Reduced proportions of natural killer T cells are present in the relatives of lupus patients and are associated with autoimmunity View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2008-10

AUTHORS

Joan Wither, Yong-chun Cai, Sooyeol Lim, Tamara McKenzie, Nicole Roslin, Jaime O Claudio, Glinda S Cooper, Thomas J Hudson, Andrew D Paterson, Celia MT Greenwood, Dafna Gladman, Janet Pope, Christian A Pineau, C Douglas Smith, John G Hanly, Christine Peschken, Gilles Boire, CaNIOS Investigators, Paul R Fortin

ABSTRACT

INTRODUCTION: Systemic lupus erythematosus is a genetically complex disease. Currently, the precise allelic polymorphisms associated with this condition remain largely unidentified. In part this reflects the fact that multiple genes, each having a relatively minor effect, act in concert to produce disease. Given this complexity, analysis of subclinical phenotypes may aid in the identification of susceptibility alleles. Here, we used flow cytometry to investigate whether some of the immune abnormalities that are seen in the peripheral blood lymphocyte population of lupus patients are seen in their first-degree relatives. METHODS: Peripheral blood mononuclear cells were isolated from the subjects, stained with fluorochrome-conjugated monoclonal antibodies to identify various cellular subsets, and analyzed by flow cytometry. RESULTS: We found reduced proportions of natural killer (NK)T cells among 367 first-degree relatives of lupus patients as compared with 102 control individuals. There were also slightly increased proportions of memory B and T cells, suggesting increased chronic low-grade activation of the immune system in first-degree relatives. However, only the deficiency of NKT cells was associated with a positive anti-nuclear antibody test and clinical autoimmune disease in family members. There was a significant association between mean parental, sibling, and proband values for the proportion of NKT cells, suggesting that this is a heritable trait. CONCLUSIONS: The findings suggest that analysis of cellular phenotypes may enhance the ability to detect subclinical lupus and that genetically determined altered immunoregulation by NKT cells predisposes first-degree relatives of lupus patients to the development of autoimmunity. More... »

PAGES

r108

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/ar2505

DOI

http://dx.doi.org/10.1186/ar2505

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1021259881

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/18783591


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435 University of Toronto Lupus Clinic, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network; Department of Medicine, University of Toronto, Bathurst Street, M5T 2S8, Toronto, Ontario, Canada
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438 schema:name Division of Rheumatology, Department of Medicine, Faculty of Medicine, University of Manitoba, Sherbrook Street, R3A 1M4, Winnipeg, Manitoba, Canada
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447 schema:name Division of Rheumatology, St Joseph's Health Centre, Grosvenor Street, N6A 4V2, London, Ontario, Canada
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450 schema:name United States Environmental Protection Agency, Pennsylvania Avenue NW, 20460, Washington, District of Columbia, USA
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452 https://www.grid.ac/institutes/grid.42327.30 schema:alternateName Hospital for Sick Children
453 schema:name Program in Genetics and Genome Biology, The Hospital for Sick Children Research Institute, College Street, M5G 1L7, Toronto, Ontario, Canada
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455 https://www.grid.ac/institutes/grid.55602.34 schema:alternateName Dalhousie University
456 schema:name Division of Rheumatology, Department of Medicine, Queen Elizabeth II Health Sciences Centre and Dalhousie University, Summer Street, B3H 4K4, Halifax, Nova Scotia, Canada
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458 https://www.grid.ac/institutes/grid.63984.30 schema:alternateName McGill University Health Centre
459 schema:name Division of Rheumatology, McGill University Health Center, Cedar Avenue, H3G 1A4, Montreal, Quebec, Canada
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461 https://www.grid.ac/institutes/grid.86715.3d schema:alternateName Université de Sherbrooke
462 schema:name Division of Rheumatology, Department of Medicine, Faculty of Medicine and Health Sciences, Université de Sherbrooke, 12th Avenue N, J1H 5N4, Sherbrooke, Quebec, Canada
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