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.
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...
Main Authors: | , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2016-01-01
|
Series: | PLoS ONE |
Online Access: | http://europepmc.org/articles/PMC4752247?pdf=render |
_version_ | 1828191183767076864 |
---|---|
author | Hongyan An Chai Lim Gilles J Guillemin Ute Vollmer-Conna William Rawlinson Katherine Bryant Nicodemus Tedla |
author_facet | Hongyan An Chai Lim Gilles J Guillemin Ute Vollmer-Conna William Rawlinson Katherine Bryant Nicodemus Tedla |
author_sort | Hongyan An |
collection | DOAJ |
description | 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. |
first_indexed | 2024-04-12T08:34:42Z |
format | Article |
id | doaj.art-e8cc9e4249964294a9c6a21de8c3fa17 |
institution | Directory Open Access Journal |
issn | 1932-6203 |
language | English |
last_indexed | 2024-04-12T08:34:42Z |
publishDate | 2016-01-01 |
publisher | Public Library of Science (PLoS) |
record_format | Article |
series | PLoS ONE |
spelling | doaj.art-e8cc9e4249964294a9c6a21de8c3fa172022-12-22T03:40:04ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01112e014920010.1371/journal.pone.0149200Serum 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.Hongyan AnChai LimGilles J GuilleminUte Vollmer-ConnaWilliam RawlinsonKatherine BryantNicodemus TedlaLeukocyte 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.http://europepmc.org/articles/PMC4752247?pdf=render |
spellingShingle | Hongyan An Chai Lim Gilles J Guillemin Ute Vollmer-Conna William Rawlinson Katherine Bryant Nicodemus Tedla 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. PLoS ONE |
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. |
title_full | 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. |
title_fullStr | 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. |
title_full_unstemmed | 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. |
title_short | 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. |
title_sort | 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 |
url | http://europepmc.org/articles/PMC4752247?pdf=render |
work_keys_str_mv | AT hongyanan serumleukocyteimmunoglobulinlikereceptora3lilra3isincreasedinpatientswithmultiplesclerosisandisastrongindependentindicatorofdiseaseseverity67kbplilra3genedeletionisnotassociatedwithdiseasessusceptibility AT chailim serumleukocyteimmunoglobulinlikereceptora3lilra3isincreasedinpatientswithmultiplesclerosisandisastrongindependentindicatorofdiseaseseverity67kbplilra3genedeletionisnotassociatedwithdiseasessusceptibility AT gillesjguillemin serumleukocyteimmunoglobulinlikereceptora3lilra3isincreasedinpatientswithmultiplesclerosisandisastrongindependentindicatorofdiseaseseverity67kbplilra3genedeletionisnotassociatedwithdiseasessusceptibility AT utevollmerconna serumleukocyteimmunoglobulinlikereceptora3lilra3isincreasedinpatientswithmultiplesclerosisandisastrongindependentindicatorofdiseaseseverity67kbplilra3genedeletionisnotassociatedwithdiseasessusceptibility AT williamrawlinson serumleukocyteimmunoglobulinlikereceptora3lilra3isincreasedinpatientswithmultiplesclerosisandisastrongindependentindicatorofdiseaseseverity67kbplilra3genedeletionisnotassociatedwithdiseasessusceptibility AT katherinebryant serumleukocyteimmunoglobulinlikereceptora3lilra3isincreasedinpatientswithmultiplesclerosisandisastrongindependentindicatorofdiseaseseverity67kbplilra3genedeletionisnotassociatedwithdiseasessusceptibility AT nicodemustedla serumleukocyteimmunoglobulinlikereceptora3lilra3isincreasedinpatientswithmultiplesclerosisandisastrongindependentindicatorofdiseaseseverity67kbplilra3genedeletionisnotassociatedwithdiseasessusceptibility |