The Role of HLA-DRB1 Alleles in Pulmonary Cystic Fibrosis
HLA-DR alleles and Pulmonary Cystic Fibrosis
-
Alireza Asef
,
Hossein Ali Ghafaripour
,
Hamidreza Jamaati
,
Mohammad Varahram
,
Ian M. Adcock
,
Esmaeil Mortaz
Abstract
Cystic fibrosis (CF) is the most common lethal autosomal recessive disease in white Caucasians. It affects many organs including the lung, pancreas, and liver. Whilst CF is a monogenic disease, several studies revealed a complex relationship between genotype and clinical phenotype of diseases. We examined the expression of human leukocyte antigen (HLA) class II alleles among Iranian CF patients with disease-related microbial infection.
This study was conducted on 50 hospitalized CF patients (27 males, 23 females aged 15.5±6.5 years), and 50 healthy age- and gender-matched control subjects. 5ml whole blood was harvested and after isolation of genomic DNA, HLA-DRB1 subtypes were determined by single specific primer polymerase chain reaction methods.
HLA-DRB1*10 was less frequent and HLA-DRB1*04 and HLA-DRB1*11 was the most frequent allele in CF patients, but none reached significance. HLA-DRB1*04 allele was frequently seen among16 CF patients with high serum IgE levels (430.25±219.7 IU/mL) and 27 CF patients that were positive for Pseudomonas aeruginosa colonization. A total of 31 CF patients had candida Albicans colonization in whom HLA-DRB1*11 was mostly seen. A total of 3 CF patients had allergic bronchopulmonary aspergillosis and two were diabetic.
The DR4 and DR11 serotypes that recognize the HLA-DRB1*04 and HLA-DRB1*11 gene products respectively are not significantly enriched in the Iranian CF population. Further research should be conducted on DR4 and DR11 in CF patients to understand their possible role in infection and IgE expression.
1. Hofer TP, Frankenberger M, Heimbeck I, Burggraf D, Wjst M, Wright AK, et al. Decreased expression of HLA-DQ and HLA-DR on cells of the monocytic lineage in cystic fibrosis. Journal of molecular medicine. 2014;92(12):1293-304.
2. Nagano Y, Millar BC, Johnson E, Goldsmith CE, Elborn JS, Rendall J, et al. Fungal infections in patients with cystic fibrosis. Reviews in Medical Microbiology. 2007;18(1):11-6.
3. Gallati S. Disease-modifying genes and monogenic disorders: experience in cystic fibrosis. The application of clinical genetics. 2014;7:133.
4. Stern RC. The diagnosis of cystic fibrosis. New England Journal of Medicine. 1997;336(7):487-91.
5. Kerem B-s, Rommens JM, Buchanan JA, Markiewicz D, Cox TK, Chakravarti A, et al. Identification of the cystic fibrosis gene: genetic analysis. Science. 1989;245(4922):1073-80.
6. Tobin M, Maguire O, Reen D, Tempany E, Fitzgerald M. Atopy and bronchial reactivity in older patients with cystic fibrosis. Thorax. 1980;35(11):807-13.
7. Warner JO, Taylor BW, Norman AP, Soothill JF. Association of cystic fibrosis with allergy. Archives of Disease in Childhood. 1976;51(7):507-11.
8. Stenbit A, Flume PA. Pulmonary complications in adult patients with cystic fibrosis. The American journal of the medical sciences. 2008;335(1):55-9.
9. Coutinho HDM, Falcão-Silva VS, Gonçalves FG. Pulmonary bacterial pathogens in cystic fibrosis patients and antibiotic therapy: a tool for the health workers. International archives of medicine. 2008;1(1):1-7.
10. Sabino R, Carolino E, Moss RB, Banaei N, Verissimo C, Stevens DA. Susceptibility of Candida albicans from cystic fibrosis patients. Mycopathologia. 2017;182(9):863-7.
11. Máiz L, Cuevas M, Quirce S, Cañón JF, Pacheco A, Sousa A, et al. Serologic IgE immune responses against Aspergillus fumigatus and Candida albicans in patients with cystic fibrosis. Chest. 2002;121(3):782-8.
12. Shiina T, Hosomichi K, Inoko H, Kulski JK. The HLA genomic loci map: expression, interaction, diversity and disease. Journal of human genetics. 2009;54(1):15-39.
13. Bell J, Smoot S, Newby C, Toyka K, Rassenti L, Smith K, et al. HLA-DQ beta-chain polymorphism linked to myasthenia gravis. The Lancet. 1986;327(8489):1058-60.
14. Gul A, Ohno S. HLA-B* 51 and Behçet disease. Ocular immunology and inflammation. 2012;20(1):37-43.
15. Hill AV, Elvin J, Willis AC, Aidoo M, Allsopp CE, Gotch FM, et al. Molecular analysis of the association of HLA-B53 and resistance to severe malaria. Nature. 1992;360(6403):434-9.
16. Lincoln MR, Montpetit A, Cader MZ, Saarela J, Dyment DA, Tiislar M, et al. A predominant role for the HLA class II region in the association of the MHC region with multiple sclerosis. Nature genetics. 2005;37(10):1108-12.
17. Mack DG, Johnson JJ, Roberts F, Roberts CW, Estes RG, David C, et al. HLA-class II genes modify outcome of Toxoplasma gondii infection. International journal for parasitology. 1999;29(9):1351-8.
18. Petzl-Erler M, Belich M, Queiroz-Telles F. Association of mucosal leishmaniasis with HLA. Human immunology. 1991;32(4):254-60.
19. Zhang Y, Peng Y, Yan H, Xu K, Saito M, Wu H, et al. Multilayered Defense in HLA-B51–Associated HIV Viral Control. The Journal of Immunology. 2011;187(2):684-91.
20. Aron Y, Swierczewski E, Lockhart A. HLA class II haplotype in atopic asthmatic and non‐atopic control subjects. Clinical & Experimental Allergy. 1995;25:65-7.
21. Aron Y, Swierezewski E, Lockhart A. A simple and rapid micromethod for genomic DNA extraction from jugal epithelial cells: application to human lymphocyte antigen typing in one large family of atopic/asthmatic probands. Allergy. 1994;49(9):788-90.
22. Gough SC, Simmonds MJ. The HLA Region and Autoimmune Disease: Associations and Mechanisms of Action. Curr Genomics. 2007;8(7):453-65.
23. Kawa S, Ota M, Yoshizawa K, Horiuchi A, Hamano H, Ochi Y, et al. HLA DRB10405-DQB10401 haplotype is associated with autoimmune pancreatitis in the Japanese population. Gastroenterology. 2002;122(5):1264-9.
24. Fluge G, Olesen H, Gilljam M, Meyer P, Pressler T, Storrösten O, et al. Co-morbidity of cystic fibrosis and celiac disease in Scandinavian cystic fibrosis patients. Journal of Cystic Fibrosis. 2009;8(3):198-202.
25. Walkowiak J, Blask-Osipa A, Lisowska A, Oralewska B, Pogorzelski A, Cichy W, et al. Cystic fibrosis is a risk factor for celiac disease. Acta Biochimica Polonica. 2010;57(1).
26. Wang D, Levasseur‐Acker G, ANKOWSKI R, Kanny G, Moneret‐Vautrin D, Charron D, et al. HLA class II antigens and T lymphocytes in human nasal epithelial cells. Modulation of the HLA class II gene transcripts by gamma interferon. Clinical & Experimental Allergy. 1997;27(3):306-14.
27. Aron Y, Polla BS, Bienvenu T, Dall'ava J, Dusser D, Hubert D. HLA class II polymorphism in cystic fibrosis: a possible modifier of pulmonary phenotype. American journal of respiratory and critical care medicine. 1999;159(5):1464-8.
28. Polverino E, Goeminne PC, McDonnell MJ, Aliberti S, Marshall SE, Loebinger MR, et al. European Respiratory Society guidelines for the management of adult bronchiectasis. European Respiratory Journal. 2017;50(3).
29. Mortaz E, Sereshki HA, Abedini A, Kiani A, Mirsaeidi M, Soroush D, et al. Association of serum TNF-α, IL-8 and free light chain with HLA-DR B alleles expression in pulmonary and extra-pulmonary sarcoidosis. Journal of Inflammation. 2015;12(1):1-8.
30. Adriaanse M, Vreugdenhil A, Groeneweg M, Brüggenwirth H, Castelijns S, van der Ent C, et al. HLA frequencies and associations in cystic fibrosis. Tissue antigens. 2014;83(1):27-31.
31. Hennequet A, Jehanne M, Betuel H, Gilly R, Schmid M, Hors J. Cystic fibrosis and HLA. Tissue antigens. 1978;12(3):159-62.
32. Jones MM, Seilheimer DK, Pollack MS, Curry M, Crane MM, Rossen RD. Relationship of hypergammaglobulinemia, circulating immune complexes, and histocompatibility antigen profiles in patients with cystic fibrosis. The American review of respiratory disease. 1989;140(6):1636-9.
33. Säfwenberg J, Kollberg H, Lindblom J. HLA frequencies in patients with cystic fibrosis. Tissue antigens. 1977;10(4):287-90.
34. Stutchfield P, O'Halloran S, Smith C, Woodrow J, Bottazzo G, Heaf D. HLA type, islet cell antibodies, and glucose intolerance in cystic fibrosis. Archives of disease in childhood. 1988;63(10):1234-9.
35. Turner M, Warner J, Stokes C, Norman A. Immunological studies in cystic fibrosis. Archives of disease in childhood. 1978;53(8):631-8.
36. Witt M, Erickson RP, Ober C, Howatt WF, Farber R. Correlation of phenotypic and genetic heterogeneity in cystic fibrosis: Variability in sweat electrolyte levels contributes to heterogeneity and is increased with the XV‐2c/KM19 B haplotype. American journal of medical genetics. 1991;39(2):137-43.
37. Davies JC. Pseudomonas aeruginosa in cystic fibrosis: pathogenesis and persistence. Paediatric respiratory reviews. 2002;3(2):128-34.
38. Pier GB. Role of the cystic fibrosis transmembrane conductance regulator in innate immunity to Pseudomonas aeruginosa infections. Proceedings of the National Academy of Sciences. 2000;97(16):8822-8.
39. Janahi IA, Rehman A, Al-Naimi AR. Allergic bronchopulmonary aspergillosis in patients with cystic fibrosis. Annals of thoracic medicine. 2017;12(2):74.
40. Roilides E, Uhlig K, Venzon D, Pizzo P, Walsh T. Prevention of corticosteroid-induced suppression of human polymorphonuclear leukocyte-induced damage of Aspergillus fumigatus hyphae by granulocyte colony-stimulating factor and gamma interferon. Infection and Immunity. 1993;61(11):4870-7.
41. Knutsen AP, Bellone C, Kauffman H. Immunopathogenesis of allergic bronchopulmonary aspergillosis in cystic fibrosis. Journal of Cystic Fibrosis. 2002;1(2):76-89.
42. Muro M, Mondejar‐López P, Moya‐Quiles MR, Salgado G, Pastor‐Vivero MD, Lopez‐Hernandez R, et al. HLA‐DRB1 and HLA–DQB1 genes on susceptibility to and protection from allergic bronchopulmonary aspergillosis in patients with cystic fibrosis. Microbiology and immunology. 2013;57(3):193-7.
43. Patterson K, Strek ME. Allergic bronchopulmonary aspergillosis. Proceedings of the American Thoracic Society. 2010;7(3):237-44.
44. Knutsen AP, Chauhan B, Slavin RG. Cell-mediated immunity in allergic bronchopulmonary aspergillosis. Immunology and allergy clinics of North America. 1998;18(3):575-99.
45. Cárdaba B, De Pablo R, Vilches C, Martin E, Geller‐Bernstein C, De Andres B, et al. Allergy to olive pollen: T‐cell response from olive allergic patients is restricted by DR7‐DQ2 antigens. Clinical & Experimental Allergy. 1996;26(3):316-22.
2. Nagano Y, Millar BC, Johnson E, Goldsmith CE, Elborn JS, Rendall J, et al. Fungal infections in patients with cystic fibrosis. Reviews in Medical Microbiology. 2007;18(1):11-6.
3. Gallati S. Disease-modifying genes and monogenic disorders: experience in cystic fibrosis. The application of clinical genetics. 2014;7:133.
4. Stern RC. The diagnosis of cystic fibrosis. New England Journal of Medicine. 1997;336(7):487-91.
5. Kerem B-s, Rommens JM, Buchanan JA, Markiewicz D, Cox TK, Chakravarti A, et al. Identification of the cystic fibrosis gene: genetic analysis. Science. 1989;245(4922):1073-80.
6. Tobin M, Maguire O, Reen D, Tempany E, Fitzgerald M. Atopy and bronchial reactivity in older patients with cystic fibrosis. Thorax. 1980;35(11):807-13.
7. Warner JO, Taylor BW, Norman AP, Soothill JF. Association of cystic fibrosis with allergy. Archives of Disease in Childhood. 1976;51(7):507-11.
8. Stenbit A, Flume PA. Pulmonary complications in adult patients with cystic fibrosis. The American journal of the medical sciences. 2008;335(1):55-9.
9. Coutinho HDM, Falcão-Silva VS, Gonçalves FG. Pulmonary bacterial pathogens in cystic fibrosis patients and antibiotic therapy: a tool for the health workers. International archives of medicine. 2008;1(1):1-7.
10. Sabino R, Carolino E, Moss RB, Banaei N, Verissimo C, Stevens DA. Susceptibility of Candida albicans from cystic fibrosis patients. Mycopathologia. 2017;182(9):863-7.
11. Máiz L, Cuevas M, Quirce S, Cañón JF, Pacheco A, Sousa A, et al. Serologic IgE immune responses against Aspergillus fumigatus and Candida albicans in patients with cystic fibrosis. Chest. 2002;121(3):782-8.
12. Shiina T, Hosomichi K, Inoko H, Kulski JK. The HLA genomic loci map: expression, interaction, diversity and disease. Journal of human genetics. 2009;54(1):15-39.
13. Bell J, Smoot S, Newby C, Toyka K, Rassenti L, Smith K, et al. HLA-DQ beta-chain polymorphism linked to myasthenia gravis. The Lancet. 1986;327(8489):1058-60.
14. Gul A, Ohno S. HLA-B* 51 and Behçet disease. Ocular immunology and inflammation. 2012;20(1):37-43.
15. Hill AV, Elvin J, Willis AC, Aidoo M, Allsopp CE, Gotch FM, et al. Molecular analysis of the association of HLA-B53 and resistance to severe malaria. Nature. 1992;360(6403):434-9.
16. Lincoln MR, Montpetit A, Cader MZ, Saarela J, Dyment DA, Tiislar M, et al. A predominant role for the HLA class II region in the association of the MHC region with multiple sclerosis. Nature genetics. 2005;37(10):1108-12.
17. Mack DG, Johnson JJ, Roberts F, Roberts CW, Estes RG, David C, et al. HLA-class II genes modify outcome of Toxoplasma gondii infection. International journal for parasitology. 1999;29(9):1351-8.
18. Petzl-Erler M, Belich M, Queiroz-Telles F. Association of mucosal leishmaniasis with HLA. Human immunology. 1991;32(4):254-60.
19. Zhang Y, Peng Y, Yan H, Xu K, Saito M, Wu H, et al. Multilayered Defense in HLA-B51–Associated HIV Viral Control. The Journal of Immunology. 2011;187(2):684-91.
20. Aron Y, Swierczewski E, Lockhart A. HLA class II haplotype in atopic asthmatic and non‐atopic control subjects. Clinical & Experimental Allergy. 1995;25:65-7.
21. Aron Y, Swierezewski E, Lockhart A. A simple and rapid micromethod for genomic DNA extraction from jugal epithelial cells: application to human lymphocyte antigen typing in one large family of atopic/asthmatic probands. Allergy. 1994;49(9):788-90.
22. Gough SC, Simmonds MJ. The HLA Region and Autoimmune Disease: Associations and Mechanisms of Action. Curr Genomics. 2007;8(7):453-65.
23. Kawa S, Ota M, Yoshizawa K, Horiuchi A, Hamano H, Ochi Y, et al. HLA DRB10405-DQB10401 haplotype is associated with autoimmune pancreatitis in the Japanese population. Gastroenterology. 2002;122(5):1264-9.
24. Fluge G, Olesen H, Gilljam M, Meyer P, Pressler T, Storrösten O, et al. Co-morbidity of cystic fibrosis and celiac disease in Scandinavian cystic fibrosis patients. Journal of Cystic Fibrosis. 2009;8(3):198-202.
25. Walkowiak J, Blask-Osipa A, Lisowska A, Oralewska B, Pogorzelski A, Cichy W, et al. Cystic fibrosis is a risk factor for celiac disease. Acta Biochimica Polonica. 2010;57(1).
26. Wang D, Levasseur‐Acker G, ANKOWSKI R, Kanny G, Moneret‐Vautrin D, Charron D, et al. HLA class II antigens and T lymphocytes in human nasal epithelial cells. Modulation of the HLA class II gene transcripts by gamma interferon. Clinical & Experimental Allergy. 1997;27(3):306-14.
27. Aron Y, Polla BS, Bienvenu T, Dall'ava J, Dusser D, Hubert D. HLA class II polymorphism in cystic fibrosis: a possible modifier of pulmonary phenotype. American journal of respiratory and critical care medicine. 1999;159(5):1464-8.
28. Polverino E, Goeminne PC, McDonnell MJ, Aliberti S, Marshall SE, Loebinger MR, et al. European Respiratory Society guidelines for the management of adult bronchiectasis. European Respiratory Journal. 2017;50(3).
29. Mortaz E, Sereshki HA, Abedini A, Kiani A, Mirsaeidi M, Soroush D, et al. Association of serum TNF-α, IL-8 and free light chain with HLA-DR B alleles expression in pulmonary and extra-pulmonary sarcoidosis. Journal of Inflammation. 2015;12(1):1-8.
30. Adriaanse M, Vreugdenhil A, Groeneweg M, Brüggenwirth H, Castelijns S, van der Ent C, et al. HLA frequencies and associations in cystic fibrosis. Tissue antigens. 2014;83(1):27-31.
31. Hennequet A, Jehanne M, Betuel H, Gilly R, Schmid M, Hors J. Cystic fibrosis and HLA. Tissue antigens. 1978;12(3):159-62.
32. Jones MM, Seilheimer DK, Pollack MS, Curry M, Crane MM, Rossen RD. Relationship of hypergammaglobulinemia, circulating immune complexes, and histocompatibility antigen profiles in patients with cystic fibrosis. The American review of respiratory disease. 1989;140(6):1636-9.
33. Säfwenberg J, Kollberg H, Lindblom J. HLA frequencies in patients with cystic fibrosis. Tissue antigens. 1977;10(4):287-90.
34. Stutchfield P, O'Halloran S, Smith C, Woodrow J, Bottazzo G, Heaf D. HLA type, islet cell antibodies, and glucose intolerance in cystic fibrosis. Archives of disease in childhood. 1988;63(10):1234-9.
35. Turner M, Warner J, Stokes C, Norman A. Immunological studies in cystic fibrosis. Archives of disease in childhood. 1978;53(8):631-8.
36. Witt M, Erickson RP, Ober C, Howatt WF, Farber R. Correlation of phenotypic and genetic heterogeneity in cystic fibrosis: Variability in sweat electrolyte levels contributes to heterogeneity and is increased with the XV‐2c/KM19 B haplotype. American journal of medical genetics. 1991;39(2):137-43.
37. Davies JC. Pseudomonas aeruginosa in cystic fibrosis: pathogenesis and persistence. Paediatric respiratory reviews. 2002;3(2):128-34.
38. Pier GB. Role of the cystic fibrosis transmembrane conductance regulator in innate immunity to Pseudomonas aeruginosa infections. Proceedings of the National Academy of Sciences. 2000;97(16):8822-8.
39. Janahi IA, Rehman A, Al-Naimi AR. Allergic bronchopulmonary aspergillosis in patients with cystic fibrosis. Annals of thoracic medicine. 2017;12(2):74.
40. Roilides E, Uhlig K, Venzon D, Pizzo P, Walsh T. Prevention of corticosteroid-induced suppression of human polymorphonuclear leukocyte-induced damage of Aspergillus fumigatus hyphae by granulocyte colony-stimulating factor and gamma interferon. Infection and Immunity. 1993;61(11):4870-7.
41. Knutsen AP, Bellone C, Kauffman H. Immunopathogenesis of allergic bronchopulmonary aspergillosis in cystic fibrosis. Journal of Cystic Fibrosis. 2002;1(2):76-89.
42. Muro M, Mondejar‐López P, Moya‐Quiles MR, Salgado G, Pastor‐Vivero MD, Lopez‐Hernandez R, et al. HLA‐DRB1 and HLA–DQB1 genes on susceptibility to and protection from allergic bronchopulmonary aspergillosis in patients with cystic fibrosis. Microbiology and immunology. 2013;57(3):193-7.
43. Patterson K, Strek ME. Allergic bronchopulmonary aspergillosis. Proceedings of the American Thoracic Society. 2010;7(3):237-44.
44. Knutsen AP, Chauhan B, Slavin RG. Cell-mediated immunity in allergic bronchopulmonary aspergillosis. Immunology and allergy clinics of North America. 1998;18(3):575-99.
45. Cárdaba B, De Pablo R, Vilches C, Martin E, Geller‐Bernstein C, De Andres B, et al. Allergy to olive pollen: T‐cell response from olive allergic patients is restricted by DR7‐DQ2 antigens. Clinical & Experimental Allergy. 1996;26(3):316-22.
| Files | ||
| Issue | Vol 21 No 2 (2022) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijaai.v21i2.9226 | |
| Keywords | ||
| Cystic fibrosis HLA-DRB1 chains Pseudomonas aeruginosa Staphylococcus aureus | ||
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How to Cite
1.
Asef A, Ghafaripour HA, Jamaati H, Varahram M, M. Adcock I, Mortaz E. The Role of HLA-DRB1 Alleles in Pulmonary Cystic Fibrosis. Iran J Allergy Asthma Immunol. 2022;21(2):189-196.
