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Immunogenetics of autoimmune dis

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Immunogenetics of autoimmune dis Powered By Docstoc
					Immunogenetiikan laboratorio

Immunogenetiikan laboratorio on MediCityssä toimiva yksikkö, joka tutkii
immuunivastetta säätelevien geenien toimintaa ja erityisesti näiden merkitystä
autoimmuunitautien synnyssä. Tyypillistä autoimmuunitaudeille on, että myös
ympäristötekijöillä on tärkeä merkitys niiden syntymekanismeissa ja tauti puhkeaakin
perinnöllisen alttiuden ja ympäristövaikutusten yhteisvaikutuksen tuloksena.
Immuunivasteen säätelyssä tärkein yksittäinen geenialue on MHC (major
histocompatibility complex), ihmisellä HLA geenialue. Tämän alueen geenien
polymorfismit määrittävät pitkälti sairastumisalttiutta useiden autoimmuunitautien
kohdalla. Tällaisia sairauksia ovat mm. tyypin 1 diabetes, keliakia, selkärankareuma,
nivelreuma ja multippeliskleroosi. Erityisesti tyypin 1 diabeteksen kohdalla
geneettisen alttiuden määrittämistä on hyödynnetty laajoissa tutkimusprojekteissa,
joissa lisääntyneen sairastumisriskin omaavia lapsia on seurattu tautiin liittyvien
ympäristötekijöiden tunnistamiseksi ja kudosvaurioiden syntyyn liittyvien
mekanismien selvittämiseksi. Laboratorio osallistuu moniin kansallisiin ja
kansainvälisiin tutkimusprojekteihin kuten TRIGR (http://trigr.epi.usf.edu/), DIPP,
FINDIA, PRODIA, TEDDY (http://teddy.epi.usf.edu/) ITN (Immune Tolerance
Network), DIABIMMUNE ja pediatrinen diabetesrekisteri. Laboratorion tutkimuksen
ulkopuolisina rahoittajina ovat mm. Suomen Akatemia, National Institute of Health,
Euroopan Komissio sekä Sigrid Juséliuksen Säätiö. Laboratorion immunogeneettisiä
määrityksiä tehdään myös maksupalvelutoimintana (http://www.med.utu.fi/ylab/)

Laboratorion johtaja: LKT Jorma Ilonen, Turun yliopiston immunogenetiikan
professori (osa-aikainen), Itä-Suomen yliopiston kliinisen mikrobiologian
(immunologia)       professori    (http://www.uku.fi/klmikb/). Sähköposti:
jorma.ilonen@utu.fi

Vanhemmat tutkijat: LT, dos. Robert Hermann, FT Antti-Pekka Laine, LT Johanna
Aarnisalo, FM (väitellyt) Minna Kiviniemi,

Nuoremmat tutkijat ja väitöskirjaopiskelijat: FM Zsofia Gombos, FM Suvi Huttunen,
FM Pauliina Tryykilä, FM Viveka Öling, LuK Mari-Liis Mikk

Tekninen henkilökunta: Mia Karlsson, Terhi Laakso, Terttu Laurén, Piia Nurmi, Anne
Suominen, Ritva Suominen

Viimeaikaiset julkaisut:

2010
Jermendy A, Szatmári I, Laine AP, Lukács K, Horváth KH, Körner A, Madácsy L,
    Veijola R, Simell O, Knip M, Ilonen J, R. Hermann, the Finnish Paediatric Diabetes
    Registry and the HUNT1DGENES program. The interferon-induced helicase
    (IFIH1) Ala946Thr polymorphism is associated with type 1 diabetes both in the
    high incidence Finnish and the medium incidence Hungarian population.
    Diabetologia 2010;53:98-102
Nwaru BI, Ahonen S, Kaila M, Erkkola M, Haapala A-M, Kronberg-Kippilä C, Veijola
    R, Ilonen J, Simell O, Knip M, Virtanen SM. Maternal diet during pregnancy and
    allergic sensitization in the offspring by 5 years of age: a prospective cohort study.
    Pediatr Allergy Immunol 2010;21:29-37
Savilahti E, Ilonen J, Kiviniemi M, Saarinen KM, Vaarala O, Savilahti E. HLA-(DR1)-
    DQB1*0501 and (DR15)-DQB1*0602 haplotypes are associated with humoral
    responses to early food allergens in children. Int Arch Allergy Imm 2010;152:169-
    177
Virtanen S, Kaila M, Pekkanen J, Kenward M, Uusitalo U, Pietinen P, Kronberg-
    Kippilä C, Hakulinen T, Simell O, Ilonen J, Veijola R, Knip M. Early introduction
    of oats associated with decreased risk of persistent asthma and early introduction of
    fish with decreased risk of allergic rhinitis. Brit J Nutr 2010;103:266-273
Nwaru BI, Erkkola M, Ahonen S, Kaila M, Haapala A-M, Kronberg-Kippilä C,
    Salmelin R, Veijola R, Ilonen J, Simell O, Knip M, Virtanen SM. Age at
    introduction of solid foods during the first year of life and allergic sensitization at
    age 5 years: a prospective cohort study. Pediatrics; Epub ahead of print
Simell S, Hoppu S, Simell T, Ståhlberg M-R, Viander M, Routi T, Simell V, Veijola R,
    Ilonen J, Hyöty H, Knip M, Simell O. Age at development of type 1 diabetes and
    celiac disease-associated autoantibodies and clinical disease in genetically
    susceptible children observed from birth. Diabetes Care, Epub ahead of print
Kordonouri O, Hartmann R, Charpentier N, Knip M, Danne T, Ilonen J. Genetic risk
    markers related to diabetes-associated autoantibodies in young patients with type 1
    diabetes in Berlin, Germany. Exp Clin Endocr Diab, in press
Öling V, Geubtner K, Ilonen J, Reijonen H. A low antigen dose selectively promotes
    expansion of high avidity autoreactive T cells: study of the DRB1*0404-restricted
    human T cells specific to GAD65. Autoimmunity, in press

2009
Doroudis K, Laine AP, Heinonen M, Hermann R, Lipponen K, Veijola R, Simell O,
     Knip M, Uibo R, Ilonen J, Kisand K. Association of CTLA4 but not ICOS
     Polymorphisms with Type 1 Diabetes in Two Populations with Different Disease
     Rates. Hum Immunol 2009;70:536-539
Erkkola M, Kaila M, Nwaru B, Kronberg-Kippilä C, Ahonen S, Nevalainen J, Veijola
     R, Pekkanen J, Ilonen J, Simell O, Knip M, Virtanen S. Maternal vitamin D intake
     during pregnancy is inversely associated with asthma and allergic rhinitis in 5-year-
     old children. Clin Exp Allergy 2009;39:875-882
Ilonen J, Kocova M, Lipponen K, Sukarova-Angelovska E, Jovanovska A, Knip M.
     HLA-DR-DQ haplotypes and type 1 diabetes in Macedonia. Hum Immunol
     2009;70:461-463
Kiviniemi M, Ilonen J, Lövgren T. A homogeneous HLA-B*27 genotyping assay using
     dried reagent mixtures. Disease Markers 2009;27:85-91
Lempainen J, Vaarala O, Mäkelä M, Veijola R, Simell O, Knip M, Hermann R, Ilonen
     J. Interplay between PTPN22C1858T polymorphism and cow´s milk formula
     exposure in type 1 diabetes. J Autoimmun 2009;33:155-164
Siljander H, Härkönen T, Hermann R, Simell S, Hekkala A, Salonsaari R-T, Simell T,
     Simell O, Ilonen J, Veijola R, Knip M. Role of insulin autoantibody affinity as a
     predictive marker for type 1 diabetes in young children with HLA-conferred disease
     susceptibility. Diab/Metab Res Rev 2009;25:615-622
Siljander HTA, Simell S, Hekkala A, Lähde J, Simell T, Vähäsalo P, Veijola R, Ilonen
     J, Simell O, Knip M. Predictive characteristics of diabetes-associated
     autoantibodies among children with HLA-conferred disease susceptibility in the
     general population. Diabetes 2009;58:2835-2842
Thorn L, Forsblom C, Wadén J, Söderlund J, Rosengård-Bärlund M, Saraheimo M,
     Heikkilä O, Hietala K, Petterson-Fernholm K, Ilonen J, Groop P-H. Effect of
    parental type 2 diabetes on offspring with type 1 diabetes. Diabetes Care
    2009;32:63-68

2008
Aarnisalo J, Veijola R, Vainionpää R, Simell O, Knip M, Ilonen J. Cytomegalovirus
    infection in early infancy: risk or induction and progression of autoimmunity
    associated with type 1 diabetes. Diabetologia 2008;51:769-772
Aarnisalo J, Treszl A, Svec P, Marttila J, Öling V, Simell O, Knip M, Körner A,
    Madacsy L, Vasarhelyi B, Ilonen J, Hermann R. Reduced CD4+ T cell activation in
    children with type 1 diabetes carrying the PTPN22/Lyp 620Trp variant. J
    Autoimmun 2008;31:13-21
Aittoniemi J, Turpeinen H, Tiittanen M, Knip M, Simell O, Ilonen J, Vaarala O.
    Relation among mannose-binding lectin 2 genotype, beta-cell autoantibodies and
    risk for type 1 diabetes in Finnish children. Hum Immunol 2008;69:108-11
Gullstrand C, Wahlberg J, Ilonen J, Vaarala O, Ludvigsson J. Progression to type 1
    diabetes and autoantibody positivity in relation to HLA risk genotypes in children
    participating in the ABIS study. Pediatric Diabetes 2008;9:182-190
Kondrashova A, Viskari H, Haapala A-M, Seiskari T, Kulmala P, Ilonen J, Knip M,
    Hyöty H. Serological evidence of thyroid autoimmunity among schoolchildren in
    two different socio-economic environments. J Clin Endocrinol Metab 2008;93:729-
    34
Kondrashova A, Mustalahti L, Kaukinen K, Viskari H, Volodicheva V, Haapala AM,
    Ilonen J, Knip M, Mäki M, Hyöty H, EPIVIR Study Group. Lower economic status
    and inferior hygienic environment may protect against celiac disease. Ann Med
    2008;40:223-231
Koskela RM, Karttunen TJ, Niemelä SE, Lehtola JK, Ilonen J, Karttunen RA. HLA and
    TNFalpha polymorphism association in microscopic coalities. Eur J Gastroenterol
    Hepatol 2008;20:276-282
Lundberg A, Andersson Wikberg L, Ilonen J, Vaarala O, Fagerås Böttcher M.
    Lipopolysaccharide induced immune responses in relation to TLR4 Asp299Gly
    gene polymorphism. Clin Vacc Immunol 2008;15:1878-1883
Luopajärvi K, Savilahti E, Virtanen SM, Ilonen J, Knip M, Åkerblom HK, Vaarala O.
    Enhanced levels of cow´s milk antibodies in infancy in children who develop type 1
    diabetes later in childhood. Pediatric Diabetes 2008;9:434-441
Marttila J, Huttunen S, Vaarala O, Suzuki K, Elliott JF, Närvänen A, Knip M, Simell O,
    Ilonen J. T-cell reactivity to insulin peptide A1-12 in children with recently
    diagnosed type 1 diabetes or multiple autoantibodies. J Autoimmun 2008;31:142-
    148
Mäkinen A, Härkönen T, Ilonen J, Knip M, the Finnish Paediatric Diabetes Register.
    Characterization of the humoral immune response to IA-2 in children with newly
    diagnosed type 1 diabetes, Eur J Endocrinol 2008;159:19-26
Näntö-Salonen K, Kupila A, Simell S, Siljander H, Salonsaari T, Hekkala A, Korhonen
    S, Erkkola R, Sipilä JI, Haavisto L, Siltala M, Tuominen J, Hakalax J, Hyöty H,
    Ilonen J, Veijola R, Simell T, Knip M, Simell O. Can type 1 diabetes be prevented
    by a tolerisation strategy: nasal insulin in children with genetic risk and
    autoantibodies. Lancet 2008;372:1746-1755
Oikarinen M, Tauriainen S, Honkanen T, Vuori K, Karhunen P, Vasama-Nolvi C,
    Oikarinen S, Verbeke C, Blair GE, Rantala I, Ilonen J, Simell O, Knip M, Hyöty H.
    Analysis of pancreas tissue in a child positive for islet cell antibodies. Diabetologia
    2008;51:1796-1802
Oresic M, Simell S, Sysi-Aho, M, Näntö-Salonen K, Seppänen-Laakso T, Parikka V
    Katajamaa M, Hekkala A, Mattila O, Keskinen P, Yetukuri L, Reinikainen A,
    Lähde J, Suortti T, Hakalax J, Simell T, Hyöty H, Veijola R, Ilonen J, Lahesmaa R,
    Knip M, Simell O. Dysregulation of lipid and amino acid metabolism precedes islet
    autoimmunity in children who later progress to type 1 diabetes. J Exp Med,
    2008;205:2975-2984
Tauriainen S, Oikarinen S, Taimen K, Laranne J, Sipilä M, Lönnrot M, Ilonen J, Simell
    O, Knip M, Hyöty H. Temporal relationship between human parechovirus 1
    infection and otitis media in young children. J Infect Dis 2008;198:35-40
Uusitalo L, Nevalainen J, Niinistö S, Alfthan G, Sundvall J, Korhonen T, Kenward MG,
    Oja H, Veijola R, Simell O, Ilonen J, Knip M, Virtanen SM. Serum a- and g-
    tocopherol concentrations and risk of advanced beta cell autoimmunity in children
    with HLA-conferred susceptibility to type 1 diabetes mellitus. Diabetologia
    2008;51:773-780
Uusitalo L, Kenward MG, Virtanen SM, Uusitalo U, Nevalainen J, Niinistö S,
    Kronberg-Kippilä C, Ovaskainen M-L, Simell O, Ilonen J, Veijola R, Knip M.
    Intake of antioxidant vitamins and trace elements during pregnancy and risk of
    advanced beta-cell autoimmunity in the child. Am J Clin Nutr 2008;88:458-464
Vallittu AM, Erälinna JP, Ilonen J, Salmi AA, Waris M. MxA protein assay for optimal
    monitoring of IFN-beta bioactivity in the treatment of MS patients. Acta Neurol
    Scand 2008;118-12-17
Walldén J, Ilonen J, Roivainen M, Ludvigsson J, Vaarala O, the ABIS Study Group.
    Effect of HLA genotype or CTLA-4 polymorphism on cytokine response in healthy
    children, Scand J Immunol 2008;68:345-350
Walldén J, Honkanen J, Ilonen J, Ludvigsson J, Vaarala O. No evidence for activation
    of TH1 or TH17 pathways in unstimulated peripheral blood mononuclear cells from
    children with ß-cell autoimmunity or T1D. J Inflamm Res 2008;1:11-17

2007
Ankelo M, Westerlund A, Blomberg K, Knip M, Ilonen J, Hinkkanen AE. Time-
    resolved immunofluorometric dual-label assay for simultaneous detector of
    autoantibodies to GAD65 and IA-2 in children with type 1 diabetes. Clin Chem
    2007;53:472-479
Ankelo M, Kleimola V, Simell S, Simell O, Knip M, Jokisalo E, Tarkia M,
    Westerlund A, He Q, Viander M, Ilonen J, Hinkkanen AE. Antibody responses to
    gliadin peptide show high specificity and paraller antibodies to transglutaminase 2
    in developing celiac disease. Clin Exp Immunol, 2007;150:285-293
Gombos Z, Hermann R, Kiviniemi M, Nejentsev S, Reimand K, Fadeyev V, Peterson
    P, Uibo R, Ilonen J. Analysis of extended HLA haplotypes associated with
    Addison´s disease in three populations. Eur J Endocrinol 2007;157:757-761
Kiviniemi M, Hermann R, Nurmi J, Ziegler AG, Knip M, Simell O, Veijola R,
    Lövgren T, Ilonen J, the TEDDY Study Group. A high-throughput population
    screening system for the estimation of genetic risk for type 1 diabetes. An
    application for the TEDDY (The Environmental Determinants of Diabetes in the
    Young) study. Diabetes Technology and Therapeutics 2007;9:460-472
Kondrashova A, Viskari H, Kulmala P, Romanov A, Ilonen J, Hyöty H, Knip M. Signs
    of beta-cell autoimmunity in non-diabetic schoolchildren: A comparison between
    Russian Karelia with a low incidence of type 1 diabetes and Finland with a high
    incidence rate. Diabetes Care 2007;30:95-100
Laine AP, Holmberg H, Nilsson A, Örtqvist E, Kiviniemi M, Vaarala O, Åkerblom
    HK, Simell O, Knip M, Ludvigsson J, Ivarsson S-A, Larsson K, Lernmark Å,
    Ilonen J, the Finnishh Paediatric Diabetes Registry. Two insulin gene single
    nucleotide polymorphisms associated with type 1 diabetes risk in the Finnish and
    Swedish populations. Disease Markers 2007;23:139-145
Luopajärvi K, Skarsvik S, Ilonen J, Åkerblom HK, Vaarala O. Reduced CCR4, IL-13
    and GATA-3 upregulation in response to type 2 cytokines of cord blood T
    lymfocyten in infants at genetic risk of type 1 diabetes. Immunology
    2007;121:189-196
Mähönen S-M, Sironen T, Vapalahti O, Pääkkö E, Hautala N, Ilonen J, Glumoff V,
    Vainio O, Kauma H, Vaheri A, Plyusnin A, Hautala T. Puumala virus RNA in
    cerebrospinal fluid of a patient with uncomplicated nephropathia epidemica. J
    Clin Virol 2007;40:248-251
Öling V, Marttila J, Knip M, Simell O, Ilonen J. Circulating CD4+CD25high regulatory
    T cells and natural killer T cells in children with newly diagnosed type 1 diabetes
    or with diabetes-associated autoantibodies. Ann NY Acad Sci 2007;1107:363-372
Simell S, Hoppu S, Hekkala A, Simell T, Ståhlberg MR, Viander M, Yrjänäinen H,
    Grönlund J, Markula P, Simell V, Knip M, Ilonen J, Hyöty H, Simell O. Fate of
    five celiac disease-associated antibodies during normal diet in genetically at-risk
    children observed from birth in a natural history study. Am J Gastroenterol
    2007;102:1026-2035
Tauriainen S, Martiskainen M, Oikarinen S, Lönnrot M, Viskari H, Ilonen J, Simell O,
    Knip M, Hyöty H. Human parechovirus 1 infections in young children – no
    association with type 1 diabetes. J Med Virol 2007;79:457-462
Thomson G, Valdes AM, Noble JA, Grote MN, Najman J, Erlich HA, Cucca F,
    Pugliese A, Steenkiste A, Dorman JS, Caillat-Zucman S, Hermann R, Ilonen J,
    Lambert AP, Bingley PJ, Gillespie KM, Lernmark Å, Kockum I, Sanjeevi CB,
    Rønningen KS, Undlien DE, Thorsby E, Petrone EA, Buzzetti R, Koeleman BPC,
    Roep BO, Saruhan-Direskeneli G, Uyar FA, Günoz H, Gorodezky C, Alaez C,
    Boehm BO, Mlynarski, H. Ikegami, M. Berrino, M.E. Fasano, E. Dametto, S.
    Israel, C. Brautbaur W, Santiago-Cortes A, Frazer de Llado T, She J-X, Bugawan
    TL, Rotter JI, Raffel L, Zeidler A, Leyva-Cobian F, Hawkins BR, Chan SH,
    Castano L, Pociot F, Nerup J. Relative predispositional effects of HLA class II
    DRB1-DQB1 haplotypes and genotypes on type 1 diabetes: a meta-analysis.
    Tissue Antigens 2007;70:110-127
Westerlund A, Ankelo M, Simell S, Ilonen J, Simell O, Hinkkanen AE. Affinity
    maturation of immunoglobulin A anti-tissue transglutaminase autoantibody during
    development of celiac disease. Clin Exp Immunol 2007;148:230-240
Åkerblom HK, Knip M, Becker D, Dosch H-M, Dupré J, Ilonen J, Krischer JP,
    TRIGR Study Group. The TRIGR Trial: Testing the potential link between
    weaning diet and type 1 diabetes. (R) Immun Endoc & Metab Agents in Med
    Chem 2007;7:251-263

				
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