Primary renal tubulointerstitial disease resulting from proximal tubule antigen-specific antibodies and immune complex formation has not been well characterized in humans. We report a cohort of patients with a distinct, underappreciated kidney disease characterized by kidney antibrush border antibodies and renal failure (ABBA disease). We identified ten patients with ABBA disease who had a combination of proximal tubule damage, IgG-positive immune deposits in the tubular basement membrane, and circulating antibodies reactive with normal human kidney proximal tubular brush border. All but one of the patients also had segmental glomerular deposits on renal biopsy specimen. Patients with ABBA disease were elderly and presented with AKI and subnephrotic proteinuria. Serum from all patients but not controls recognized a high molecular weight protein in renal tubular protein extracts that we identified as LDL receptor-related protein 2 (LRP2), also known as megalin, by immunoprecipitation and mass spectrometry. Immunostaining revealed that LRP2 specifically colocalized with IgG in the tubular immune deposits on the ABBA biopsy specimen but not the control specimen analyzed. Finally, ABBA serum samples but not control samples showed reactivity against recombinantly expressed N-terminal LRP2 fragments on Western blots and immunoprecipitated the recombinantly expressed N-terminal region of LRP2. This case series details the clinicopathologic findings of patients with ABBA disease and shows that the antigenic target of these autoantibodies is LRP2. Future studies are needed to determine the disease prevalence, stimulus for ABBA, and optimal treatment.
This is the first study in which it is documented that some of the perilesional hypoperfused tissue around human ICH regains its perfusion in the long term, leading the authors to suggest that there may be a penumbra in human ICH. Medical or surgical therapeutic interventions could increase the volume of perilesional brain that recovers after the initial insult. The results of this study therefore support the concept that intervention in ICH has the potential to reduce the ultimate neurological deficit and improve outcome.
On the basis of these data the authors suggest that TICH and SICH have different features: TICH affects a slightly younger age group and carries a much better prognosis compared with SICH. In addition, indications for surgical intervention are not well defined for either type of hemorrhage. Practice is subjective and inconsistent. The International Surgical Trial in Intracerebral Haemorrhage may resolve the dilemma for SICH. A similar trial in which surgery is compared with conservative management should be considered for cases of TICH.
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