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Ansari-Moghaddam B, Kiani A A, Sheikhian A, Birjandi M, Ahmadi S A Y, Mousavi N, et al . Rheumatoid arthritis is associated with KIR2DS4-full among the KIR genes in Lur Population of Iran. rbmb.net. 2021; 10 (1) :84-94
URL: http://rbmb.net/article-1-610-en.html
Department of Immunology, Lorestan University of Medical Sciences, Khorramabad, Iran.
Abstract:   (820 Views)
Background: The pathophysiology underlying the progression and development of autoimmune conditions, such as Rheumatoid Arthritis (RA), is a result of dysregulations of the immune system. Research has explored the genetic alterations present in RA; however, limited studies have examined the role of Killer cell Immunoglobulin-like Receptors (KIR) and Human Leukocyte Antigen (HLA) molecules in RA. Therefore, the aim of this study was to examine KIR genes, their HLA ligands, and KIR-HLA compounds in patients with RA.

Methods: In this case-control study, a total of 50 patients with RA and 100 healthy individuals were enrolled. DNA samples were evaluated using PCR with sequence specific Primers (PCR-SSP). Odds ratio (OR) with a 95% confidence interval (CI) were reported.

Results: Among the KIR genes examined, KIR2DLA (p= 0.0255, OR= 0.389, 95% CI= 0.210-0.722) and KIR2DS4-full (p< 0.0001, OR= 6.163, 95% CI= 3.174-11.968) were observed to have a statistically significant correlation with disease susceptibility to RA. As an inhibitory gene, KIR2DLA was observed to have a protective effect against RA while KIR2DS4-full as an activating gene, was found to increase risk for RA. No significant associations were found between any of the other KIR genotypes, HLA ligands, or KIR-HLA compounds examined in this study to RA susceptibility.

Conclusions: In this study of RA in the Lur population of Iran, KIR2DS4-full was observed to increase susceptibility to RA, while KIR2DL5A was found to act as a protecting factor based on both the cross Table and regression analyses. Further research should focus on repeating this study in additional populations.
Full-Text [PDF 451 kb]   (304 Downloads)    
Type of Article: Original Article | Subject: Immunology
Received: 2020/11/21 | Accepted: 2020/12/13 | Published: 2021/05/9

1. McInnes IB, Schett G. Cytokines in the pathogenesis of rheumatoid arthritis. Nat Rev Immunol. 2007;7(6):429-42. [DOI:10.1038/nri2094] [PMID]
2. Aghaei H, Mostafaei S, Aslani S, Jamshidi A, Mahmoudi M. Association study between KIR polymorphisms and rheumatoid arthritis disease: an updated meta-analysis. BMC Med Genet. 2019;20(1):24. [DOI:10.1186/s12881-019-0754-6] [PMID] [PMCID]
3. Deane KD, Holers VM. The natural history of rheumatoid arthritis. Clin Ther. 2019;41(7):1256-1269. [DOI:10.1016/j.clinthera.2019.04.028] [PMID]
4. Guo Q, Wang Y, Xu D, Nossent J, Pavlos NJ, Xu J. Rheumatoid arthritis: pathological mechanisms and modern pharmacologic therapies. Bone research. 2018;6(1):15. [DOI:10.1038/s41413-018-0016-9] [PMID] [PMCID]
5. Gerlag DM, Raza K, van Baarsen LG, Brouwer E, Buckley CD, Burmester GR, et al. EULAR recommendations for terminology and research in individuals at risk of rheumatoid arthritis: report from the Study Group for Risk Factors for Rheumatoid Arthritis. Ann Rheum Dis. 2012;71(5):638-41. [DOI:10.1136/annrheumdis-2011-200990] [PMID] [PMCID]
6. Abbasi Z, Kazemi Nezhad SR, Pourmahdi-Broojeni M, Rajaei E. Association of PTPN22 rs2476601 Polymorphism with rheumatoid arthritis and celiac disease in Khuzestan province, southwestern Iran. Iran Biomed J. 2017;21(1):61-6. [DOI:10.18869/acadpub.ibj.21.1.61] [PMID] [PMCID]
7. Sánchez-Hernández P, Muñoz-Valle J, Palafox-Sánchez C, Rosales-Rivera L, García-Iglesias T, Daneri-Navarro A, et al. Associations of killer cell immunoglobulin-like receptor genes with rheumatoid arthritis. Dis Markers. 2012;33(4):201-6. [DOI:10.1155/2012/486320] [PMID] [PMCID]
8. Cappelli LC, Dorak MT, Bettinotti MP, Bingham III CO, Shah AA. Association of HLA-DRB1 shared epitope alleles and immune checkpoint inhibitor-induced inflammatory arthritis. Rheumatology. 2018;58(3):476-480. [DOI:10.1093/rheumatology/key358] [PMID] [PMCID]
9. Nazari M, Mahmoudi M, Rahmani F, Akhlaghi M, Beigy M, Azarian M, et al. Association of killer cell immunoglobulin-like receptor genes in iranian patients with rheumatoid arthritis. PloS one. 2015;10(12):e0143757. [DOI:10.1371/journal.pone.0143757] [PMID] [PMCID]
10. Campbell JJ, Qin S, Unutmaz D, Soler D, Murphy KE, Hodge MR, et al. Unique subpopulations of CD56+ NK and NK-T peripheral blood lymphocytes identified by chemokine receptor expression repertoire. J Immunol. 2001;166(11):6477-82. [DOI:10.4049/jimmunol.166.11.6477] [PMID]
11. Fehniger TA, Cooper MA, Nuovo GJ, Cella M, Facchetti F, Colonna M, et al. CD56bright natural killer cells are present in human lymph nodes and are activated by T cell-derived IL-2: a potential new link between adaptive and innate immunity. Blood. 2003;101(8):3052-7. [DOI:10.1182/blood-2002-09-2876] [PMID]
12. Dalbeth N, Callan MF. A subset of natural killer cells is greatly expanded within inflamed joints. Arthritis Rheum. 2002;46(7):1763-72. [DOI:10.1002/art.10410] [PMID]
13. Pende D, Parolini S, Pessino A, Sivori S, Augugliaro R, Morelli L, et al. Identification and molecular characterization of NKp30, a novel triggering receptor involved in natural cytotoxicity mediated by human natural killer cells. J Exp Med. 1999;190(10):1505-16. [DOI:10.1084/jem.190.10.1505] [PMID] [PMCID]
14. Sivori S, Carlomagno S, Pesce S, Moretta A, Vitale M, Marcenaro E. TLR/NCR/KIR: which one to use and when?. Front Immunol. 2014;5:105. [DOI:10.3389/fimmu.2014.00105] [PMID] [PMCID]
15. Lanier LL. On guard-activating NK cell receptors. Nat Immunol. 2001;2(1):23-7. [DOI:10.1038/83130] [PMID]
16. McQueen KL, Parham P. Variable receptors controlling activation and inhibition of NK cells. Curr Opin Immunol. 2002;14(5):615-21. [DOI:10.1016/S0952-7915(02)00380-1]
17. Lanier LL. NK cell receptors. Annual review of immunology. 1998;16(1):359-393. [DOI:10.1146/annurev.immunol.16.1.359] [PMID]
18. Long EO, Barber DF, Burshtyn DN, Faure M, Peterson M, Rajagopalan S, et al. Inhibition of natural killer cell activation signals by killer cell immunoglobulin‐like receptors (CD158). Immunol Rev. 2001;181(1):223-33. [DOI:10.1034/j.1600-065X.2001.1810119.x] [PMID]
19. Moretta A, Bottino C, Vitale M, Pende D, Cantoni C, Mingari MC, et al. Activating receptors and coreceptors involved in human natural killer cell-mediated cytolysis. Annu Rev Immunol. 2001;19(1):197-223. [DOI:10.1146/annurev.immunol.19.1.197] [PMID]
20. Vilches C, Parham P. KIR: diverse, rapidly evolving receptors of innate and adaptive immunity. Annu Rev Immunol. 2002;20:217-51. [DOI:10.1146/annurev.immunol.20.092501.134942] [PMID]
21. Lanier LL. NK cell recognition. Annu Rev Immunol. 2005;23:225-74. [DOI:10.1146/annurev.immunol.23.021704.115526] [PMID]
22. Kumar V, McNerney ME. A new self: MHC-class-I-independent natural-killer-cell self-tolerance. Nat Rev Immunol. 2005;5(5):363-74. [DOI:10.1038/nri1603] [PMID]
23. Carrington M, Norman P. The KIR gene cluster. 2003.
24. Martin AM, Kulski JK, Gaudieri S, Witt CS, Freitas EM, Trowsdale J, et al. Comparative genomic analysis, diversity and evolution of two KIR haplotypes A and B. Gene. 2004;335:121-31. [DOI:10.1016/j.gene.2004.03.018] [PMID]
25. Shilling HG, Guethlein LA, Cheng NW, Gardiner CM, Rodriguez R, Tyan D, et al. Allelic polymorphism synergizes with variable gene content to individualize human KIR genotype. J Immunol. 2002;168(5):2307-15. [DOI:10.4049/jimmunol.168.5.2307] [PMID]
26. Berinstein J, Pollock R, Pellett F, Thavaneswaran A, Chandran V, Gladman DD. Association of variably expressed KIR3dl1 alleles with psoriatic disease. Clin Rheumatol. 2017;36(10):2261-2266. [DOI:10.1007/s10067-017-3784-5] [PMID]
27. Marsh SG, Parham P, Dupont B, Geraghty DE, Trowsdale J, Middleton D, et al. Killer‐cell immunoglobulin‐like receptor (KIR) nomenclature report, 2002. Hum Immunol. 2003;64(6):648-54. [DOI:10.1016/S0198-8859(03)00067-3]
28. Lanier LL, Bakker AB. The ITAM-bearing transmembrane adaptor DAP12 in lymphoid and myeloid cell function. Immunol Today. 2000;21(12):611-4. [DOI:10.1016/S0167-5699(00)01745-X]
29. Rajalingam R. Killer cell immunoglobulin-like receptors influence the innate and adaptive immune responses. Iran J Immunol. 2007;4(2):61-78.
30. Uhrberg M, Valiante NM, Shum BP, Shilling HG, Lienert-Weidenbach K, Corliss B, et al. Human diversity in killer cell inhibitory receptor genes. Immunity. 1997;7(6):753-63. [DOI:10.1016/S1074-7613(00)80394-5]
31. Shahsavar F, Mapar S, Ahmadi SAY. Multiple sclerosis is accompanied by lack of KIR2DS1 gene: A meta-analysis. Genom Data. 2016;10:75-78. [DOI:10.1016/j.gdata.2016.09.009] [PMID] [PMCID]
32. Shahsavar F, Mousavi T, Entezami K, Azargoon A R. Association of KIR-HLA interactions with diseases. Yafteh. 2011;13(3):82-96.
33. Shapouri-Moghaddam A, Mohammadi M, Rahimi HR, Esmaeili H, Mahmoudi M, Modaghegh M-HS, et al. The Association of HLA-A, B and DRB1 with Buerger's Disease. Rep Biochem Mol Biol. 2019;8(2):153-160.
34. Shahsavar F, Varzi A-M, Ahmadi SAY. A genomic study on distribution of human leukocyte antigen (HLA)-A and HLA-B alleles in Lak population of Iran. Genom Data. 2017;11:3-6. [DOI:10.1016/j.gdata.2016.11.012] [PMID] [PMCID]
35. Gonzalez-Galarza FF, McCabe A, Santos EJMd, Jones J, Takeshita L, Ortega-Rivera ND, et al. Allele frequency net database (AFND) 2020 update: gold-standard data classification, open access genotype data and new query tools. Nucleic Acids Res. 2020;48(D1):D783-D788. [DOI:10.1093/nar/gkz1029] [PMID] [PMCID]
36. Shayanrad B, Ghanadi K, Varzi A-M, Birjandi M, Ahmadi SAY, Shahsavar F. Association of KIR genes and their HLA ligands diversity with colorectal cancer in Lur population of Iran. Meta Gene. 2019;22:100603. [DOI:10.1016/j.mgene.2019.100603]
37. Leung W. Infusions of allogeneic natural killer cells as cancer therapy. Clin Cancer Res. 2014;20(13):3390-400. [DOI:10.1158/1078-0432.CCR-13-1766] [PMID]
38. Toubi E, Vadasz Z. Think autoimmunity, breath autoimmunity, and learn autoimmunity. Clin Rheumatol. 2019:38(5):1227-1230. [DOI:10.1007/s10067-019-04540-2] [PMID]
39. Shegarfi H, Naddafi F, Mirshafiey A. Natural killer cells and their role in rheumatoid arthritis: friend or foe?. ScientificWorldJournal. 2012;2012:491974. [DOI:10.1100/2012/491974] [PMID] [PMCID]
40. Yen J-H, Moore BE, Nakajima T, Scholl D, Schaid DJ, Weyand CM, et al. Major histocompatibility complex class I-recognizing receptors are disease risk genes in rheumatoid arthritis. J Exp Med. 2001;193(10):1159-67. [DOI:10.1084/jem.193.10.1159] [PMID] [PMCID]
41. Kogure T, Tatsumi T, Niizawa A, Fujinaga H, Ito T, Shimada Y, et al. No correlation exists between disease activity and the expression of killer-cell immunoglobulin-like receptors in patients with rheumatoid arthritis. Mediators Inflamm. 2007;2007:65179. [DOI:10.1155/2007/65179] [PMID] [PMCID]
42. Yen JH, Lin CH, Tsai WC, Wu CC, Ou TT, Hu CJ, et al. Killer cell immunoglobulin‐like receptor gene's repertoire in rheumatoid arthritis. Scand J Rheumatol. 2006;35(2):124-7. [DOI:10.1080/03009740500381252] [PMID]
43. Li X, Xia Q, Fan D, Cai G, Yang X, Wang L, et al. Association between KIR gene polymorphisms and rheumatoid arthritis susceptibility: a meta-analysis. Human Immunology. 2015;76(8):565-570. [DOI:10.1016/j.humimm.2015.06.017] [PMID]
44. Nishimura WE, Sachetto Z, Costallat LTL, Yazbek MA, Londe ACS, Guariento EG, et al. The role of KIR2DL3/HLA-C* 0802 in Brazilian patients with rheumatoid vasculitis. Clinics. 2015;70(6):408-12. [DOI:10.6061/clinics/2015(06)04]
45. McGeough CM, Berrar D, Wright G, Mathews C, Gilmore P, Cunningham RT, et al. Killer immunoglobulin-like receptor and human leukocyte antigen-C genotypes in rheumatoid arthritis primary responders and non-responders to anti-TNF-α therapy. Rheumatology international. 2012;32(6):1647-53. [DOI:10.1007/s00296-011-1838-6] [PMID] [PMCID]

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