Specific Receptors on Immune Cells May Predict Risk of Aspergillosis Following Allogeneic Stem Cell Transplantation

Researchers from the Fred Hutchinson Cancer Research Center have reported that donor toll-like receptor (TLR) 4 haplotype S4 is associated with an increased risk of invasive aspirgillosis after allogeneic stem cell transplantation. The details of this study appeared in the October 23, issue of the New England Journal of Medicine.

Infections due to aspergillosis are an important cause of morbidity and mortality following allogeneic stem cell transplantation. Incidence rates for invasive aspergillosis in transplant recipients have been reported to be as high as 12%, with a greater than 50% associated mortality. Identification of patients at high risk of developing invasive aspergillosis infection might enable physicians to institute prophylactic measures early, before infection is established. Toll-like receptors (TLRs) are receptors on immune cells that respond to a variety of organisms including aspergillosis species. In other studies, various polymorphisms in TLR genes have been associated with an increased susceptibility to infection.

The current clinical study was performed to determine if there were differences in rates of invasive aspergillosis infection among recipients of donor cells carrying different TLR genes. These researchers evaluated differences, or polymorphisms, in different genes for the TLRs among donors and associated outcomes among patients in regards to the incidence of aspergillosis. The study included 336 patients who had undergone allogeneic stem cell transplantation.

These researchers found that if a patient's unrelated donor had TLR4 haplotypes (S3 and S4), the patient had a 2.5-fold increased risk of developing aspergillosis following the transplant (p=0.02). There was a 2-fold increased incidence of invasive aspergillosis in recipients of related donors with the TLR4 (S3 and S4) haplotype, but this did not reach statistical significance (p=0.07).

There also appeared to be an interaction between donor S4 positivity and cytomegalovirus (CMV) seropositivity. Recipients of donors who were positive for S4 and CMV had a 12% 3-year probability of invasive aspergillosis, compared to 1% for recipients of donors who were S4 negative and CMV seronegative. Recipients of donors who were positive for S4 and CMV had a35% probability of non-leukemic cause of death, compared to 22% for recipients of donors who were S4 negative and CMV seronegative.

These researchers suggested,“The identification of donors who have an increased risk of severe infection may have implications for prevention strategies in recipients of allogeneic hematopoietic-cell transplants.”

Comments: These data may be helpful in identifying high-risk patients for developing invasive aspergillosis infection.

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Reference: Bochud P-Y, Chien J, Marr K, et al. Toll-like Receptor 4 Polymorphisms and Aspergillosis in Stem-Cell Transplantation. New England Journal of Medicine. 2008;359:1766-1777.