Concomitancia de anticuerpos antimembrana basal y ANCA en el síndrome riñón-pulmón / Concomitance of glomerular basement membrane antibodies and ANCA in pulmonary - renal syndrome

La enfermedad antimembrana basal glomerular (anti-MBG) es una condición que se manifiesta clínicamente como glomerulonefritis rápidamente progresiva y hemorragia alveolar, también llamada Síndrome Riñón- Pulmón. Se asocia a la presencia de autoanticuerpos dirigidos contra el colágeno tipo IV de la membrana basal glomerular. Las vasculitis sistémicas asociadas a ANCA también pueden manifestarse como Síndrome Riñón-Pulmón, cuadro clínico a veces indistinguible de la enfermedad anti-MBG. La concomitancia de ANCA y anticuerpos anti-MBG en el Síndrome Riñón-Pulmón es del orden de un 30 por ciento, según distintos reportes de la literatura. El perfil clínico, el pronóstico y el rol fisiopatológico de cada anticuerpo en este grupo de pacientes todavía son materia de investigación. El mecanismo patogénico inicial parece ser el daño mediado por ANCA, que puede inducir la aparición de anticuerpos anti-MBG, los que perpetúan el daño en el glomérulo.

Anti-glomerular basement membrane (anti-MBG) disease is a condition that is manifested clinically as rapidly progressive glomerulonephritis and alveolar hemorrhage, also known as Pulmonary-Renal Syndrome. It is associated with the presence of autoantibodies directed against type IV collagen of the glomerular basement membrane. Systemic vasculitis associated with ANCA may also manifest as Pulmonary-Renal Syndrome, sometimes clinically indistinguishable from the anti-MBG disease.The concomitance of ANCA and anti-MBG antibodies in the Pulmonary-Renal Syndrome is about 30 percent, according to various reports in literature. The clinical profile, prognosis and physiopathologic roles of each antibody in this group of patients is still under investigation. The pathogenic mechanism appears to be the initial damage mediated by ANCA, which may induce the appearance of anti-MBG, those who perpetuate the glomerulus damage.

Revisão: Glomerulopatia aguda do transplante renal / Acute allograft glomerulopathy

A glomerulopatia aguda do transplante (GATR) refere-se à inflamação do glomérulo nos três primeiros meses pós-transplante, em decorrência de reações irnunológicas. É caracterizada por hipercelularidade glomerular, às custas de células linfomononucleares e entumecimento e proliferação de células endoteliais e mesangiais. Os vários estudos relatam ocorrência da glomerulite entre 4,3 por cento a 14 por cento dos enxertos renais. Na presente revisão, as investigações sobre a patogenia, imunofenotipagem das células infiltrantes, eventual associação com citomegalovírus (CMV) ou com episódios de rejeição aguda, e o impacto na sobrevida do enxerto são criticamente revistas. A GATR é entendida com um componente da rejeição aguda, mediada por linfócitos T, particularmente citotáxicos. A imunofenotipagem das células infiltrantes revela exsudato rico em linfácitos T, monácitos, células NK e raros linfácitos B. A associação de GATR com CMV é assunto ainda controverso, apesar da maioria dos trabalhos recentes não suportar esta correlação. É freqüente a ocorrência simultânea de GATR com rejeição aguda vascular. Porém, há casos de GATR isolada, sugerindo que a glomerulite tem mecanismo patogenético provavelmente distinto de rejeição. A GATR, na maioria dos estudos, mostrou ter impacto negativo na sobrevida do enxerto. Não está ainda totalmente esclarecido até onde esses resultados se devem à GATR por se e qual sua associação com o processo de rejeição. Estudos adicionais são ainda necessários para melhor conhecer os mecanismos patogenéticos da GATR, sua relação com rejeição e com a sobrevida do enxerto.

Immune complex mediated lesions in experimental Kala azar: an ultrastructural study.

Immune complexes play an important role in causation of renal lesions in various diseases. Circulating immune comlexes (CIC) are described in Kala azar. Role of CIC in pathogenesis of Kalaazar is discussed in present study. BALB/C mice were experimentally infected with L. donovani promastigotes. After visceralisation of infection, sera and kidneys of infected mice were preserved. Leishmanial antigen specific CIC could be demonstrated in 100% of infected mice by PEG ELISA, while they were absent in control mice. Ultrastructural pattern of renal lesions in infected mice showed presence of focal small electron dense deposits in glomerular basement membrane and subepithelial space, resembling immune complexes (humps). Rarely subendothelial and mesangial hypercellularity was present. These findings point towards a definite role of CIC in pathogenesis of renal lesions in Kalaazar.

Crescentic glomerulonephritis: a clinicopathologic analysis of 17 cases with emphasis on glomerular and interstitial neutrophil infiltration

In order to determine the extent to which specific forms of glomerulonephritis (GN) contribute to the pool of crescentic GN, renal tissues from 17 crescentic GN patients were examined with special attention to glomerular and interstitial neutrophil infiltration. Renal tissues from five normal kidneys served as normal controls. Renal biopsy tissues from five patients with postinfectious GN in which crescent formation was not observed were also examined as disease controls. The patients were put into both three groups according to immunofluorescence findings and two groups according to the active or inactive phase of the crescents: group 1 with anti-glomerular basement membrane crescentic GN, one case; group 2 with immune complex crescentic GN, ten cases; and group 3 with pauci-immune crescentic GN, six cases. Four of the nine individuals tested were positive for anti-neutrophil cytoplasmic antibody (44.4%). Glomerular and interstitial neutrophil infiltrations were prominent in both the active and inactive phase groups, compared to normal controls (p<.05). Glomerular neutrophil infiltration was significantly prominent in the active phase group, compared to the inactive phase group (p<.001). In both the active and inactive phase groups, interstitial neutrophil infiltration was prominent, compared to disease control groups (p<.05). These results support the concept of the participation of periglomerular leukocytes in the renal tissue damage of crescentic GN, although the role of neutrophils was not examined.

Mesangial proliferative glomerulonephritis in chronic obstructive pulmonary disease.

Ten patients of chronic obstructive pulmonary disease were studied for changes in ultrastructure of the glomeruli, serum immunoglobulin and complement levels. The glomeruli showed proliferation in the mesangium in 90% patients and electron dense deposits in the mesangium in 30% patients. IgA and IgG were usually elevated whereas complements were usually depressed in most of these patients. It is suggested that repeated respiratory infections in these subjects may be responsible for mesangioproliferative type of glomerulonephritis, high IgA and IgG levels. The complements are activated and they take part in immune complex formation getting deposited in mesangium.

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

Glomerular alterations in idiopathic haematuria--ultrastructural and morphometric analysis.

Re-evaluation of kidney biopsies has been done along with morphometric analysis of glomerular basement membrane thickness (G.B.M.) in 41 cases of idiopathic haematuria, in whom the initial routine light, immunofluorescent and electron microscopic examination had not shown any significant alterations. Extreme attenuation of G.B.M. (mean thickness of 2581 +/- 488 A) had been found in thirty one patients in contrast to mean GBM thickness of 4295 +/- 470 A found in control group. Absence of any history of familial haematuria in these patients distinguished them from hereditary nephropathies and hence categorized under the term thin basement membrane nephropathy. Follow up of these patients for upto 8 years had shown persistence of symptoms without further deterioration of renal function as well as morphology.

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.