Association of Killer Cell Immunoglobulin-like Receptor (KIR) Genes and their HLA Ligands with Susceptibility to Takayasu Arteritis in the Iranian Population
-
Fereshteh Beigmohammadi
,
Saeed Aslani
,
Hoda Kavosi
,
Ali Javinani
,
Shayan Mostafaei
,
Mehran Pournazari
,
Baharak Tasorian
,
Elham Farhadi
,
Asghar Hajiabbasi
,
Habib Zayeni
,
Alireza Khabbazi
,
Ahmadreza Jamshidi
,
Irandokht Shenavar Masooleh
,
Zahra Tamartash
,
Mahdi Vojdanian
,
Mahdi Mahmoudi
Abstract
Takayasu arteritis (TA) is a chronic inflammatory disorder characterized by vascular damage and fibrosis in the intima that commonly occurs in the aorta. In many damaged sites in TA patients, natural killer (NK) cells have been shown to be hyperactivated and produce inflammatory cytokines and toxic components. Killer cell immunoglobulin-like receptors (KIRs) are found on NK cells and interact with human leukocyte antigen (HLA) class I ligands to activate or suppress NK cells. The present study assessed the possible role of KIR and their HLA ligand genes in susceptibility to TA in Iranian patients.
This case-control study included 50 TA patients and 50 healthy subjects. DNA was extracted from whole peripheral blood samples, and polymerase chain reaction with sequence-specific primers (PCR-SSP) was performed to recognize the presence or absence of polymorphism in 17 KIR genes and 5 HLA class I ligands in each participant.
Among the KIR and HLA genes, a significant decrease was detected in the frequency of 2DS4 (full allele) in TA patients (38%) compared with healthy controls (82%) (OR=0.13, 95% CI=0.05–0.34). However, none of the KIR and HLA genotypes or the interactions between these genes were associated with susceptibility to TA.
The KIR2DS4 gene might be involved in the regulation of activation as well as the production of cytotoxic mediators of NK cells in patients with TA.
1. Seyahi E. Takayasu arteritis: an update. Curr Opin Rheumatol. 2017;29(1):51-6.
2. Mason JC. Takayasu arteritis--advances in diagnosis and management. Nat Rev Rheumatol. 2010;6(7):406-15.
3. Zhu WH, Shen LG, Neubauer H. Clinical characteristics, interdisciplinary treatment and follow-up of 14 children with Takayasu arteritis. World J Pediatr. 2010;6(4):342-7.
4. Wen X, Chen S, Li J, Li Y, Li L, Wu Z, et al. Association between genetic variants in the human leukocyte antigen-B/MICA and Takayasu arteritis in Chinese Han population. Int J Rheum Dis. 2018;21(1):271-7.
5. Stojanovic M, Andric Z, Popadic D, Stankovic Stanojevic M, Miskovic R, Jovanovic D, et al. Comprehensive Analysis of the HLA Class I and the HLA Class II Alleles in Patients with Takayasu Arteritis: Relationship with Clinical Patterns and Prognosis. Iran J Immunol. 2021;18(4):354-65.
6. Vargas-Alarcon G, Zuniga J, Gamboa R, Hernandez-Pacheco G, Hesiquio R, Cruz D, et al. DNA sequencing of HLA-B alleles in Mexican patients with Takayasu arteritis. Int J Cardiol. 2000;75( Suppl 1):S117-22.
7. Salazar M, Varela A, Ramirez LA, Uribe O, Vasquez G, Egea E, et al. Association of HLA-DRB1*1602 and DRB1*1001 with Takayasu arteritis in Colombian mestizos as markers of Amerindian ancestry. Int J Cardiol. 2000;(75 Suppl 1):S113-6.
8. Sahin Z, Bicakcigil M, Aksu K, Kamali S, Akar S, Onen F, et al. Takayasu’s arteritis is associated with HLA-B*52, but not with HLA-B*51, in Turkey. Arthritis Res Ther. 2012;14(1):R27.
9. Saruhan-Direskeneli G, Hughes T, Aksu K, Keser G, Coit P, Aydin SZ, et al. Identification of multiple genetic susceptibility loci in Takayasu arteritis. Am J Hum Genet. 2013;93(2):298-305.
10. Stone JR, Bruneval P, Angelini A, Bartoloni G, Basso C, Batoroeva L, et al. Consensus statement on surgical pathology of the aorta from the Society for Cardiovascular Pathology and the Association for European Cardiovascular Pathology: I. Inflammatory diseases. Cardiovasc Pathol. 2015;24(5):267-78.
11. Weyand CM, Goronzy JJ. Medium- and large-vessel vasculitis. N Engl J Med. 2003;349(2):160-9.
12. Seko Y, Sugishita K, Sato O, Takagi A, Tada Y, Matsuo H, et al. Expression of costimulatory molecules (4-1BBL and Fas) and major histocompatibility class I chain-related A (MICA) in aortic tissue with Takayasu’s arteritis. J Vasc Res. 2004;41(1):84-90.
13. Inder SJ, Bobryshev YV, Cherian SM, Lord RS, Masuda K, Yutani C. Accumulation of lymphocytes, dendritic cells, and granulocytes in the aortic wall affected by Takayasu’s disease. Angiology. 2000;51(7):565-79.
14. Trowsdale J, Barten R, Haude A, Stewart CA, Beck S, Wilson MJ. The genomic context of natural killer receptor extended gene families. Immunol Rev. 2001;181:20-38.
15. Jamil KM, Khakoo SI. KIR/HLA interactions and pathogen immunity. J Biomed Biotechnol. 2011;2011:298348.
16. Campbell KS, Purdy AK. Structure/function of human killer cell immunoglobulin-like receptors: lessons from polymorphisms, evolution, crystal structures and mutations. Immunology. 2011;132(3):315-25.
17. Espinoza JL, Ai S, Matsumura I. New Insights on the Pathogenesis of Takayasu Arteritis: Revisiting the Microbial Theory. Pathogens. 2018;7(3).
18. de Souza AW, de Carvalho JF. Diagnostic and classification criteria of Takayasu arteritis. J Autoimmun. 2014;48-49:79-83.
19. Waller R, Ahmed A, Patel I, Luqmani R. Update on the classification of vasculitis. Best Pract Res Clin Rheumatol. 2013;27(1):3-17.
20. Tajik N, Shahsavar F, Mousavi T, Radjabzadeh MF. Distribution of KIR genes in the Iranian population. Tissue Antigens. 2009;74(1):22-31.
21. Tajik N, Shahsavar F, Nasiri M, Radjabzadeh MF. Compound KIR-HLA genotype analyses in the Iranian population by a novel PCR-SSp assay. Int J Immunogenet. 2010;37(3):159-68.
22. Gagne K, Brizard G, Gueglio B, Milpied N, Herry P, Bonneville F, et al. Relevance of KIR gene polymorphisms in bone marrow transplantation outcome. Hum Immunol. 2002;63(4):271-80.
23. Kulkarni S, Martin MP, Carrington M. The Yin and Yang of HLA and KIR in human disease. Semin Immunol. 2008;20(6):343-52.
24. Vilches C, Castaño J, Gómez-Lozano N, Estefanía E. Facilitation of KIR genotyping by a PCR-SSp method that amplifies short DNA fragments. Tissue Antigens. 2007;70(5):415-22.
25. Chainonthee W, Böttcher G, Gagne K, Füssel M, Bignon JD, Wassmuth R. Improved KIR gene and HLA-C KIR ligand sequence-specific primer polymerase chain reaction genotyping using whole genome amplification. Tissue Antigens. 2010;76(2):135-43.
26. Onen F, Akkoc N. Epidemiology of Takayasu arteritis. Presse Med. 2017;46(7-8 Pt 2):e197-e203.
27. Terao C. Revisited HLA and non-HLA genetics of Takayasu arteritis--where are we? J Hum Genet. 2016;61(1):27-32.
28. Mirault T, Guillet H, Messas E. Presse Med. 2017;46(7-8 Pt 2):e189-e96.
29. Ferfar Y, Mirault T, Desbois AC, Comarmond C, Messas E, Savey L, et al. Biotherapies in large vessel vasculitis. Autoimmun Rev. 2016;15(6):544-51.
30. Mekinian A, Comarmond C, Resche-Rigon M, Mirault T, Kahn JE, Lambert M, et al. Efficacy of Biological-Targeted Treatments in Takayasu Arteritis: Multicenter, Retrospective Study of 49 Patients. Circulation. 2015;132(18):1693-700.
31. Williams AP, Bateman AR, Khakoo SI. Hanging in the balance. KIR and their role in disease. Mol Interv. 2005;5(4):226-40.
32. Mahmoudi M, Fallahian F, Sobhani S, Ghoroghi S, Jamshidi A, Poursani S, et al. Analysis of killer cell immunoglobulin-like receptors (KIRs) and their HLA ligand genes polymorphisms in Iranian patients with systemic sclerosis. Clin Rheumatol. 2017;36(4):853-62.
33. 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.
34. Mohammad-Ebrahim H, Kamali-Sarvestani E, Mahmoudi M, Beigy M, Karami J, Ahmadzadeh N, et al. Association of killer cell immunoglobulin-like receptor (KIR) genes and their HLA ligands with susceptibility to Behcet’s disease. Scand J Rheumatol. 2018;47(2):155-63.
35. Origuchi T, Fukui S, Umeda M, Nishino A, Nakashima Y, Koga T, et al. The Severity of Takayasu Arteritis Is Associated with the HLA-B52 Allele in Japanese Patients. Tohoku J Exp Med. 2016;239(1):67-72.
36. Renauer P, Sawalha AH. The genetics of Takayasu arteritis. Presse Med. 2017;46(7-8 Pt 2):e179-e87.
37. Chen S, Luan H, Li L, Zeng X, Wang T, Li Y, et al. Relationship of HLA-B*51 and HLA-B*52 alleles and TNF-alpha-308A/G polymorphism with susceptibility to Takayasu arteritis: a meta-analysis. Clin Rheumatol. 2017;36(1):173-81.
38. Takamura C, Ohhigashi H, Ebana Y, Isobe M. New human leukocyte antigen risk allele in Japanese patients with Takayasu arteritis. Circ J. 2012;76(7):1697-702.
39. Gonzalez-Galarza FF, Takeshita LY, Santos EJ, Kempson F, Maia MH, da Silva AL, et al. Allele frequency net 2015 update: new features for HLA epitopes, KIR and disease and HLA adverse drug reaction associations. Nucleic Acids Res. 2015;43(Database issue):D784-8.
40. Danda D, Goel R, Danda S, Mohan H, Joseph G, Kabeerdoss J, et al. Interleukin-17F and interleukin-6 gene polymorphisms in Asian Indian patients with Takayasu arteritis. Hum Immunol. 2017;78(7-8):515-20.
41. Wen X, Chen S, Li P, Li J, Wu Z, Li Y, et al. Single nucleotide polymorphisms of IL12B are associated with Takayasu arteritis in Chinese Han population. Rheumatol Int. 2017;37(4):547-55.
42. Seko Y, Minota S, Kawasaki A, Shinkai Y, Maeda K, Yagita H, et al. Perforin-secreting killer cell infiltration and expression of a 65-kD heat-shock protein in aortic tissue of patients with Takayasu’s arteritis. J Clin Invest. 1994;93(2):750-8.
43. Espinoza JL, Nguyen VH, Ichimura H, Pham TT, Nguyen CH, Pham TV, et al. A functional polymorphism in the NKG2D gene modulates NK-cell cytotoxicity and is associated with susceptibility to Human Papilloma Virus-related cancers. Sci Rep. 2016;6:39231.
44. Guerra N, Pestal K, Juarez T, Beck J, Tkach K, Wang L, et al. A selective role of NKG2D in inflammatory and autoimmune diseases. Clin Immunol. 2013;149(3):432-9.
45. Espinoza JL, Minami M. Sensing Bacterial-Induced DNA Damaging Effects via Natural Killer Group 2 Member D Immune Receptor: From Dysbiosis to Autoimmunity and Carcinogenesis. Front Immunol. 2018;9:52.
2. Mason JC. Takayasu arteritis--advances in diagnosis and management. Nat Rev Rheumatol. 2010;6(7):406-15.
3. Zhu WH, Shen LG, Neubauer H. Clinical characteristics, interdisciplinary treatment and follow-up of 14 children with Takayasu arteritis. World J Pediatr. 2010;6(4):342-7.
4. Wen X, Chen S, Li J, Li Y, Li L, Wu Z, et al. Association between genetic variants in the human leukocyte antigen-B/MICA and Takayasu arteritis in Chinese Han population. Int J Rheum Dis. 2018;21(1):271-7.
5. Stojanovic M, Andric Z, Popadic D, Stankovic Stanojevic M, Miskovic R, Jovanovic D, et al. Comprehensive Analysis of the HLA Class I and the HLA Class II Alleles in Patients with Takayasu Arteritis: Relationship with Clinical Patterns and Prognosis. Iran J Immunol. 2021;18(4):354-65.
6. Vargas-Alarcon G, Zuniga J, Gamboa R, Hernandez-Pacheco G, Hesiquio R, Cruz D, et al. DNA sequencing of HLA-B alleles in Mexican patients with Takayasu arteritis. Int J Cardiol. 2000;75( Suppl 1):S117-22.
7. Salazar M, Varela A, Ramirez LA, Uribe O, Vasquez G, Egea E, et al. Association of HLA-DRB1*1602 and DRB1*1001 with Takayasu arteritis in Colombian mestizos as markers of Amerindian ancestry. Int J Cardiol. 2000;(75 Suppl 1):S113-6.
8. Sahin Z, Bicakcigil M, Aksu K, Kamali S, Akar S, Onen F, et al. Takayasu’s arteritis is associated with HLA-B*52, but not with HLA-B*51, in Turkey. Arthritis Res Ther. 2012;14(1):R27.
9. Saruhan-Direskeneli G, Hughes T, Aksu K, Keser G, Coit P, Aydin SZ, et al. Identification of multiple genetic susceptibility loci in Takayasu arteritis. Am J Hum Genet. 2013;93(2):298-305.
10. Stone JR, Bruneval P, Angelini A, Bartoloni G, Basso C, Batoroeva L, et al. Consensus statement on surgical pathology of the aorta from the Society for Cardiovascular Pathology and the Association for European Cardiovascular Pathology: I. Inflammatory diseases. Cardiovasc Pathol. 2015;24(5):267-78.
11. Weyand CM, Goronzy JJ. Medium- and large-vessel vasculitis. N Engl J Med. 2003;349(2):160-9.
12. Seko Y, Sugishita K, Sato O, Takagi A, Tada Y, Matsuo H, et al. Expression of costimulatory molecules (4-1BBL and Fas) and major histocompatibility class I chain-related A (MICA) in aortic tissue with Takayasu’s arteritis. J Vasc Res. 2004;41(1):84-90.
13. Inder SJ, Bobryshev YV, Cherian SM, Lord RS, Masuda K, Yutani C. Accumulation of lymphocytes, dendritic cells, and granulocytes in the aortic wall affected by Takayasu’s disease. Angiology. 2000;51(7):565-79.
14. Trowsdale J, Barten R, Haude A, Stewart CA, Beck S, Wilson MJ. The genomic context of natural killer receptor extended gene families. Immunol Rev. 2001;181:20-38.
15. Jamil KM, Khakoo SI. KIR/HLA interactions and pathogen immunity. J Biomed Biotechnol. 2011;2011:298348.
16. Campbell KS, Purdy AK. Structure/function of human killer cell immunoglobulin-like receptors: lessons from polymorphisms, evolution, crystal structures and mutations. Immunology. 2011;132(3):315-25.
17. Espinoza JL, Ai S, Matsumura I. New Insights on the Pathogenesis of Takayasu Arteritis: Revisiting the Microbial Theory. Pathogens. 2018;7(3).
18. de Souza AW, de Carvalho JF. Diagnostic and classification criteria of Takayasu arteritis. J Autoimmun. 2014;48-49:79-83.
19. Waller R, Ahmed A, Patel I, Luqmani R. Update on the classification of vasculitis. Best Pract Res Clin Rheumatol. 2013;27(1):3-17.
20. Tajik N, Shahsavar F, Mousavi T, Radjabzadeh MF. Distribution of KIR genes in the Iranian population. Tissue Antigens. 2009;74(1):22-31.
21. Tajik N, Shahsavar F, Nasiri M, Radjabzadeh MF. Compound KIR-HLA genotype analyses in the Iranian population by a novel PCR-SSp assay. Int J Immunogenet. 2010;37(3):159-68.
22. Gagne K, Brizard G, Gueglio B, Milpied N, Herry P, Bonneville F, et al. Relevance of KIR gene polymorphisms in bone marrow transplantation outcome. Hum Immunol. 2002;63(4):271-80.
23. Kulkarni S, Martin MP, Carrington M. The Yin and Yang of HLA and KIR in human disease. Semin Immunol. 2008;20(6):343-52.
24. Vilches C, Castaño J, Gómez-Lozano N, Estefanía E. Facilitation of KIR genotyping by a PCR-SSp method that amplifies short DNA fragments. Tissue Antigens. 2007;70(5):415-22.
25. Chainonthee W, Böttcher G, Gagne K, Füssel M, Bignon JD, Wassmuth R. Improved KIR gene and HLA-C KIR ligand sequence-specific primer polymerase chain reaction genotyping using whole genome amplification. Tissue Antigens. 2010;76(2):135-43.
26. Onen F, Akkoc N. Epidemiology of Takayasu arteritis. Presse Med. 2017;46(7-8 Pt 2):e197-e203.
27. Terao C. Revisited HLA and non-HLA genetics of Takayasu arteritis--where are we? J Hum Genet. 2016;61(1):27-32.
28. Mirault T, Guillet H, Messas E. Presse Med. 2017;46(7-8 Pt 2):e189-e96.
29. Ferfar Y, Mirault T, Desbois AC, Comarmond C, Messas E, Savey L, et al. Biotherapies in large vessel vasculitis. Autoimmun Rev. 2016;15(6):544-51.
30. Mekinian A, Comarmond C, Resche-Rigon M, Mirault T, Kahn JE, Lambert M, et al. Efficacy of Biological-Targeted Treatments in Takayasu Arteritis: Multicenter, Retrospective Study of 49 Patients. Circulation. 2015;132(18):1693-700.
31. Williams AP, Bateman AR, Khakoo SI. Hanging in the balance. KIR and their role in disease. Mol Interv. 2005;5(4):226-40.
32. Mahmoudi M, Fallahian F, Sobhani S, Ghoroghi S, Jamshidi A, Poursani S, et al. Analysis of killer cell immunoglobulin-like receptors (KIRs) and their HLA ligand genes polymorphisms in Iranian patients with systemic sclerosis. Clin Rheumatol. 2017;36(4):853-62.
33. 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.
34. Mohammad-Ebrahim H, Kamali-Sarvestani E, Mahmoudi M, Beigy M, Karami J, Ahmadzadeh N, et al. Association of killer cell immunoglobulin-like receptor (KIR) genes and their HLA ligands with susceptibility to Behcet’s disease. Scand J Rheumatol. 2018;47(2):155-63.
35. Origuchi T, Fukui S, Umeda M, Nishino A, Nakashima Y, Koga T, et al. The Severity of Takayasu Arteritis Is Associated with the HLA-B52 Allele in Japanese Patients. Tohoku J Exp Med. 2016;239(1):67-72.
36. Renauer P, Sawalha AH. The genetics of Takayasu arteritis. Presse Med. 2017;46(7-8 Pt 2):e179-e87.
37. Chen S, Luan H, Li L, Zeng X, Wang T, Li Y, et al. Relationship of HLA-B*51 and HLA-B*52 alleles and TNF-alpha-308A/G polymorphism with susceptibility to Takayasu arteritis: a meta-analysis. Clin Rheumatol. 2017;36(1):173-81.
38. Takamura C, Ohhigashi H, Ebana Y, Isobe M. New human leukocyte antigen risk allele in Japanese patients with Takayasu arteritis. Circ J. 2012;76(7):1697-702.
39. Gonzalez-Galarza FF, Takeshita LY, Santos EJ, Kempson F, Maia MH, da Silva AL, et al. Allele frequency net 2015 update: new features for HLA epitopes, KIR and disease and HLA adverse drug reaction associations. Nucleic Acids Res. 2015;43(Database issue):D784-8.
40. Danda D, Goel R, Danda S, Mohan H, Joseph G, Kabeerdoss J, et al. Interleukin-17F and interleukin-6 gene polymorphisms in Asian Indian patients with Takayasu arteritis. Hum Immunol. 2017;78(7-8):515-20.
41. Wen X, Chen S, Li P, Li J, Wu Z, Li Y, et al. Single nucleotide polymorphisms of IL12B are associated with Takayasu arteritis in Chinese Han population. Rheumatol Int. 2017;37(4):547-55.
42. Seko Y, Minota S, Kawasaki A, Shinkai Y, Maeda K, Yagita H, et al. Perforin-secreting killer cell infiltration and expression of a 65-kD heat-shock protein in aortic tissue of patients with Takayasu’s arteritis. J Clin Invest. 1994;93(2):750-8.
43. Espinoza JL, Nguyen VH, Ichimura H, Pham TT, Nguyen CH, Pham TV, et al. A functional polymorphism in the NKG2D gene modulates NK-cell cytotoxicity and is associated with susceptibility to Human Papilloma Virus-related cancers. Sci Rep. 2016;6:39231.
44. Guerra N, Pestal K, Juarez T, Beck J, Tkach K, Wang L, et al. A selective role of NKG2D in inflammatory and autoimmune diseases. Clin Immunol. 2013;149(3):432-9.
45. Espinoza JL, Minami M. Sensing Bacterial-Induced DNA Damaging Effects via Natural Killer Group 2 Member D Immune Receptor: From Dysbiosis to Autoimmunity and Carcinogenesis. Front Immunol. 2018;9:52.
| Files | ||
| Issue | Vol 22 No 1 (2023) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijaai.v22i1.12003 | |
| Keywords | ||
| Genetic association Killer cell immunoglobulin-like receptor Natural killer cell Takayasu arteritis | ||
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How to Cite
1.
Beigmohammadi F, Aslani S, Kavosi H, JavinaniA, Mostafaei, Pournazari M, Tasorian B, Farhadi E, Hajiabbasi A, Zayeni H, Khabbazi A, Jamshidi A, Shenavar Masooleh I, Tamartash Z, Vojdanian M, Mahmoudi M. Association of Killer Cell Immunoglobulin-like Receptor (KIR) Genes and their HLA Ligands with Susceptibility to Takayasu Arteritis in the Iranian Population. Iran J Allergy Asthma Immunol. 2023;22(1):25-33.
