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Association of variably expressed KIR3dl1 alleles with psoriatic disease

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Abstract

The purpose of this study is to examine the genetic interaction of variably expressed killer cell immunoglobulin-like receptor (KIR) 3DL1 alleles with their cognate ligand, human leukocyte antigen (HLA)-Bw4, in susceptibility to psoriatic disease (PsD). A novel allelic typing system was developed to differentiate KIR3DL1 alleles (*High, *Low, *Null expression, and 3DS1), in PsD patients, including those with psoriatic arthritis (PsA) and cutaneous psoriasis without arthritis (PsC) and healthy controls. Frequencies of each KIR3DL1 allele, Bw4-80I and Bw4-80T, as well as the genetic interaction between the KIR3DL1 alleles and the Bw4 epitope were analyzed. KIR3DL1 alleles were successfully genotyped in 392 PsA, 260 PsC, and 371 control subjects. Only the KIR3DL1*Null allele was associated with PsD (OR = 0.69, p = 0.008), both in the PsA (OR = 0.69, p = 0.02) and PsC patients (OR = 0.70, p = 0.04) compared to control subjects. No difference in the frequency of KIR3DL1*Null was found between the PsA and PsC patients. The presence of the HLA-Bw4 epitope was significantly associated with PsD, particularly in the PsA patients compared to controls. Bw4-80I was increased in PsD and PsA subjects, but not in PsC patients compared to controls. Bw4-80T was increased in PsA compared to both PsC patients or to controls. No interaction was detected between any of the KIR3DL1 alleles and HLA-Bw4, Bw4-80I, or Bw4-80T. The novel qPCR technique successfully identified the four variably expressed KIR3DL1 alleles. The HLA-Bw4 epitope was associated with psoriatic disease, particularly with PsA, but no genetic interactions with KIR3DL1 alleles were detected.

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Acknowledgments

The PsA clinic is supported by a grant from the Krembil Foundation. Jeffrey Berinstein was supported by the Canadian Institutes of Health Research (CIHR) and Institute of Musculoskeletal Health and Arthritis (IMHA) summer studentship. Remy Pollock was supported by a CIHR Banting and Best Canada Graduate Scholarship Doctoral Research Award.

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Author notes

  1. Jeffrey Berinstein and Remy Pollock contributed equally to this work

Authors and Affiliations

  1. University of Toronto Psoriatic Arthritis Clinic, Centre for Prognosis Studies in the Rheumatic Diseases 1E-410B, Toronto Western Hospital, 399 Bathurst Street, Toronto, ON, M5T 2S8, Canada

    Jeffrey Berinstein, Remy Pollock, Fawnda Pellett, Arane Thavaneswaran, Vinod Chandran & Dafna D. Gladman

  2. Krembil Research Institute, Toronto Western Hospital, Toronto, ON, Canada

    Jeffrey Berinstein, Remy Pollock, Fawnda Pellett, Arane Thavaneswaran, Vinod Chandran & Dafna D. Gladman

  3. Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA

    Jeffrey Berinstein

  4. Department of Medicine, Faculty of Medicine, University of Toronto, Toronto, ON, Canada

    Remy Pollock, Vinod Chandran & Dafna D. Gladman

  5. Institute of Medical Science, University of Toronto, Toronto, ON, Canada

    Vinod Chandran & Dafna D. Gladman

  6. Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, ON, Canada

    Vinod Chandran

Authors
  1. Jeffrey Berinstein
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  2. Remy Pollock
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  3. Fawnda Pellett
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  4. Arane Thavaneswaran
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  5. Vinod Chandran
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  6. Dafna D. Gladman
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Correspondence to Dafna D. Gladman.

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Berinstein, J., Pollock, R., Pellett, F. et al. Association of variably expressed KIR3dl1 alleles with psoriatic disease. Clin Rheumatol 36, 2261–2266 (2017). https://doi.org/10.1007/s10067-017-3784-5

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  • DOI: https://doi.org/10.1007/s10067-017-3784-5

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