title: Serum Leukocyte Immunoglobulin-Like Receptor A3 (LILRA3) Is Increased in Patients with Multiple Sclerosis and Is a Strong Independent Indicator of Disease Severity; 6.7kbp LILRA3 Gene Deletion Is Not Associated with Diseases Susceptibility.
abstract: Leukocyte immunoglobulin-like receptor A3 (LILRA3) is a soluble immune regulatory molecule primarily expressed by monocytes and macrophages. A homozygous 6.7kbp LILRA3 gene deletion that removes the first seven of its eight exons is predicted to lead to lack of LILRA3 protein, although this has not been experimentally confirmed. Moreover, there are conflicting results with regards to the link between the LILRA3 homozygous genetic deletion and susceptibility to multiple sclerosis (MS) in different European populations. The aim of this study was to investigate whether LILRA3 gene deletion is associated with MS susceptibility in a North American cohort of European ancestry and assess if serum LILRA3 protein level is a marker of clinical subtype and/or disease severity in MS. A total of 456 patients with MS and 99 unrelated healthy controls were genotyped for the 6.7kbp LILRA3 gene deletion and levels of LILRA3 protein in sera determined by in-house sandwich ELISA. We showed that LILRA3 gene deletion was not associated with MS susceptibility and did not affect the age of disease onset, clinical subtype or disease severity. However, we discovered for the first time that homozygous LILRA3 gene deletion results in lack of production of LILRA3 protein. Importantly, LILRA3 protein level was significantly increased in sera of patients with MS when compared with control subjects, particularly in more severe type primary progressive MS. Multiple regression analysis showed that LILRA3 level in serum was one of the strongest independent markers of disease severity in MS, which potentially can be used as a diagnostic marker.
authors.affiliation: Inflammation and Infection Research Centre, School of Medical Sciences, Department of Pathology, University of New South Wales, Sydney, NSW 2052, Australia.
authors.forename: Hongyan
authors.initials: H
authors.lastname: An
authors.affiliation: MND and Neurodegenerative diseases Research Centre, Australian School of Advanced Medicine (ASAM), Macquarie University, Sydney, NSW 2109, Australia.
authors.forename: Chai
authors.initials: C
authors.lastname: Lim
authors.affiliation: MND and Neurodegenerative diseases Research Centre, Australian School of Advanced Medicine (ASAM), Macquarie University, Sydney, NSW 2109, Australia.
authors.forename: Gilles J
authors.initials: GJ
authors.lastname: Guillemin
authors.affiliation: School of Psychiatry, University of New South Wales, Sydney, NSW 2050, Australia.
authors.forename: Ute
authors.initials: U
authors.lastname: Vollmer-Conna
authors.affiliation: Department of Virology, South Eastern Sydney and Illawarra Health Service, Prince of Wales Hospital, Sydney, NSW 2032, Australia.
authors.forename: William
authors.initials: W
authors.lastname: Rawlinson
authors.affiliation: Inflammation and Infection Research Centre, School of Medical Sciences, Department of Pathology, University of New South Wales, Sydney, NSW 2052, Australia.|South Western Sydney Clinical School, University of New South Wales, Sydney, NSW 2170, Australia.
authors.forename: Katherine
authors.initials: K
authors.lastname: Bryant
authors.affiliation: Inflammation and Infection Research Centre, School of Medical Sciences, Department of Pathology, University of New South Wales, Sydney, NSW 2052, Australia.
authors.forename: Nicodemus
authors.initials: N
authors.lastname: Tedla
mesh_terms: D000328:Adult; D015331:Cohort Studies; D005260:Female; D017353:Gene Deletion; D005787:Gene Frequency; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D009656:North America / Q000453:epidemiology; D011379:Prognosis; D011971:Receptors, Immunologic / Q000097:blood* / Q000235:genetics*; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: C530062:LILRA3 protein, human; D011971:Receptors, Immunologic; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma