Antibodies to kidney endothelial cells contribute to a "leaky" glomerular barrier in patients with chronic kidney diseases.

• Anti-endothelial cell antibodies (AECA) are reported to cause endothelial dysfunction but their clinical importance with tissue specific endothelial cells is not clear. We hypothesized that AECA reactive with human kidney endothelial cells (HKEC) may cause renal endothelial dysfunction in patients with chronic kidney diseases. We found that a (p < 0.001) higher fraction of end-stage renal disease patients (ESRD) (56%) have AECA reactive with glomerular endothelial cells as compared to healthy controls (5%). Presence of antibodies was associated with female sex (p < 0.001), systolic hypertension (p < 0.01) and elevated tumour necrosis factor-alpha (TNF-α, p < 0.05). These antibodies markedly decrease expression of adherens and tight junction proteins VE-cadherin, Claudin-1 and ZO-1 and provoked a rapid increase in cytosolic free Ca(2+) and rearrangement of actin filaments in HKEC as compared to controls, followed by an enhancement in protein flux and phosphorylation of VE-cadherin, events associated with augmented endothelial cell permeability. Staining of kidney biopsies from ESRD patients with AECA but not controls demonstrated a marked decrease in adherens and tight junctions in glomerular endothelium, confirming our in vitro data. In summary, our data demonstrate a causal link between AECA and their capacity to induce alterations in glomerular vascular permeability.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine (hsv//eng)

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