RESUMEN
The most prevalent severe manifestation of systemic lupus erythematosus is nephritis, which is characterized by immune complex deposition, inflammation, and scarring in glomeruli and the tubulointerstitium. Numerous studies indicated that glomerulonephritis results from a systemic break in B cell tolerance, resulting in the local deposition of immune complexes containing Abs reactive with ubiquitous self-Ags. However, the pathogenesis of systemic lupus erythematosus tubulointerstitial disease is not known. In this article, we demonstrate that in more than half of a cohort of 68 lupus nephritis biopsies, the tubulointerstitial infiltrate was organized into well-circumscribed T:B cell aggregates or germinal centers (GCs) containing follicular dendritic cells. Sampling of the in situ-expressed Ig repertoire revealed that both histological patterns were associated with intrarenal B cell clonal expansion and ongoing somatic hypermutation. However, in the GC histology, the proliferating cells were CD138(-)CD20(+) centroblasts, whereas they were CD138(+)CD20(low/-) plasmablasts in T:B aggregates. The presence of GCs or T:B aggregates was strongly associated with tubular basement membrane immune complexes. These data implicate tertiary lymphoid neogenesis in the pathogenesis of lupus tubulointerstitial inflammation.
Asunto(s)
Subgrupos de Linfocitos B/inmunología , Subgrupos de Linfocitos B/patología , Túbulos Renales/inmunología , Túbulos Renales/patología , Nefritis Lúpica/inmunología , Nefritis Lúpica/patología , Inmunidad Adaptativa , Adolescente , Adulto , Secuencia de Aminoácidos , Secuencia de Bases , Movimiento Celular/genética , Movimiento Celular/inmunología , Niño , Preescolar , Células Clonales , Células Dendríticas Foliculares/inmunología , Células Dendríticas Foliculares/patología , Femenino , Centro Germinal/inmunología , Centro Germinal/patología , Humanos , Lactante , Inflamación/genética , Inflamación/inmunología , Inflamación/patología , Nefritis Lúpica/genética , Masculino , Datos de Secuencia Molecular , Células Plasmáticas/inmunología , Células Plasmáticas/patología , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/patología , Adulto JovenRESUMEN
Cerebral cavernous malformations (CCMs) represent clusters of dilated vascular channels, predisposing to hemorrhagic stroke and seizures. They are associated with defective blood brain barrier, hemorrhages of different ages and a robust inflammatory cell infiltrate. We report for the first time evidence of co-localized IgG and complement membrane attack complexes in CCM lesions. CD4(+) and CD8(+) T-cells are aggregated with CD20(+) B-cells. And IgG repertoire analyses demonstrate in situ B-cell clonal expansion and antigen-driven affinity maturation in CCMs. These results suggest an organ-intrinsic adaptive immune response in CCMs that should be further characterized as a potential therapeutic target.