PMID- 21244337
OWN - NLM
STAT- MEDLINE
DCOM- 20111028
LR  - 20211020
IS  - 1607-842X (Electronic)
IS  - 0891-6934 (Linking)
VI  - 44
IP  - 5
DP  - 2011 Aug
TI  - The three ZNT8 autoantibody variants together improve the diagnostic sensitivity 
      of childhood and adolescent type 1 diabetes.
PG  - 394-405
LID - 10.3109/08916934.2010.540604 [doi]
AB  - AIMS: We tested whether autoantibodies to all three ZnT8RWQ variants, GAD65, 
      insulinoma-associated protein 2 (IA-2), insulin and autoantibodies to islet cell 
      cytoplasm (ICA) in combination with human leukocyte antigen (HLA) would improve 
      the diagnostic sensitivity of childhood type 1 diabetes by detecting the children 
      who otherwise would have been autoantibody-negative. METHODS: A total of 686 
      patients diagnosed in 1996-2005 in Skane were analyzed for all the seven 
      autoantibodies [arginin 325 zinc transporter 8 autoantibody (ZnT8RA), tryptophan 
      325 zinc transporter 8 autoantibody (ZnT8WA), glutamine 325 Zinc transporter 8 
      autoantibody (ZnT8QA), autoantibodies to glutamic acid decarboxylase (GADA), 
      Autoantibodies to islet-antigen-2 (IA-2A), insulin autoantibodies (IAA) and ICA] 
      in addition to HLA-DQ genotypes. RESULTS: Zinc transporter 8 autoantibody to 
      either one or all three amino acid variants at position 325 (ZnT8RWQA) was found 
      in 65% (449/686) of the patients. The frequency was independent of age at 
      diagnosis. The ZnT8RWQA reduced the frequency of autoantibody-negative patients 
      from 7.5 to 5.4%-a reduction by 28%. Only 2 of 108 (2%) patients who are below 5 
      years of age had no autoantibody at diagnosis. Diagnosis without any islet 
      autoantibody increased with increasing age at onset. DQA1-B1(*)X-0604 was 
      associated with both ZnT8RA (p = 0.002) and ZnT8WA (p = 0.01) but not with ZnT8QA 
      (p = 0.07). Kappa agreement analysis showed moderate (>0.40) to fair (>0.20) 
      agreement between pairs of autoantibodies for all combinations of GADA, IA-2A, 
      ZnT8RWQA and ICA but only slight ( < 0.19) agreement for any combination with 
      IAA. CONCLUSIONS: This study revealed that (1) the ZnT8RWQA was common, 
      independent of age; (2) multiple autoantibodies were common among the young; (3) 
      DQA1-B1(*)X-0604 increased the risk for ZnT8RA and ZnT8WA; (4) agreement between 
      autoantibody pairs was common for all combinations except IAA. These results 
      suggest that ZnT8RWQA is a necessary complement to the classification and 
      prediction of childhood type 1 diabetes as well as to randomize the subjects in 
      the prevention and intervention of clinical trials.
FAU - Andersson, C
AU  - Andersson C
AD  - Department of Clinical Sciences, Skane University Hospital SUS, Lund University, 
      CRC , Malmo , Sweden.
FAU - Larsson, K
AU  - Larsson K
FAU - Vaziri-Sani, F
AU  - Vaziri-Sani F
FAU - Lynch, K
AU  - Lynch K
FAU - Carlsson, A
AU  - Carlsson A
FAU - Cedervall, E
AU  - Cedervall E
FAU - Jonsson, B
AU  - Jonsson B
FAU - Neiderud, J
AU  - Neiderud J
FAU - Mansson, M
AU  - Mansson M
FAU - Nilsson, A
AU  - Nilsson A
FAU - Lernmark, A
AU  - Lernmark A
FAU - Elding Larsson, H
AU  - Elding Larsson H
FAU - Ivarsson, S-A
AU  - Ivarsson SA
LA  - eng
GR  - R01 DK026190/DK/NIDDK NIH HHS/United States
GR  - DK26190/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20110119
PL  - England
TA  - Autoimmunity
JT  - Autoimmunity
JID - 8900070
RN  - 0 (Autoantibodies)
RN  - 0 (Autoantigens)
RN  - 0 (Cation Transport Proteins)
RN  - 0 (HLA-DQ Antigens)
RN  - 0 (ICA1 protein, human)
RN  - 0 (SLC30A8 protein, human)
RN  - 0 (Zinc Transporter 8)
SB  - IM
MH  - Adolescent
MH  - Age Factors
MH  - Autoantibodies/*genetics/*immunology
MH  - Autoantigens/immunology
MH  - Cation Transport Proteins/*genetics/*immunology
MH  - Child
MH  - Child, Preschool
MH  - Diabetes Mellitus, Type 1/*diagnosis/genetics/*immunology
MH  - Female
MH  - Genetic Variation/*genetics
MH  - Genotype
MH  - HLA-DQ Antigens/genetics/immunology
MH  - Humans
MH  - Infant
MH  - Islets of Langerhans/immunology
MH  - Male
MH  - Sensitivity and Specificity
MH  - Sex Factors
MH  - Zinc Transporter 8
EDAT- 2011/01/20 06:00
MHDA- 2011/10/29 06:00
CRDT- 2011/01/20 06:00
PHST- 2011/01/20 06:00 [entrez]
PHST- 2011/01/20 06:00 [pubmed]
PHST- 2011/10/29 06:00 [medline]
AID - 10.3109/08916934.2010.540604 [doi]
PST - ppublish
SO  - Autoimmunity. 2011 Aug;44(5):394-405. doi: 10.3109/08916934.2010.540604. Epub 
      2011 Jan 19.