Fighting infections while dealing with chronic diseases has been a persistent challenge, especially during the Covid-19 pandemic. A recent study by Stony Brook Medicine reveals that advanced kidney disease weakens the survival of B cells, which are crucial for producing antibodies to combat microbes. This impairment significantly diminishes the immune response to influenza.
The research findings have been published in Nature Communications. The study was led by Partha Biswas, a professor at Stony Brook University's Renaissance School of Medicine. Biswas and his team aimed to understand why individuals with kidney disease struggle to mount an effective immune response. They focused on uremia, a condition marked by toxic metabolite accumulation due to impaired kidney filtration.
Kidney disease is linked with increased risk of severe infections and related deaths. Infections rank as the second leading cause of death among kidney disease patients, with about 20 percent succumbing to infections according to the International Society of Nephrology. During the Covid-19 pandemic, mortality rates were up to ten times higher for those with kidney disease compared to those without.
Clinical studies have often reported poor B cell-mediated antibody responses post-infection or vaccination in kidney disease patients. However, reasons for this remain unclear. "Most studies linking kidney disease with abnormal B cell response were either performed in kidney transplant patients or are correlative in nature," said Biswas.
Using a murine model of kidney disease that progresses to renal dysfunction, researchers immunized healthy mice and those with kidney disease with model immunogens or infected them with influenza virus. This triggered a germinal center response in the spleen essential for developing protective antibody levels.
The study revealed several cellular changes explaining the poor immune response observed in the kidney disease model. Biswas noted that their paper provides insights into how kidney disease affects protective B cell responses during infection and immunization.
Biswas and his team plan to use this experimental system to investigate the lack of response to SARS-CoV-2 vaccination in individuals with kidney disease, potentially offering broader implications for other respiratory viruses and bacterial infections affecting these patients.
The research received support from multiple National Institutes of Health grants, including several awarded directly to Dr. Biswas: AI142354, AI162616, AI159058, and AI181831. Collaborators included scientists from various departments at the University of Pittsburgh and the Medical College of Georgia.