Antonio Paul/LinkedIn

Jan 20, 2026, 13:08

Antonio Paul on Blame Game in Transplantation: HLA vs Microbes

Antonio Paul, Head of ACTIMoS- Advanced Center for Transplant Immunology and Molecular Science, shared on LinkedIn:

”Blame Game in Transplantation: HLA vs Microbes

What if HLA antibodies are not always about HLA?

For decades, we’ve taught that anti-HLA antibodies arise from the usual suspects:

But many patients develop de novo anti-HLA antibodies without any classic sensitization history.

Growing evidence suggests another culprit: Infections.

What’s happening?

Microbes can trigger HLA antibodies through several mechanisms:

Molecular mimicry – Microbial antigens may resemble HLA epitopes, leading to cross-reactive antibodies.
Innate immune “danger signals” – Toll-like receptor activation can break immune tolerance and promote rejection.
Bystander B-cell activation – Cytokine surges during infection can awaken dormant HLA-reactive memory B cells.
Polyclonal immune activation – Broad antibody expansion may occur after infections or vaccinations.

Clinical evidence shows that infections often precede:

– Increased panel reactive antibodies (PRA)
– Emergence of donor-specific antibodies (DSA)
– Higher rejection risk
– Poorer graft survival

Rethinking an old assumption

Not all HLA antibodies are born from mismatched HLA.

Some may be born from mismatched microbes.

Transplant success may depend not only on how well donors and recipients are matched, but also on which microbes the immune system remembers.”

Antonio Paul on Blame Game in Transplantation: HLA vs Microbes