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.

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

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

Heterogeneity of antibody response to glomerular basement membrane antigen in patients with different forms of glomerulonephritis.

Antibodies to collagenous and noncollagenous components of glomerular basement membrane (GBM) have been detected by immunoblotting in some sera from patients with various kinds of glomerulonephritis. A half proportion of patients with rapidly progressive glomerulonephritis (RPGN), chronic focal glomerulonephritis (CFGN), idiopathic membranous glomerulonephritis (MGN). IgA nephropathy and lupus nephritis (LE-GN) had IgG antibodies to heterogenous components in acid insoluble fraction of pepsin digested GBM. This acid insoluble fraction represented a complex of collagen and noncollagenous proteins of GBM. Following digestion of acid insoluble fraction with bacterial collagenase, the triple helical collagenous components of GBM were destroyed and released most likely of noncollagenous proteins. Antibodies to this noncollagenous proteins were found in only some patients with chronic glomerulonephritis (17.6%) and lupus nephritis (21.4%). Upon reaction with human placenta derived type IV collagen, different frequencies of antibody response were found in patients of different groups. However, all these reactive sera showed a similar immunoblotting pattern. The relationship between antibody response to antigenic components from human GBM or human placenta and pathogenesis of renal disease is unclear. However, the occurrence of spontaneous autoantibody response to some exposed GBM self antigens may mediate further renal destruction resulting in chronic ongoing stage of the disease.

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

Basement membrane antibodies in Alport's syndrome.

By the indirect immunofluorescent technique, sera from patients with Alport's syndrome showed a reaction with the basement membrane of the capillary wall of glomeruli and peritubular vessels and nearby interstitial tissue of normal monkey and mouse kidney as a substrate. It also revealed bright staining to the matrix surrounding the clusters of EHS tumor cells and stromal tissues. These reactions were caused by autoantibodies present in these sera. These findings were supported by the detection of antilaminin, nidogen and anti collagen type VI in the sera by ELISA method. These evidences suggest that the Alport's patients developed stage of autoimmunity. The exact causes were not so clear, but seemed to be due to multiple factors.

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

Orquitis autoinmune experimental / Experimental autoimmune orchitis

A pesar de los numerosos trabajos realizados en el modelo de orquitis autoinmune experimental (OAE) aún existen varias incógnitas acerca de su patogenia. Clásicamente, la OAE se indujo en cobayos utilizando como antígenos, espermatozoides u homogenado testicular. Nuestro primer interés fue determinar si antígenos no espermáticos como los componentes extracelulares de la pared del túbulo seminífero, utilizados como inmunógenos, eran capaces de inducir un cuadro autoinmune testicular. Obtuvimos, a partir del testículo de la rataÑ a) una preparación rica en membranas basales del túbulos seminífero (STBM) y b) a partir del STBM, una fracción no relacionada al componente colágeno (D-STBM) que demostró poseer determinantes antigénicos comunes con la laminina, principal glicoproteína no colágena de las membranas basales. El 50% de las ratas inmunizadas con STBM, D-STBM o laminina, desarrolaron una lesión testicular moderada, multifocal, caracterizada por leves infiltrados intersticiales, alteraciones de las membranas basales del túbulo seminífero y de la célula de Sertoli, descamación del epitelio germinal y atrofia tubular. También se detectaron anticuerpos circulantes y una respuesta de inmunidad celular específica. A su vez, ratas inyectadas con un suero heterólogo anti-D-STBM desarrollaron una lesión similar. Por otra parte, se indujo una orquitis severa inmunizando ratas Wistar con un hmogenado testicular homólogo y adyuvantes y se estudiaron las poblaciones linfáticas de los ganglios...

Ultrastructure of sciatic nerve of armadillo infected with Mycobacterium leprae.

Ultrastructural observation of sciatic nerves from eight Armadillos were made. Six animals had intravenous inoculation of M. leprae, one had of foot pad, while one had natural leprosy. The available nerves were biopsied at various time sequence ranging from five weeks to twenty four months. Semithin sections did not reveal any neuropathy. Ultrastructurally perineurium was thick and endoneurial collagen was increased. Initially demyelination of non-myelinated fibres was seen in all nerves irrespective of mode of infection. This was followed by demyelination of small myelinated fibres. Active remyelination was predominantly after 17 months. Schwann cell activity was increased and various stages of division were seen. Bacilli were extracellular, intraxonal, in endothelium and in perineurium. Significant observations were on blood vessels. These observations are discussed.