Abstract 5819: Long-term Existence of the Autoantibodies Against the Second Extracellular Loop of β1-Adrenoceptor Induces Kidney Injury in Rats
Background: The effects of antibodies against the second extracellular loop (ECII) of β1-adrenoceptors (β1-AA) have been extensive investigated in cardiovascular disease. Our previous study has demonstrated that peritoneal exudate had been induced after long-term active immunization with synthetic peptides corresponding to human β1-AR-ECII in rats. We hypothesis that β1-AA may also bind with β1-AR in kidney and display pathophysiological roles.
Methods: Immunization models were set up using either the peptides corresponding to the ECII of β1-adrenoceptors or β1-AA in Rats; the long-term effects of anti- β1-AR-ECII on kidney structure and function were observed.
Results: Compared with the vehicle group, blood urea nitrogen (BUN), creatinine (CR), and uric acid (UA) increased, and the BUN-to-CR ratio decreased markedly at the 8th week after immunization with peptides (BUN: 8.9±0.95 mM vs 6.7±0.35 mM, P<0.05; CR: 70.0±3.85 mM vs 40.9±1.38 mM, P<0.01; UA: 235.6±16.43 mM vs 89.5±9.80 mM, P<0.01; BUN/CR: 0.11±0.008 vs 0.16±0.008, P<0.01). At the 28th week after immunization, BUN and CR were still higher than those in the vehicle group (P<0.05, P<0.01); BUN/CR was also lower than the vehicle group (P<0.05). HE and Masson’s staining revealed some mononuclear cell infiltration around the renal glomerulus, and collagen fibers accumulation around the renal tubules in 9 rats. To exclude the possible toxic role of antigen peptides to kidney in active immunization, passive immunization model by injection of purified β1-AA was used to confirm the above results. BUN, CR, UA significantly increased, and BUN/CR decreased as comparing with the negative sera group at 24th week after immunization (BUN: 9.25±0.43 mM vs 6.56±0.28 mM; CR: 68.8±8.05 mM vs 41.8±1.39 mM; UA: 166.5±21.14 mM vs 86.3±12.35 mM; BUN/CR: 0.14±0.009 vs 0.16±0.006; all P<0.01). The morphological changes after passive immunization by HE or Masson’s staining is consistent with the results of active immunization.
Conclusion: Anti-β1-AA could lead impairment of kidney function and structure, suggesting that anti-β1-AA may have a broad spectrum of organ injury effect in addition to its reported harmful effects in cardiovascular system.