pyelonephritis and discuss the potential role of the infection as a trigger for the development of this nephritis.

Autoantibodies to melanocytes and characterization of melanophages in patients affected by a new variant of endemic pemphigus foliaceus.

BACKGROUND: Melanin and melanophages are commonly seen under the basement membrane zone of the skin in patients affected by a new variant of endemic pemphigus foliaceus in El Bagre, Colombia (El Bagre-EPF). OBJECTIVE: Our study was conducted to determine the nature of these pigmentary alterations. METHODS: We utilized clinical, histopathologic and immunologic techniques including direct and indirect immunofluorescence, immunohistochemistry, Bielschowsky staining and immunoelectron microscopy studies. RESULTS: In the El Bagre-EPF patients, we detected dermal melanin in melanophages and antigen-presenting cells, in close proximity to neural and vascular markers. The melanophages consisted of a mixed population expressing CD68, myeloid/histoid antigen and S-100 protein. By immunoelectron microscopy, the presence of autoantibodies in proximity to melanin granules was confirmed within the melanocytes utilizing 10-nm gold particles. CONCLUSION: Dermal antigen-presenting cells, including melanophages, seem to contain a diverse combination of molecules, representative of an immunologic process where these cells are engulfing both autoantigens and/or cellular debris in El Bagre-EPF. Autoantibodies to discrete components of melanocytes were also identified; the clinical and immunologic significance of these findings remains unknown. Our work may provide a possible explanation of a darkened complexion in patients affected by endemic pemphigus foliaceus.

Enfermedad autoinmune: perturbación de la conversación entre la célula blanco (epitelial) y la matriz extracelular / Autoimmune disease: impaired cross-talk between epithelial cell and extracellular matrix

Glándulas salivales de pacientes con síndrome de Sjõgren presentan un aumento en la degradación de componentes de la lámina basal (LB, laminina y colágeno IV) y estroma (colágenos I y III y fibronectina). Estos cambios se correlacionan con un desbalance en la expresión y actividad de metaloproteinasas y sus inhibidores titulares (MMP/TIMP) que desorganiza la LB de acinos y ductos. Esta desorganización es concomitante a una sobreexpresión de lamininas -1 y -5 y a la degradación de nidógenos 1 y -2, que tienen como función establecer puentes de conexión entre laminina y colágeno IV. Cambios post-transcripcionales de la integrina alfa 6 beta 4 están correlacionados con una drástica redistribución de beta 4 en acinos con LB desorganizadas. Estos resultados sugieren que alteraciones en la adhesión célula-matriz y en la formación de contactos célula-célula pueden modificar la señalización de la integrina alfa 6 beta 4 induciendo muerte celular cuando hay una severa interrupción de la célula acinar con la LB.

Increased degradation of basal lamina (BL, laminin and type IV collagen) and stroma (type I and III collagens, and fibronectin) proteins have been observed in salivary glands of patients with Sjõgren’s syndrome. Such changes are associated with imbalanced expression and activity of extracellular matrix metalloproteinases and their tissue inhibitors (MMPs/TIMPs), which contribute to disorganization of the parenchyma basal lamina. Disorganization of the basal lamina is paralleled by an overexpression of laminin-1and -5 and the degradation of nidogens 1 and -2: linker proteins that help maintain the integrity of type IV collagen and laminin networks.Additionally, post-transcriptional changes in alpha 6 beta 4 integrin are associated with a dramatic redistribution of beta 4 in acini, particularly where perturbations in BL organization were apparent. These findings are taken to suggest that changes in acinar cell-matrix adhesion and cell-cell contact formation may alter alpha 6beta 4 integrin signaling, triggering cell death only when severe disruption of cell-BL attachment occurs.

Mechanisms involved in the reduced leukocyte migration in intrauterine undernourishment.

OBJECTIVE: We investigated factors that may be involved in the reduced leukocyte migration observed in intrauterine undernourished rats. METHODS: Male Wistar rat offspring (8-9 wk of age) of dams fed during pregnancy with 50% less food than control dams were used to measure L-selectin expression (by flow cytometry), bone marrow cell count, blood cell count, laminin and type IV collagen in the basal membrane of venules of the spermatic fascia (by immunohistochemistry), total protein level and serum albumin, and the production of leukotriene B4 after stimulation with tumor necrosis factor-alpha and corticosterone plasma levels (by enzyme-linked immunosorbent assay). RESULTS: Hypocellularity in bone marrow and peripheral blood and reduced L-selectin expression were found in the undernourished rat offspring (UR) compared with nourished offspring (NR; P < 0.05). Type IV collagen in the basal membrane of the venules of the spermatic fascia was less in UR than in NR (P < 0.05). The total protein levels and serum albumin did not differ between the two groups. Leukotriene B4 production after stimulation with tumor necrosis factor-alpha was lower in UR (P < 0.05). These differences could not be attributed to circulating glucocorticoids levels, which were not different in the NR and UR groups. CONCLUSION: Our data suggest that all observed differences contribute to reduced leukocyte migration in undernourishment.

Immunopathologic study of erythema dyschromicum perstans (ashy dermatosis).

Erythema dyschromicum perstans (EDP) is a pigmentary disease of unknown etiology in which damage to basal cells is thought to be mediated by adhesion molecules. The aim of this study was to characterize the histopathology and immunopathology of EDP. Forty-three patients from Medellín, Colombia, with the diagnosis of EDP were evaluated. Skin biopsy specimens were obtained for histopathology and immunohistochemistry, using monoclonal antibodies directed against the following markers: CD4, CD8, CD56, CD1a, CD68, CLA, HLA-DR, ICAM-1 and LFA-1alpha. A dermal lymphocytic infiltrate was observed in all cases, with a perivascular location in 86%. Other histologic features included melanophages in all specimens, vacuolization of the basement membrane zone (BMZ) 58% and exocytosis of lymphocytes (53.5%). The mean number of total leukocytes was 1510 cells mm-2 of tissue. There was a predominance of CD8+ T lymphocytes in the dermis and HLA-DR+, ICAM-1+ keratinocytes in the epidermis. Exocytosis of cutaneous lymphocyte antigen (CLA)+cells was observed in areas of BMZ damage, suggesting that response to antigenic stimulation may play a role in the development of EDP.

Basal lamina disorganisation of the acini and ducts of labial salivary glands from patients with Sjogren's syndrome: association with mononuclear cell infiltration.

OBJECTIVE: To study the expression of laminin and type IV collagen as biomarkers of the organisation of the basal lamina of acini and ducts in labial salivary glands from patients with Sjögren's syndrome, and to relate this organisation to inflammatory cell invasion of acini and ducts. METHODS: Immunohistochemistry for laminin and type IV collagen was undertaken on sections of labial salivary glands from 30 patients with Sjögren's syndrome, 10 control subjects, and 24 controls with chronic sialoadenitis. Immunohistochemistry reaction, alterations to cell morphology, and the presence of inflammatory cells in acini and ducts were evaluated and scored using a semiquantitative method. RESULTS: Changes in the expression of laminin and type IV collagen in the basal lamina of acini and ducts of labial salivary glands from patients with Sjögren's syndrome were more pronounced than in labial salivary glands from control groups. A remarkable characteristic was the disorganisation of the basal lamina in the labial salivary glands in Sjögren's syndrome. The pattern of immunoreactivity of the basal lamina of other structures (for example, blood vessels) did not change. In Sjögren's syndrome, invasion of cytotoxic T lymphocytes was only observed in acini and ducts which had a disorganised basal lamina. CONCLUSIONS: The high state of disorganisation of the basal lamina of acini and ducts could allow invasion of cytotoxic T lymphocytes in Sjögren's syndrome, contributing to cell death and ductal hyperplasia.

Doença da IgA linerar - Revisão da Literatura / Linear IgA disease - literature review

A doença por depósito linear de imunoglobulina A (IgA) é um processo mucocutâneo crônico, raro e de origem auto-imune, caracterizado por depósitos lineares do anticorpo ao longo da membrana basal da pele e mucosas. O estudo da enfermidade é de grande importância, visto que a mesma é de complexo diagnóstico e tratamento, além de sua etiopatogenia não estar ainda definida. O presente artigo teve por objetivo revisar a literatura referente à doença da IgA linear, abordando suas características clínicas, diagnóstico diferencial e alternativas de tratamento

Parkinsonian features after streptococcal pharyngitis.

Bradykinesia and rigidity developed in a 10-year-old girl during an episode of Sydenham chorea. These parkinsonian features improved over 6 months. Serum analysis demonstrated elevated anti-streptolysin-O and anti-basal ganglia antibodies. We suggest that autoimmune antibodies may cause remitting parkinsonian signs subsequent to streptococcal tonsillitis as part of the spectrum of poststreptococcal CNS disease.

[The syndrome of renal and pulmonary vasculitis with positive neutrophil anticytoplasmic antibodies and antibasement membrane antibodies. A case report]. / Síndrome de vasculitis renal y pulmonar con anticuerpos anticitoplasma de neutrófilos y anticuerpos antimembrana basal positivos. Informe de un caso.

The authors present a case of Goodpasture's syndrome with necrotizing vasculitis of spleen and appendix. Serological examination shows antiglomerular basement membrane antibodies and antineutrophil cytoplasmic antibodies. The authors review the literature to establish if this or other similar cases can be considered a distinct disease entity. The authors also mention the laboratory methods that are currently being used to classify more precisely the vasculitides associated with glomerulonephritis.

Síndrome de vasculitis renal y pulmonar con anticuerpos anticitoplasma de neutrófilos y anticuerpos antimembrana basal positivos: informe de un caso / The syndrome of renal and pulmonary vasculitis with positive neutrophil anticytoplasmic antibodies and antibasement membrane antibodies: a case report

The authors present a case of Goodpasture's syndrome with necrotizing vasculitis of spleen and appendix. Serological examination shows antiglomerular basement membrane antibodies and antineutrophil cytoplasmic antibodies. The authors review the literature to establish if this or other similar cases can be considered a distinct disease entity. The authors also mention the laboratory methods that are currently being used to classify more precisely the vasculitides associated with glomerulonephritis

Cutaneous lupus erythematosus: direct immunofluorescence and epidermal basal membrane study.

Biopsy specimens of cutaneous discoid lesions of 71 patients with cutaneous lupus erythematosus (CLE) were studied. The material was examined by direct immunofluorescence (DIF) to establish positivity and morphologic patterns of immunoglobulins and complement deposits in the basement membrane zone (BMZ). A correlation between DIF results and thickening of the epidermis basement membrane (BM) stained by periodic acid-Schiff (PAS), obtained from 31 matched biopsy specimens, also is presented. Direct immunofluorescence had positive results in 66.20% of the 71 examinations and 70.97% of the matched examinations, whereas PAS showed BM thickening in 100% of the specimens. This observation stresses the importance of such histopathologic findings in the diagnosis of discoid lesions in CLE. There was no correlation between DIF patterns and PAS-stained BMZ thickening. These findings merit additional study. In conclusion, an accordance between PAS-stained BM thickening and immunoglobulin deposits has occurred in 70.97% of cases. This phenomenon does not depend on the presence of immunocomplexes, for it occurs even in cases in which immunocomplex deposits were not detected.

The long-term evolution of immune deposits in passive Heymann nephritis.

1. To study the long term course of passive Heymann nephritis (PHN), 42 adult male Wistar rats were injected with rabbit anti-FX1A serum (PHN group) and 42 rats received normal rabbit serum (control group). Two animals from each group were sacrificed 2 weeks after the inoculation and 10 animals each from the control and PHN groups were sacrificed 4, 13, 25 and 53 weeks later. 2. The PHN group exhibited a significant elevation in 20-h proteinuria which lasted from the first week (control group, 9.19 +/- 0.87; PHN group, 25.3 +/- 2.66) to the 25th week (control group, 22.6 +/- 2.15; PHN group, 66.7 +/- 10.4) except for week 17. From week 29 to week 53 there was no statistical difference between the 2 groups. 3. Light microscopy showed no difference between the kidneys of PHN and control rats. Immunofluorescence microscopy in PHN rats showed granular deposition of autologous and heterologous IgG on the glomerular basement membrane (GBM), whose intensity and pattern did not change during 53 weeks of observation. 4. When examined by electron microscopy the glomeruli of PHN rats showed: a) electron-dense deposits which were initially subepithelial and homogeneous and later intramembranous, granular and often surrounded by an electron-transparent halo; b) focal thickening of the GBM at the sites of intramembranous deposits; c) effacement of podocytes located close to the deposits; d) "penetration" of the podocytes into the GBM associated with the deposits; e) presence of osmiophilic granules in the cytoplasm of the podocytes located inside the GBM similar to the granules of the deposits next to them. The association of the penetration of the podocytes into the GBM with the deposits and the presence of the osmiophilic granules inside the foot process have not been described previously in PHN.

Doença de Goodpasture: hemorragia pulmonar e glomerulonefrite mediadas por anticorpos antimembrana basal / Goodpasture's disease: antibasement membrane antibody mediated hemorrhagic pneumonitis and glomerulonephritis

Doença de Goodpasture tem sido o nome proposto como o mais adequado para denominar a doença induzida por auto-anticorpos antimembrana basal que se manifesta clinicamente com hemorragia pulmonar e glomerulonefrite. Nesta revisäo säo apresentados conceitos atuais sobre aspectos clínicos, laboratoriais, etiopatogênicos e terapêuticos dessa doença

Identification and characterization of highly conserved antigenic determinants in the laminin molecule.

1. Fragments P1 and E8, the result of two different enzymatic digestions of the laminin molecule, represent interaction sites of laminin with specific cell receptors. By using negative and positive affinity purification of a rabbit antiserum against mouse laminin we have generated antibodies to these two fragments. 2. Antibodies against P1 were able to immunoprecipitate fragment E8 from elastase-digested laminin. By liquid phase competition experiments we demonstrated that the epitopes shared by P1 and E8 are a minor portion of the antigenic determinants of P1. When we checked for the presence of these shared epitopes in the human laminin molecule, they were the major fraction of the interspecies antigenic conservation. 3. A similar approach using polyclonal antibodies against human laminin has confirmed these results. 4. The shared epitopes present in both mouse and human laminin molecules seem to be spatially determined, because antibodies against these sites did not bind to fully denatured laminin. 5. Since human and mouse laminin bind to cell receptors and to other extracellular matrix proteins from both species, we conclude that these antigenic determinants may represent the actual sites for at least some of these interactions.

Identification and characterization of highly conserved antigenic determinants in the laminin molecule

1. Fragments P1 and E8, the results of two different enzymatic digestions of the laminin molecule, represent interaction sites of laminin with specific. By using negative and positive affinity purification of a rabbit antiserum against mouse laminin we have generated antibodies to these two fragments. 2. Antibodies against P1 were able to immunoprecipitate fragment E8 from elastase-digested laminin. By liquid phase competition experiments we demonstrated that the epitopes shared by P1 and E8 are a minor portion of the antigenic determinants of P1. When we checked for the presence of these shared epitopes in the human laminin molecule, they were the major fraction of the interspecies antigenic conservation. 3. A similar approach usisng polyclonal antibodies against human laminin has confirmed these reults. 4. The shared epitopes present in both mouse and human laminin molecules seem to be spatially determined, because antibodies against these sites did not bind to fully denatured laminin. 5. Since human and mouse laminin bind to cell receptors and to other extracellular matrix proteins from both species, we conclude that these antigenic determinants may represent the actual sites for at least some of these interactions