Paternal HLA-C and maternal killer-cell immunoglobulin-like receptor genotypes in the development of autism

Moriya Gamliel; Karen L. Anderson; Richard P. Ebstein; Nurit Yirmiya; David Mankuta

doi:10.3389/fped.2016.00076

Paternal HLA-C and maternal killer-cell immunoglobulin-like receptor genotypes in the development of autism

Moriya Gamliel, Karen L. Anderson, Richard P. Ebstein, Nurit Yirmiya, David Mankuta^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

3 Scopus citations

Abstract

Killer-cell immunoglobulin-like receptors (KIRs) are a family of cell surface proteins found on natural killer cells, which are components of the innate immune system. KIRs recognize MHC class I proteins, mainly HLA-C and are further divided into two groups: short-tailed 2/3DS activating receptors and long-tailed 2/3DL inhibitory receptors. Based on the Barker Hypothesis, the origins of illness can be traced back to embryonic development in the uterus, and since KIR:HLA interaction figures prominently in the maternal-fetal interface, we investigated whether specific KIR:HLA combinations may be found in autism spectrum disorders (ASD) children compared with their healthy parents. This study enrolled 49 ASD children from different Israeli families, and their healthy parents. Among the parents, a higher frequency of HLA-C2 allotypes was found in the fathers, while its corresponding ligand 2DS1 was found in higher percentage in the maternal group. However, such skewing in KIR:HLA frequencies did not appear in the ASD children. Additionally, analysis of "overall activation" indicated higher activation in maternal than in paternal cohorts.

Original language	English
Article number	76
Number of pages	8
Journal	Frontiers in Pediatrics
Volume	4
Issue number	JUL
DOIs	https://doi.org/10.3389/fped.2016.00076
State	Published - 1 Jul 2016
Externally published	Yes

Bibliographical note

Funding Information:
This work was supported by a research grant (#232-12-13B) from the National Institute for Psychobiology in Israel, founded by the Charles E. Smith Family, and the Harris Foundation. The authors wish to thank Mrs. Shoshana Israel, Ph.D., and Mrs. Amal Halabi, M.Sc., for their help with validating HLA primers, and Dr. Lubov Nemanov for her assistance in processing patient samples. MG was supported by the Hoffman Leadership and Responsibility Fund, at the Hebrew University.

Publisher Copyright:
© 2016 Gamliel, Anderson, Ebstein, Yirmiya and Mankuta.

Keywords

Autism
HLA
KIR
Natural killer
Pregnancy

Access to Document

10.3389/fped.2016.00076

Cite this

@article{254c09de69674cf4b7d6d55556b892cd,

title = "Paternal HLA-C and maternal killer-cell immunoglobulin-like receptor genotypes in the development of autism",

abstract = "Killer-cell immunoglobulin-like receptors (KIRs) are a family of cell surface proteins found on natural killer cells, which are components of the innate immune system. KIRs recognize MHC class I proteins, mainly HLA-C and are further divided into two groups: short-tailed 2/3DS activating receptors and long-tailed 2/3DL inhibitory receptors. Based on the Barker Hypothesis, the origins of illness can be traced back to embryonic development in the uterus, and since KIR:HLA interaction figures prominently in the maternal-fetal interface, we investigated whether specific KIR:HLA combinations may be found in autism spectrum disorders (ASD) children compared with their healthy parents. This study enrolled 49 ASD children from different Israeli families, and their healthy parents. Among the parents, a higher frequency of HLA-C2 allotypes was found in the fathers, while its corresponding ligand 2DS1 was found in higher percentage in the maternal group. However, such skewing in KIR:HLA frequencies did not appear in the ASD children. Additionally, analysis of {"}overall activation{"} indicated higher activation in maternal than in paternal cohorts.",

keywords = "Autism, HLA, KIR, Natural killer, Pregnancy",

author = "Moriya Gamliel and Anderson, {Karen L.} and Ebstein, {Richard P.} and Nurit Yirmiya and David Mankuta",

note = "Publisher Copyright: {\textcopyright} 2016 Gamliel, Anderson, Ebstein, Yirmiya and Mankuta.",

year = "2016",

month = jul,

day = "1",

doi = "10.3389/fped.2016.00076",

language = "אנגלית",

volume = "4",

journal = "Frontiers in Pediatrics",

issn = "2296-2360",

publisher = "Frontiers Media S.A.",

number = "JUL",

}

TY - JOUR

T1 - Paternal HLA-C and maternal killer-cell immunoglobulin-like receptor genotypes in the development of autism

AU - Gamliel, Moriya

AU - Anderson, Karen L.

AU - Ebstein, Richard P.

AU - Yirmiya, Nurit

AU - Mankuta, David

PY - 2016/7/1

Y1 - 2016/7/1

N2 - Killer-cell immunoglobulin-like receptors (KIRs) are a family of cell surface proteins found on natural killer cells, which are components of the innate immune system. KIRs recognize MHC class I proteins, mainly HLA-C and are further divided into two groups: short-tailed 2/3DS activating receptors and long-tailed 2/3DL inhibitory receptors. Based on the Barker Hypothesis, the origins of illness can be traced back to embryonic development in the uterus, and since KIR:HLA interaction figures prominently in the maternal-fetal interface, we investigated whether specific KIR:HLA combinations may be found in autism spectrum disorders (ASD) children compared with their healthy parents. This study enrolled 49 ASD children from different Israeli families, and their healthy parents. Among the parents, a higher frequency of HLA-C2 allotypes was found in the fathers, while its corresponding ligand 2DS1 was found in higher percentage in the maternal group. However, such skewing in KIR:HLA frequencies did not appear in the ASD children. Additionally, analysis of "overall activation" indicated higher activation in maternal than in paternal cohorts.

AB - Killer-cell immunoglobulin-like receptors (KIRs) are a family of cell surface proteins found on natural killer cells, which are components of the innate immune system. KIRs recognize MHC class I proteins, mainly HLA-C and are further divided into two groups: short-tailed 2/3DS activating receptors and long-tailed 2/3DL inhibitory receptors. Based on the Barker Hypothesis, the origins of illness can be traced back to embryonic development in the uterus, and since KIR:HLA interaction figures prominently in the maternal-fetal interface, we investigated whether specific KIR:HLA combinations may be found in autism spectrum disorders (ASD) children compared with their healthy parents. This study enrolled 49 ASD children from different Israeli families, and their healthy parents. Among the parents, a higher frequency of HLA-C2 allotypes was found in the fathers, while its corresponding ligand 2DS1 was found in higher percentage in the maternal group. However, such skewing in KIR:HLA frequencies did not appear in the ASD children. Additionally, analysis of "overall activation" indicated higher activation in maternal than in paternal cohorts.

KW - Autism

KW - HLA

KW - KIR

KW - Natural killer

KW - Pregnancy

UR - http://www.scopus.com/inward/record.url?scp=85046836671&partnerID=8YFLogxK

U2 - 10.3389/fped.2016.00076

DO - 10.3389/fped.2016.00076

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

AN - SCOPUS:85046836671

SN - 2296-2360

VL - 4

JO - Frontiers in Pediatrics

JF - Frontiers in Pediatrics

IS - JUL

M1 - 76

ER -

Paternal HLA-C and maternal killer-cell immunoglobulin-like receptor genotypes in the development of autism

Abstract

Bibliographical note

Keywords

Access to Document

Other files and links

Fingerprint

Cite this