Molecule Holds Key in Avoiding Organ Rejection

Researchers at the Medical College of Georgia Center for Molecular Chaperone/Radiobiology and Cancer Virology have found via a rodent study that an immune system molecule called HLA-G dimer may help in avoiding organ rejection.

According to researchers, the molecule's action can be augmented in people with organ transplants and autoimmune disease and turned down to help fight a tumour.

Measuring endogenous levels of HLA-G dimer may also help physicians identify which transplant patients require little, if any, immune suppression.

"This is a molecule with huge potential to regulate immune response," Dr. Anatolij Horuzsko, reproductive immunologist at the Medical College of Georgia Center for Molecular Chaperone/Radiobiology and Cancer Virology.

Researchers have found that dimer appears to be the most powerful among several known forms of HLA-G at inhibiting the immune response.

The study showed that when HLA-G dimer binds with its inhibitory receptor, ILT4, it triggers a signaling pathway in which immune molecules IL-6 and STAT3 play a major role.

"Biologically this is an interaction that requires several important suppressive molecules," said Dr. Horuzsko, co-author and a faculty member in the MCG Schools of Medicine and Graduate Studies.

The researchers looked at the resulting strong signaling in culture, then measured its impact on skin graft survival in mice and found it prolonged survival.

Now, Dr. Horuzsko is working with Dr. Laura Mulloy, chief of the Section of Nephrology, Hypertension and Transplantation Medicine in the MCG School of Medicine, to see if this dimer form is at work in kidney transplant patients who avoid rejection.

HLA-G dimer's target is another MHC molecule, which is essentially an individual's unique tissue signature; HLA-G itself is a type of MHC.

In fact, HLA - human leukocyte antigen - matching is done for organ and bone marrow transplants to try minimize the recipient's reaction to the new organ.

Transplant patients also take drugs that broadly dampen the immune response but can leave them more vulnerable to infections and disease.

Dr. Horuzsko notes that HLA-G can work through other cells, not just MHC molecules, and that not every HLA-G form is good at down-regulating MHC.

He plans to look at HLA-G dimer levels in tumour patients as well.

The study is published online in Proceedings of the National Academy of Sciences.

Source-ANI
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