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Erschienen in: Journal of Clinical Immunology 1/2007

01.01.2007

Solute Carrier Family 11 Member A1 Gene Polymorphisms in Reactive Arthritis

verfasst von: YI-JING CHEN, CHIA-HUI LIN, TSAN-TENG OU, CHENG-CHIN WU, WEN-CHAN TSAI, HONG-WEN LIU, JENG-HSIEN YEN

Erschienen in: Journal of Clinical Immunology | Ausgabe 1/2007

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Abstract

To investigate the role of SLC 11A1 polymorphisms in the development of reactive arthritis, 91 patients with reactive arthritis and 163 healthy controls were enrolled in this study. The SLC 11A1 polymorphisms were determined by the method of polymerase chain reaction/restriction fragment length polymorphism. The genotype distributions of SLC 11A1 274, 823, 1703, and 1729+ 55 del 4 were significantly different between the patients with reactive arthritis and controls. The genotype frequency of SLC 11A1 274C/C was significantly decreased in the patients with reactive arthritis when compared with that of the controls. In contrast, the SLC 11A1 274C/T showed a significant association with reactive arthritis. The patients with reactive arthritis have a significantly higher frequency of SLC 11A1 823C/C than the controls. However, SLC 11A1 823T/T was resistant to the development of reactive arthritis. The allele frequencies of SLC 11A1 274T and 823C were significantly increased in the patients with reactive arthritis in comparison with those of the controls, independent of HLA-B27. On the contrary, the allele frequencies of SLC 11A1 274C and 823T were significantly decreased in the patients with reactive arthritis. The estimated haplotype frequency of SLC 11A1 274C 823T 1703G 1729+55del 4 TGTG+ was significantly decreased in the patients with reactive arthritis when compared with that of the controls. In contrast, the estimated haplotype frequency of SLC 11A1 274T 823C 1703G 1729+55 del 4 TGTG+ was significantly increased in the patients with reactive arthritis. This study shows that the SLC 11A1 274T and 823C alleles are associated with susceptibility to reactive arthritis independently of HLA-B27 in Taiwan. The SLC 11A1 274T 823C 1703G 1729+55 del 4 TGTG+ haplotype is associated with the development of reactive arthritis in Taiwan. In contrast, the SLC 11A1 274C 823T 1703G 1729+55 del 4 TGTG+ haplotype may be a protective factor.
Literatur
1.
Zurück zum Zitat Khan MA, van der Linden SJ: Reactive arthritis. In Arthritis and Allied Conditions, Vol 1. WJ Koopman, ML Tremblay (eds). Philadelphia, Lippincott Williams & Wilkins, 2005, pp 1335–1355 Khan MA, van der Linden SJ: Reactive arthritis. In Arthritis and Allied Conditions, Vol 1. WJ Koopman, ML Tremblay (eds). Philadelphia, Lippincott Williams & Wilkins, 2005, pp 1335–1355
2.
Zurück zum Zitat Flores D, Marquez J, Garza M, Espinoza LR: Reactive arthritis: Newer developments. Rheum Dis Clin North Am 29(1):37–59, vi, 2003 PubMedCrossRef Flores D, Marquez J, Garza M, Espinoza LR: Reactive arthritis: Newer developments. Rheum Dis Clin North Am 29(1):37–59, vi, 2003 PubMedCrossRef
3.
Zurück zum Zitat Kvien TK, Glennas A, Melby K, Granfors K, Andrup O, Karstensen B, Thoen JE: Reactive arthritis: Incidence, triggering agents and clinical presentation. J Rheumatol 21(1):115–122, 1994 PubMed Kvien TK, Glennas A, Melby K, Granfors K, Andrup O, Karstensen B, Thoen JE: Reactive arthritis: Incidence, triggering agents and clinical presentation. J Rheumatol 21(1):115–122, 1994 PubMed
4.
Zurück zum Zitat Linssen A: B27+ disease versus B27− disease. Scand J Rheumatol 87(Suppl):111–118; discussion 118–119, 1990 Linssen A: B27+ disease versus B27− disease. Scand J Rheumatol 87(Suppl):111–118; discussion 118–119, 1990
5.
Zurück zum Zitat Moller P: Seronegative arthritis—etiology and diagnosis. Scand J Rheumatol 66(Suppl):119–127, 1987 Moller P: Seronegative arthritis—etiology and diagnosis. Scand J Rheumatol 66(Suppl):119–127, 1987
6.
Zurück zum Zitat Yu D, Kuipers JG: Role of bacteria and HLA-B27 in the pathogenesis of reactive arthritis. Rheum Dis Clin North Am 29(1):21–36, v–vi, 2003 PubMedCrossRef Yu D, Kuipers JG: Role of bacteria and HLA-B27 in the pathogenesis of reactive arthritis. Rheum Dis Clin North Am 29(1):21–36, v–vi, 2003 PubMedCrossRef
7.
Zurück zum Zitat Tuokko J, Koskinen S, Westman P, Yli-Kerttula U, Toivanen A, Ilonen J: Tumour necrosis factor microsatellites in reactive arthritis. Br J Rheumatol 37(11):1203–1206, 1998 PubMedCrossRef Tuokko J, Koskinen S, Westman P, Yli-Kerttula U, Toivanen A, Ilonen J: Tumour necrosis factor microsatellites in reactive arthritis. Br J Rheumatol 37(11):1203–1206, 1998 PubMedCrossRef
8.
Zurück zum Zitat Yen JH, Tsai WC, Lin CH, Ou TT, Hu CJ, Liu HW: Cytochrome P450 1A1 and manganese superoxide dismutase genes polymorphisms in reactive arthritis. Immunol Lett 90(2–3):151–154, 2003 PubMedCrossRef Yen JH, Tsai WC, Lin CH, Ou TT, Hu CJ, Liu HW: Cytochrome P450 1A1 and manganese superoxide dismutase genes polymorphisms in reactive arthritis. Immunol Lett 90(2–3):151–154, 2003 PubMedCrossRef
9.
Zurück zum Zitat Blackwell JM, Goswami T, Evans CA, Sibthorpe D, Papo N, White JK, Searle S, Miller EN, Peacock CS, Mohammed H, Ibrahim M: SLC11A1 (formerly NRAMP1) and disease resistance. Cell Microbiol 3(12):773–784, 2001 PubMedCrossRef Blackwell JM, Goswami T, Evans CA, Sibthorpe D, Papo N, White JK, Searle S, Miller EN, Peacock CS, Mohammed H, Ibrahim M: SLC11A1 (formerly NRAMP1) and disease resistance. Cell Microbiol 3(12):773–784, 2001 PubMedCrossRef
10.
Zurück zum Zitat Kingsley G, Sieper J: Third International Workshop on Reactive Arthritis. 23–26 September 1995, Berlin, Germany. Report and abstracts. Ann Rheum Dis 55(8):564–584, 1996 PubMed Kingsley G, Sieper J: Third International Workshop on Reactive Arthritis. 23–26 September 1995, Berlin, Germany. Report and abstracts. Ann Rheum Dis 55(8):564–584, 1996 PubMed
11.
Zurück zum Zitat Haldane JB: The estimation and significance of the logarithm of a ratio of frequencies. Ann Hum Genet 20(4):309–311, 1956 PubMed Haldane JB: The estimation and significance of the logarithm of a ratio of frequencies. Ann Hum Genet 20(4):309–311, 1956 PubMed
12.
Zurück zum Zitat Blackwell JM: Structure and function of the natural-resistance-associated macrophage protein (Nramp1), a candidate protein for infectious and autoimmune disease susceptibility. Mol Med Today 2(5):205–211, 1996 PubMedCrossRef Blackwell JM: Structure and function of the natural-resistance-associated macrophage protein (Nramp1), a candidate protein for infectious and autoimmune disease susceptibility. Mol Med Today 2(5):205–211, 1996 PubMedCrossRef
13.
Zurück zum Zitat Blackwell JM, Barton CH, White JK, Roach TI, Shaw MA, Whitehead SH, Mock BA, Searle S, Williams H, Baker AM: Genetic regulation of leishmanial and mycobacterial infections: The Lsh/Ity/ Bcg gene story continues. Immunol Lett 43(1–2):99–107, 1994 PubMedCrossRef Blackwell JM, Barton CH, White JK, Roach TI, Shaw MA, Whitehead SH, Mock BA, Searle S, Williams H, Baker AM: Genetic regulation of leishmanial and mycobacterial infections: The Lsh/Ity/ Bcg gene story continues. Immunol Lett 43(1–2):99–107, 1994 PubMedCrossRef
14.
Zurück zum Zitat Blackwell JM, Roach TI, Atkinson SE, Ajioka JW, Barton CH, Shaw MA: Genetic regulation of macrophage priming/activation: The Lsh gene story. Immunol Lett 30(2):241–248, 1991 PubMedCrossRef Blackwell JM, Roach TI, Atkinson SE, Ajioka JW, Barton CH, Shaw MA: Genetic regulation of macrophage priming/activation: The Lsh gene story. Immunol Lett 30(2):241–248, 1991 PubMedCrossRef
15.
Zurück zum Zitat Karupiah G, Hunt NH, King NJ, Chaudhri G: NADPH oxidase, Nramp1 and nitric oxide synthase 2 in the host antimicrobial response. Rev Immunogenet 2(3):387–415, 2000 PubMed Karupiah G, Hunt NH, King NJ, Chaudhri G: NADPH oxidase, Nramp1 and nitric oxide synthase 2 in the host antimicrobial response. Rev Immunogenet 2(3):387–415, 2000 PubMed
16.
Zurück zum Zitat Yen JH, Lin CH, Tsai WC, Ou TT, Wu CC, Hu CJ, Liu HW: Natural resistance-associated macrophage protein 1 gene polymorphisms in rheumatoid arthritis. Immunol Lett 102(1):91–97, 2006 Yen JH, Lin CH, Tsai WC, Ou TT, Wu CC, Hu CJ, Liu HW: Natural resistance-associated macrophage protein 1 gene polymorphisms in rheumatoid arthritis. Immunol Lett 102(1):91–97, 2006
17.
Zurück zum Zitat Canonne-Hergaux F, Calafat J, Richer E, Cellier M, Grinstein S, Borregaard N, Gros P: Expression and subcellular localization of NRAMP1 in human neutrophil granules. Blood 100(1):268–275, 2002 PubMedCrossRef Canonne-Hergaux F, Calafat J, Richer E, Cellier M, Grinstein S, Borregaard N, Gros P: Expression and subcellular localization of NRAMP1 in human neutrophil granules. Blood 100(1):268–275, 2002 PubMedCrossRef
18.
Zurück zum Zitat Blackwell JM, Searle S: Genetic regulation of macrophage activation: Understanding the function of Nramp1 (=Ity/Lsh/Bcg). Immunol Lett 65(1–2):73–80, 1999 PubMedCrossRef Blackwell JM, Searle S: Genetic regulation of macrophage activation: Understanding the function of Nramp1 (=Ity/Lsh/Bcg). Immunol Lett 65(1–2):73–80, 1999 PubMedCrossRef
19.
Zurück zum Zitat Forbes JR, Gros P: Iron, manganese, and cobalt transport by Nramp1 (Slc11a1) and Nramp2 (Slc11a2) expressed at the plasma membrane. Blood 102(5):1884–1892, 2003 PubMedCrossRef Forbes JR, Gros P: Iron, manganese, and cobalt transport by Nramp1 (Slc11a1) and Nramp2 (Slc11a2) expressed at the plasma membrane. Blood 102(5):1884–1892, 2003 PubMedCrossRef
20.
Zurück zum Zitat Wyllie S, Seu P, Goss JA: The natural resistance-associated macrophage protein 1 Slc11a1 (formerly Nramp1) and iron metabolism in macrophages. Microbes Infect 4(3):351–359, 2002 PubMedCrossRef Wyllie S, Seu P, Goss JA: The natural resistance-associated macrophage protein 1 Slc11a1 (formerly Nramp1) and iron metabolism in macrophages. Microbes Infect 4(3):351–359, 2002 PubMedCrossRef
21.
Zurück zum Zitat Jabado N, Jankowski A, Dougaparsad S, Picard V, Grinstein S, Gros P: Natural resistance to intracellular infections: Natural resistance-associated macrophage protein 1 (Nramp1) functions as a pH-dependent manganese transporter at the phagosomal membrane. J Exp Med 192(9):1237–1248, 2000 PubMedCrossRef Jabado N, Jankowski A, Dougaparsad S, Picard V, Grinstein S, Gros P: Natural resistance to intracellular infections: Natural resistance-associated macrophage protein 1 (Nramp1) functions as a pH-dependent manganese transporter at the phagosomal membrane. J Exp Med 192(9):1237–1248, 2000 PubMedCrossRef
22.
Zurück zum Zitat Roach TI, Kiderlen AF, Blackwell JM: Role of inorganic nitrogen oxides and tumor necrosis factor alpha in killing Leishmania donovani amastigotes in gamma interferon-lipopolysaccharide-activated macrophages from Lshs and Lshr congenic mouse strains. Infect Immun 59(11):3935–3944, 1991 PubMed Roach TI, Kiderlen AF, Blackwell JM: Role of inorganic nitrogen oxides and tumor necrosis factor alpha in killing Leishmania donovani amastigotes in gamma interferon-lipopolysaccharide-activated macrophages from Lshs and Lshr congenic mouse strains. Infect Immun 59(11):3935–3944, 1991 PubMed
23.
Zurück zum Zitat Arias M, Rojas M, Zabaleta J, Rodriguez JI, Paris SC, Barrera LF, Garcia LF: Inhibition of virulent Mycobacterium tuberculosis by Bcg(r) and Bcg(s) macrophages correlates with nitric oxide production. J Infect Dis 176(6):1552–1558, 1997 PubMedCrossRef Arias M, Rojas M, Zabaleta J, Rodriguez JI, Paris SC, Barrera LF, Garcia LF: Inhibition of virulent Mycobacterium tuberculosis by Bcg(r) and Bcg(s) macrophages correlates with nitric oxide production. J Infect Dis 176(6):1552–1558, 1997 PubMedCrossRef
24.
Zurück zum Zitat Hackam DJ, Rotstein OD, Zhang W, Gruenheid S, Gros P, Grinstein S: Host resistance to intracellular infection: Mutation of natural resistance-associated macrophage protein 1 (Nramp1) impairs phagosomal acidification. J Exp Med 188(2):351–364, 1998 PubMedCrossRef Hackam DJ, Rotstein OD, Zhang W, Gruenheid S, Gros P, Grinstein S: Host resistance to intracellular infection: Mutation of natural resistance-associated macrophage protein 1 (Nramp1) impairs phagosomal acidification. J Exp Med 188(2):351–364, 1998 PubMedCrossRef
25.
Zurück zum Zitat Vidal S, Tremblay ML, Govoni G, Gauthier S, Sebastiani G, Malo D, Skamene E, Olivier M, Jothy S, Gros P: The Ity/Lsh/Bcg locus: Natural resistance to infection with intracellular parasites is abrogated by disruption of the Nramp1 gene. J Exp Med 182(3):655–666, 1995 PubMedCrossRef Vidal S, Tremblay ML, Govoni G, Gauthier S, Sebastiani G, Malo D, Skamene E, Olivier M, Jothy S, Gros P: The Ity/Lsh/Bcg locus: Natural resistance to infection with intracellular parasites is abrogated by disruption of the Nramp1 gene. J Exp Med 182(3):655–666, 1995 PubMedCrossRef
26.
Zurück zum Zitat Blackwell JM, Searle S, Mohamed H, White JK: Divalent cation transport and susceptibility to infectious and autoimmune disease: Continuation of the Ity/Lsh/Bcg/Nramp1/Slc11a1 gene story. Immunol Lett 85(2):197–203, 2003 PubMedCrossRef Blackwell JM, Searle S, Mohamed H, White JK: Divalent cation transport and susceptibility to infectious and autoimmune disease: Continuation of the Ity/Lsh/Bcg/Nramp1/Slc11a1 gene story. Immunol Lett 85(2):197–203, 2003 PubMedCrossRef
27.
Zurück zum Zitat Abe T, Iinuma Y, Ando M, Yokoyama T, Yamamoto T, Nakashima K, Takagi N, Baba H, Hasegawa Y, Shimokata K: NRAMP1 polymorphisms, susceptibility and clinical features of tuberculosis. J Infect 46(4):215–220, 2003 PubMedCrossRef Abe T, Iinuma Y, Ando M, Yokoyama T, Yamamoto T, Nakashima K, Takagi N, Baba H, Hasegawa Y, Shimokata K: NRAMP1 polymorphisms, susceptibility and clinical features of tuberculosis. J Infect 46(4):215–220, 2003 PubMedCrossRef
28.
Zurück zum Zitat Shaw MA, Collins A, Peacock CS, Miller EN, Black GF, Sibthorpe D, Lins-Lainson Z, Shaw JJ, Ramos F, Silveira F, Blackwell JM: Evidence that genetic susceptibility to Mycobacterium tuberculosis in a Brazilian population is under oligogenic control: Linkage study of the candidate genes NRAMP1 and TNFA. Tuberc Lung Dis 78(1):35–45, 1997 CrossRef Shaw MA, Collins A, Peacock CS, Miller EN, Black GF, Sibthorpe D, Lins-Lainson Z, Shaw JJ, Ramos F, Silveira F, Blackwell JM: Evidence that genetic susceptibility to Mycobacterium tuberculosis in a Brazilian population is under oligogenic control: Linkage study of the candidate genes NRAMP1 and TNFA. Tuberc Lung Dis 78(1):35–45, 1997 CrossRef
29.
Zurück zum Zitat Abel L, Sanchez FO, Oberti J, Thuc NV, Hoa LV, Lap VD, Skamene E, Lagrange PH, Schurr E: Susceptibility to leprosy is linked to the human NRAMP1 gene. J Infect Dis 177(1):133–145, 1998 PubMedCrossRef Abel L, Sanchez FO, Oberti J, Thuc NV, Hoa LV, Lap VD, Skamene E, Lagrange PH, Schurr E: Susceptibility to leprosy is linked to the human NRAMP1 gene. J Infect Dis 177(1):133–145, 1998 PubMedCrossRef
30.
Zurück zum Zitat Bellamy R: Susceptibility to mycobacterial infections: The importance of host genetics. Genes Immun 4(1):4–11, 2003 PubMedCrossRef Bellamy R: Susceptibility to mycobacterial infections: The importance of host genetics. Genes Immun 4(1):4–11, 2003 PubMedCrossRef
31.
Zurück zum Zitat Delgado JC, Baena A, Thim S, Goldfeld AE: Ethnic-specific genetic associations with pulmonary tuberculosis. J Infect Dis 186(10):1463–1468, 2002 PubMedCrossRef Delgado JC, Baena A, Thim S, Goldfeld AE: Ethnic-specific genetic associations with pulmonary tuberculosis. J Infect Dis 186(10):1463–1468, 2002 PubMedCrossRef
32.
Zurück zum Zitat Jendro MC, Raum E, Schnarr S, Kohler L, Zeidler H, Kuipers JG, Martin M: Cytokine profile in serum and synovial fluid of arthritis patients with Chlamydia trachomatis infection. Rheumatol Int 25(1):37–41, 2005 PubMedCrossRef Jendro MC, Raum E, Schnarr S, Kohler L, Zeidler H, Kuipers JG, Martin M: Cytokine profile in serum and synovial fluid of arthritis patients with Chlamydia trachomatis infection. Rheumatol Int 25(1):37–41, 2005 PubMedCrossRef
33.
Zurück zum Zitat Smit JJ, Folkerts G, Nijkamp FP: Ramp-ing up allergies: Nramp1 (Slc11a1), macrophages and the hygiene hypothesis. Trends Immunol 25(7):342–347, 2004 PubMedCrossRef Smit JJ, Folkerts G, Nijkamp FP: Ramp-ing up allergies: Nramp1 (Slc11a1), macrophages and the hygiene hypothesis. Trends Immunol 25(7):342–347, 2004 PubMedCrossRef
34.
Zurück zum Zitat Sanjeevi CB, Miller EN, Dabadghao P, Rumba I, Shtauvere A, Denisova A, Clayton D, Blackwell JM: Polymorphism at NRAMP1 and D2S1471 loci associated with juvenile rheumatoid arthritis. Arthritis Rheum 43(6):1397–1404, 2000 PubMedCrossRef Sanjeevi CB, Miller EN, Dabadghao P, Rumba I, Shtauvere A, Denisova A, Clayton D, Blackwell JM: Polymorphism at NRAMP1 and D2S1471 loci associated with juvenile rheumatoid arthritis. Arthritis Rheum 43(6):1397–1404, 2000 PubMedCrossRef
35.
Zurück zum Zitat Bassuny WM, Ihara K, Matsuura N, Ahmed S, Kohno H, Kuromaru R, Miyako K, Hara T: Association study of the NRAMP1 gene promoter polymorphism and early-onset type 1 diabetes. Immunogenetics 54(4):282–285, 2002 PubMedCrossRef Bassuny WM, Ihara K, Matsuura N, Ahmed S, Kohno H, Kuromaru R, Miyako K, Hara T: Association study of the NRAMP1 gene promoter polymorphism and early-onset type 1 diabetes. Immunogenetics 54(4):282–285, 2002 PubMedCrossRef
36.
Zurück zum Zitat Hofmeister A, Neibergs HL, Pokorny RM, Galandiuk S: The natural resistance-associated macrophage protein gene is associated with Crohn’s disease. Surgery 122(2):173–178; discussion 178–179, 1997 PubMedCrossRef Hofmeister A, Neibergs HL, Pokorny RM, Galandiuk S: The natural resistance-associated macrophage protein gene is associated with Crohn’s disease. Surgery 122(2):173–178; discussion 178–179, 1997 PubMedCrossRef
37.
Zurück zum Zitat Kotze MJ, de Villiers JN, Rooney RN, Grobbelaar JJ, Mansvelt EP, Bouwens CS, Carr J, Stander I, du Plessis L: Analysis of the NRAMP1 gene implicated in iron transport: Association with multiple sclerosis and age effects. Blood Cells Mol Dis 27(1):44–53, 2001 PubMedCrossRef Kotze MJ, de Villiers JN, Rooney RN, Grobbelaar JJ, Mansvelt EP, Bouwens CS, Carr J, Stander I, du Plessis L: Analysis of the NRAMP1 gene implicated in iron transport: Association with multiple sclerosis and age effects. Blood Cells Mol Dis 27(1):44–53, 2001 PubMedCrossRef
38.
Zurück zum Zitat Takahashi K, Satoh J, Kojima Y, Negoro K, Hirai M, Hinokio Y, Kinouchi Y, Suzuki S, Matsuura N, Shimosegawa T, Oka Y: Promoter polymorphism of SLC11A1 (formerly NRAMP1) confers susceptibility to autoimmune type 1 diabetes mellitus in Japanese. Tissue Antigens 63(3):231–236, 2004 PubMedCrossRef Takahashi K, Satoh J, Kojima Y, Negoro K, Hirai M, Hinokio Y, Kinouchi Y, Suzuki S, Matsuura N, Shimosegawa T, Oka Y: Promoter polymorphism of SLC11A1 (formerly NRAMP1) confers susceptibility to autoimmune type 1 diabetes mellitus in Japanese. Tissue Antigens 63(3):231–236, 2004 PubMedCrossRef
39.
Zurück zum Zitat Runstadler JA, Saila H, Savolainen A, Leirisalo-Repo M, Aho K, Tuomilehto-Wolf E, Tuomilehto J, Seldin MF: Association of SLC11A1 (NRAMP1) with persistent oligoarticular and polyarticular rheumatoid factor-negative juvenile idiopathic arthritis in Finnish patients: Haplotype analysis in Finnish families. Arthritis Rheum 52(1):247–256, 2005 PubMedCrossRef Runstadler JA, Saila H, Savolainen A, Leirisalo-Repo M, Aho K, Tuomilehto-Wolf E, Tuomilehto J, Seldin MF: Association of SLC11A1 (NRAMP1) with persistent oligoarticular and polyarticular rheumatoid factor-negative juvenile idiopathic arthritis in Finnish patients: Haplotype analysis in Finnish families. Arthritis Rheum 52(1):247–256, 2005 PubMedCrossRef
Metadaten
Titel
Solute Carrier Family 11 Member A1 Gene Polymorphisms in Reactive Arthritis
verfasst von
YI-JING CHEN
CHIA-HUI LIN
TSAN-TENG OU
CHENG-CHIN WU
WEN-CHAN TSAI
HONG-WEN LIU
JENG-HSIEN YEN
Publikationsdatum
01.01.2007
Erschienen in
Journal of Clinical Immunology / Ausgabe 1/2007
Print ISSN: 0271-9142
Elektronische ISSN: 1573-2592
DOI
https://doi.org/10.1007/s10875-006-9050-2

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