PMID- 18573919
OWN - NLM
STAT- MEDLINE
DCOM- 20080715
LR  - 20161018
IS  - 1479-683X (Electronic)
IS  - 0804-4643 (Linking)
VI  - 159
IP  - 1
DP  - 2008 Jul
TI  - Characterization of the humoral immune response to islet antigen 2 in children 
      with newly diagnosed type 1 diabetes.
PG  - 19-26
LID - 10.1530/EJE-07-0853 [doi]
AB  - OBJECTIVE: To characterize the humoral immune response to islet antigen 2 (IA-2) 
      in patients with newly diagnosed type 1 diabetes (T1D), we compared the profile 
      of epitope- and isotype-specific IA-2 antibodies (IA-2A) between children with a 
      humoral immune response restricted to IA-2 and children with a broad response 
      including insulin autoantibodies (IAA) and antibodies to glutamic acid 
      decarboxylase (GADA) in addition to IA-2A. METHODS: The study subjects (n=100) 
      were derived from a consecutive series of 1108 patients from the Finnish 
      Pediatric Diabetes Register (investigators listed in the Appendix). Islet cell 
      antibodies, IAA, GADA, total IA-2A levels, IA-2/IA-2beta epitopes, and isotypes 
      were measured, and human leukocyte antigen (HLA) genotypes were analyzed. 
      RESULTS: There were no significant differences between the two groups in the 
      frequency or levels of epitope-specific IA-2A. Those with an IA-2-restrictive 
      response tested positive more frequently for IgA-IA-2A (P=0.001), had higher 
      titers of IgE-IA-2A (P=0.025), tested positive for more IA-2A isotypes than the 
      broad responders (P=0.04), and carried the high-risk HLA-(DR4)-DQB1*0302 
      haplotype more frequently than those with a broad antibody response (P=0.019). 
      CONCLUSIONS: These data show that children with newly diagnosed T1D, who test 
      positive only for IA-2A out of the three molecular antibodies predictive of T1D, 
      have a broader IA-2-specific isotype response and stronger association with the 
      high-risk HLA haplotype than those testing positive for all three molecular 
      antibodies. This may be indicative of a different pathogenetic mechanism in those 
      with their humoral immune response restricted to IA-2 at the time of diagnosis.
FAU - Makinen, Anna
AU  - Makinen A
AD  - Scientific Laboratory, Hospital for Children and Adolescents, University of 
      Helsinki, Helsinki, Biomedicum I, PO Box 63, FI-00014 Helsinki, Finland.
FAU - Harkonen, Taina
AU  - Harkonen T
FAU - Ilonen, Jorma
AU  - Ilonen J
FAU - Knip, Mikael
AU  - Knip M
CN  - Finnish Pediatric Diabetes Register
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Eur J Endocrinol
JT  - European journal of endocrinology
JID - 9423848
RN  - 0 (Autoantibodies)
RN  - 0 (Autoantigens)
RN  - 0 (HLA Antigens)
RN  - 0 (ICA512 autoantibody)
RN  - 0 (Insulin Antibodies)
RN  - 0 (islet cell antibody)
RN  - EC 4.1.1.15 (Glutamate Decarboxylase)
SB  - IM
MH  - Adolescent
MH  - Autoantibodies/immunology
MH  - Autoantigens/*immunology
MH  - Autoimmunity/immunology
MH  - Child
MH  - Child, Preschool
MH  - Diabetes Mellitus, Type 1/genetics/*immunology
MH  - Female
MH  - Finland
MH  - Genetic Predisposition to Disease
MH  - Genotype
MH  - Glutamate Decarboxylase/immunology
MH  - HLA Antigens/genetics
MH  - Humans
MH  - Infant
MH  - Infant, Newborn
MH  - Insulin Antibodies/immunology
MH  - Islets of Langerhans/*immunology
MH  - Male
MH  - Registries
FIR - Knip, Mikael
IR  - Knip M
FIR - Groop, Per-Henrik
IR  - Groop PH
FIR - Ilonen, Jorma
IR  - Ilonen J
FIR - Komulainen, Jorma
IR  - Komulainen J
FIR - Lammi, Else-Maj
IR  - Lammi EM
FIR - Lounamaa, Raisa
IR  - Lounamaa R
FIR - Saha, Marja-Terttu
IR  - Saha MT
FIR - Simell, Olli
IR  - Simell O
FIR - Sipila, Ilkka
IR  - Sipila I
FIR - Talvitie, Timo
IR  - Talvitie T
FIR - Vaarala, Outi
IR  - Vaarala O
FIR - Floman, Peter
IR  - Floman P
FIR - Gustafsson, Brage
IR  - Gustafsson B
FIR - Haapalehto, Maarit
IR  - Haapalehto M
FIR - Holm, Carita
IR  - Holm C
FIR - Johansson, Christian
IR  - Johansson C
FIR - Kaprio, Eero
IR  - Kaprio E
FIR - Kautto, Tuija
IR  - Kautto T
FIR - Keronen, Pirkko
IR  - Keronen P
FIR - Kinnula, Anne
IR  - Kinnula A
FIR - Komulainen, Jorma
IR  - Komulainen J
FIR - Korpela, Paavo
IR  - Korpela P
FIR - Lautala, Pentti
IR  - Lautala P
FIR - Lindstrom, Kaija
IR  - Lindstrom K
FIR - Niemi, Ulla
IR  - Niemi U
FIR - Nuuja, Anja
IR  - Nuuja A
FIR - Nykanen, Paivi
IR  - Nykanen P
FIR - Pontynen, Seppo
IR  - Pontynen S
FIR - Laurila, Anne-Putto
IR  - Laurila AP
FIR - Saha, Marja-Terttu
IR  - Saha MT
FIR - Sankila, Juhani
IR  - Sankila J
FIR - Sipila, Ilkka
IR  - Sipila I
FIR - Taittonen, Leena
IR  - Taittonen L
FIR - Talvitie, Timo
IR  - Talvitie T
FIR - Tapanainen, Paivi
IR  - Tapanainen P
FIR - Uotila, Tapani
IR  - Uotila T
FIR - Uro, Marita
IR  - Uro M
FIR - Varimo, Pentti
IR  - Varimo P
FIR - Wetterstrand, Gunilla
IR  - Wetterstrand G
FIR - Virransalo, Ritva
IR  - Virransalo R
FIR - Vuolukka, Pentti
IR  - Vuolukka P
FIR - Vuorinen, Olli
IR  - Vuorinen O
EDAT- 2008/06/25 09:00
MHDA- 2008/07/17 09:00
CRDT- 2008/06/25 09:00
PHST- 2008/06/25 09:00 [pubmed]
PHST- 2008/07/17 09:00 [medline]
PHST- 2008/06/25 09:00 [entrez]
AID - 159/1/19 [pii]
AID - 10.1530/EJE-07-0853 [doi]
PST - ppublish
SO  - Eur J Endocrinol. 2008 Jul;159(1):19-26. doi: 10.1530/EJE-07-0853.