Fighting infections while managing chronic diseases can be challenging, particularly during the Covid-19 pandemic when it proved to be both dangerous and deadly. A recent study conducted by Stony Brook Medicine has revealed that advanced kidney disease impairs the survival of B cells, a type of white blood cell responsible for producing antibodies to combat microbes. This impairment significantly weakens the immune response to influenza. The research findings have been published in Nature Communications.
Comorbid health conditions play a crucial role in determining immune function. Kidney disease is one such condition linked with an increased risk of severe infection and related deaths. Infections are reported as the second leading cause of death among kidney disease patients, with approximately 20 percent succumbing to infections according to the International Society of Nephrology. During the Covid-19 pandemic, individuals with kidney disease faced mortality rates up to ten times higher than those with normal kidney function.
The study, led by Partha Biswas, DVM, PhD, a Professor at Stony Brook University's Renaissance School of Medicine, sought to understand why individuals with kidney disease struggle to mount an effective immune response. The focus was on uremia, a condition arising from toxic metabolite accumulation due to impaired kidney filtration.
Clinical studies often indicate a poor B cell-mediated antibody response following infection or vaccination in those suffering from kidney disease. Although kidney disease predisposes individuals to infection complications, the underlying reasons 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 Dr. Biswas. "Since kidney transplant patients are immunocompromised, it is difficult to assess the impact of kidney disease on B cell response per se."
The researchers utilized well-characterized murine models of kidney disease that lead to renal dysfunction. Both healthy mice and those with kidney disease were immunized or infected with influenza virus to initiate a germinal center (GC) response in the spleen—a key process for developing protective antibodies and infection-fighting responses.
Dr. Biswas explained that their paper provides mechanistic insights into how kidney disease adversely affects protective B cell responses during infection and immunization. He believes that these findings may illuminate ways to enhance antibody responses following vaccination in individuals with kidney disease.
Dr. Biswas and his team are currently preparing to use this experimental system to address the apparent lack of response to SARS-CoV-2 vaccination among individuals with kidney disease—a challenge that could have broader implications for other respiratory viruses and bacterial infections affecting these patients.
This research received partial funding through several National Institutes of Health (NIH) grants awarded 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.