In antibody-positive first-degree relatives of patients with type 1 diabetes, HLA-A*24 and HLA-B*18, but not HLA-B*39, are predictors of impending diabetes with distin
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- 作者：E. Mbunwe (1)
B. J. Van der Auwera (1)
I. Weets (1) (2)
P. Van Crombrugge (3)
L. Crenier (4)
M. Coeckelberghs (5)
N. Seret (6)
K. Decochez (1) (7)
E. Vandemeulebroucke (1) (7)
P. Gillard (8)
B. Keymeulen (1) (7)
C. van Schravendijk (1)
J. M. Wenzlau (9)
J. C. Hutton (9)
D. G. Pipeleers (1)
F. K. Gorus (1) (2) - 关键词：Autoantibodies ; HLA ; A ; HLA ; B ; HLA class I ; HLA class II ; HLA ; DQ ; Prediction ; Prevention ; Risk assessment ; Type 1 diabetes
- 刊名：Diabetologia
- 出版年：2013
- 出版时间：September 2013
- 年：2013
- 卷：56
- 期：9
- 页码：1964-1970
- 全文大小：187KB
- 参考文献：1. Mbunwe E, van der Auwera BJ, Vermeulen I et al (2013) HLA-A*24 is an independent predictor of 5-year progression to diabetes in autoantibody-positive first-degree relatives of type 1 diabetic patients. Diabetes 62:1345-350 CrossRef
2. von Herrath M, Peakman M, Roep B (2013) Progress in immune-based therapies for type 1 diabetes. Clin Exp Immunol 172:186-02 CrossRef
3. Tait BD, Colman PG, Morahan G et al (2003) HLA genes associated with autoimmunity and progression to disease in type 1 diabetes. Tissue Antigens 61:146-53 CrossRef
4. Lipponen K, Gombos Z, Kiviniemi M et al (2010) Effect of HLA class I and class II alleles on progression from autoantibody positivity to overt type 1 diabetes in children with risk-associated class II genotypes. Diabetes 59:3253-256 CrossRef
5. Nejentsev S, Howson JM, Walker NM et al (2007) Localization of type 1 diabetes susceptibility to the MHC class I genes HLA-B and HLA-A. Nature 450:887-92 CrossRef
6. Fennessy M, Metcalfe K, Hitman GA et al (1994) A gene in the HLA class I region contributes to susceptibility to IDDM in the Finnish population. Diabetologia 37:937-44 CrossRef
7. Valdes AM, Wapelhorst B, Concannon P, Erlich HA, Thomson G, Noble JA (2005) Extended DR3-D6S273-HLA-B haplotypes are associated with increased susceptibility to type 1 diabetes in US Caucasians. Tissue Antigens 65:115-19 CrossRef
8. Vermeulen I, Weets I, Costa O et al (2012) An important minority of prediabetic first-degree relatives of type 1 diabetic patients derives from seroconversion to persistent autoantibody positivity after 10 years of age. Diabetologia 55:413-20 CrossRef
9. The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus (1997) Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 20:1183-197
10. Middleton D (2000) PCR-SSOP class I and class II (DRBI). In: Hahn AB, Land GA, Strothman RM (eds), ASHI laboratory manual, 4th edition. American Society for Histocompatibility and Immunogenetics, Lenexa, p. V.C.2.1-3
11. Greenbaum CJ, Buckingham B, Chase HP, Krischer J (2011) Metabolic tests to determine risk for type 1 diabetes in clinical trials. Diabetes Metab Res Rev 27:584-89 CrossRef
12. Xu P, Beam CA, Cuthbertson D, Sosenko JM, Skyler JS, Krischer JP (2012) Prognostic accuracy of immunologic and metabolic markers for type 1 diabetes in a high-risk population: receiver operating characteristic analysis. Diabetes Care 35:1975-980 CrossRef
13. Honeyman MC, Harrison LC, Drummond B, Colman PG, Tait BD (1995) Analysis of families at risk for insulin-dependent diabetes mellitus reveals that HLA antigens influence progression to clinical disease. Mol Med 1:576-82
14. Valdes AM, Erlich HA, Noble JA (2005) Human leukocyte antigen class I B and C loci contribute to type 1 diabetes (T1D) susceptibility and age at T1D onset. Hum Immunol 66:301-13 CrossRef
15. Kronenberg D, Knight RR, Estorninho M et al (2012) Circulating preproinsulin signal peptide-specific CD8 T cells restricted by the susceptibility molecule HLA-A24 are expanded at onset of type 1 diabetes and kill beta-cells. Diabetes 61:1752-759 CrossRef
16. Marron MP, Graser RT, Chapman HD, Serreze DV (2002) Functional evidence for the mediation of diabetogenic T cell responses by HLA-A2.1 MHC class I molecules through transgenic expression in NOD mice. Proc Natl Acad Sci U S A 99:13753-3758 CrossRef
17. van Belle TL, Coppieters KT, von Herrath MG (2011) Type 1 diabetes: etiology, immunology, and therapeutic strategies. Physiol Rev 91:79-18 CrossRef
18. Vandemeulebroucke E, Keymeulen B, Decochez K et al (2010) Hyperglycaemic clamp test for diabetes risk assessment in IA-2-antibody-positive relatives of type 1 diabetic patients. Diabetologia 53:36-4 CrossRef
19. Long AE, Gillespie KM, Aitken RJ, Goode JC, Bingley PJ, Williams AJ (2013) Humoral responses to islet antigen-2 and zinc transporter 8 are attenuated in patients carrying HLA-A*24 alleles at the onset of type 1 diabetes. Diabetes. doi:10.2337/db12-1468
20. Nakanishi K, Kobayashi T, Murase T, Naruse T, Nose Y, Inoko H (1999) Human leukocyte antigen-A24 and -DQA1*0301 in Japanese insulin-dependent diabetes mellitus: independent contributions to susceptibility to the disease and additive contributions to acceleration of beta-cell destruction. J Clin Endocrinol Metab 84:3721-725 CrossRef - 作者单位：E. Mbunwe (1)
B. J. Van der Auwera (1)
I. Weets (1) (2)
P. Van Crombrugge (3)
L. Crenier (4)
M. Coeckelberghs (5)
N. Seret (6)
K. Decochez (1) (7)
E. Vandemeulebroucke (1) (7)
P. Gillard (8)
B. Keymeulen (1) (7)
C. van Schravendijk (1)
J. M. Wenzlau (9)
J. C. Hutton (9)
D. G. Pipeleers (1)
F. K. Gorus (1) (2)
1. Diabetes Research Center, Brussels Free University-VUB, Laarbeeklaan 103, 1090, Brussels, Belgium
2. Department of Clinical Chemistry and Radio-immunology, University Hospital Brussels Free University-UZ Brussel, Brussels, Belgium
3. Department of Endocrinology, OLV-Ziekenhuis, Aalst, Belgium
4. Department of Endocrinology, ULB-Erasme Hospital, Brussels, Belgium
5. Department of Diabetology, Paola Kinderziekenhuis, Antwerp, Belgium
6. Department of Pediatrics, CHC Clinique Saint-Joseph, Liège, Belgium
7. Department of Diabetology, University Hospital Brussels Free University-UZ Brussel, Brussels, Belgium
8. Department of Clinical and Experimental Medicine, University of Leuven-KUL and University Hospitals, Leuven, Belgium
9. Barbara Davis Center for Childhood Diabetes, University of Colorado at Denver, Aurora, CO, USA
文摘
Aims/hypothesis Secondary type 1 diabetes prevention trials require selection of participants with impending diabetes. HLA-A and -B alleles have been reported to promote disease progression. We investigated whether typing for HLA-B*18 and -B*39 may complement screening for HLA-DQ8, -DQ2 and -A*24 and autoantibodies (Abs) against islet antigen-2 (IA-2) and zinc transporter 8 (ZnT8) for predicting rapid progression to hyperglycaemia. Methods A registry-based group of 288 persistently autoantibody-positive (Ab+) offspring/siblings (aged 0-9?years) of known patients (Ab+ against insulin, GAD, IA-2 and/or ZnT8) were typed for HLA-DQ, -A and -B and monitored from the first Ab+ sample for development of diabetes within 5?years. Results Unlike HLA-B*39, HLA-B*18 was associated with accelerated disease progression, but only in HLA-DQ2 carriers (p-lt;-.006). In contrast, HLA-A*24 promoted progression preferentially in the presence of HLA-DQ8 (p-lt;-.002). In HLA-DQ2- and/or HLA-DQ8-positive relatives (n--46), HLA-B*18 predicted impending diabetes (p--.015) in addition to HLA-A*24, HLA-DQ2/DQ8 and positivity for IA-2A or ZnT8A (p?≤-.004). HLA-B*18 interacted significantly with HLA-DQ2/DQ8 and HLA-A*24 in the presence of IA-2 and/or ZnT8 autoantibodies (p?≤-.009). Additional testing for HLA-B*18 and -A*24 significantly improved screening sensitivity for rapid progressors, from 38% to 53%, among relatives at high Ab-inferred risk carrying at least one genetic risk factor. Screening for HLA-B*18 increased sensitivity for progressors, from 17% to 28%, among individuals carrying ? risk markers conferring >85% 5 year risk. Conclusions/interpretation These results reinforce the importance of HLA class I alleles in disease progression and quantify their added value for preparing prevention trials.