Entropy of human leukocyte antigen and killer-cell immunoglobulin-like receptor systems in immune-mediated disorders: A pilot study on multiple sclerosis

Autoři: Maurizio Melis aff001;  Roberto Littera aff002;  Eleonora Cocco aff003;  Jessica Frau aff003;  Sara Lai aff002;  Elena Congeddu aff001;  Paola Ragatzu aff001;  Maria Serra aff002;  Valentina Loi aff002;  Roberta Maddi aff002;  Roberta Pitzalis aff003;  Sandro Orrù aff001;  Luchino Chessa aff004;  Andrea Perra aff005;  Carlo Carcassi aff001
Působiště autorů: Medical Genetics, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy aff001;  Complex Structure of Medical Genetics, R. Binaghi Hospital, ASSL Cagliari, ATS Sardegna, Italy aff002;  Multiple Sclerosis Center, R. Binaghi Hospital, University of Cagliari/ATS Sardegna, Cagliari, Italy aff003;  Center for the Study of Liver Diseases, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy aff004;  Unit of Oncology and Molecular Pathology, Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy aff005
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
doi: 10.1371/journal.pone.0226615



Entropy is a thermodynamic variable statistically correlated with the disorder of a system. The hypothesis that entropy can be used to identify potentially unhealthy conditions was first suggested by Schrödinger, one of the founding fathers of quantum mechanics. Shannon later defined entropy as the quantity of information stored in a system. Shannon’s entropy has the advantage of being adaptable across a variety of disciplines, including genetic studies on complex immunogenetic systems such as the human leukocyte antigen (HLA) and killer-cell immunoglobulin-like receptor (KIR) systems.


In our study, entropy associated to the HLA and KIR systems was compared between a cohort of 619 Sardinian healthy controls and a group of 270 patients affected by multiple sclerosis (MS), the latter stratified into 81 patients with primary progressive multiple sclerosis (PPMS) and 189 patients with relapsing remitting multiple sclerosis (RRMS).


The entropy associated to HLA four-loci haplotypes (A, B, C, DR) and combinations of two inhibitory KIR genes was significantly higher in patients affected by RRMS than in healthy controls. No significant differences were observed for patients with PPMS. By calculating the total HLA and KIR entropy ratio in each subject, it was possible to determine the individual risk of developing MS, particularly RRMS.


In addition to the standard statistical methods used to evaluate immunogenetic parameters associated to immune-mediated disease, the analysis of entropy measures the global disorder status deriving from these parameters. This innovative approach may represent a useful complementary tool to the risk assessment of immune-mediated disorders. Improved risk assessment is particularly important for family members of patients with MS. However, further investigation is warranted to confirm our findings and to evaluate the validity of the entropy-based method in other types of immune-mediated disorders.

Klíčová slova:

Antigens – Disabilities – Entropy – Genetics of disease – Haplotypes – Immune response – Information entropy – Multiple sclerosis


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