Alnek, Kristi

Laht, Brita

Lubi, Maire

Mandel, Maire

Metsküla, Kaja

Reppo, Ingrid

Talja, Irja

Uibo, Raivo

English

Journals from University of Tartu

235EEsti uuringuid ma ailma tEadusajakirjadEsEesti Arst 2023; 102(4):235* Tegu on pilditõmmisega artikli päisest.1 TÜ bio- ja siirdemeditsiini instituut, 2 TÜ kliinilise meditsiini instituut, 3 TÜ Kliinikumi sisekliinikÄsja diagnoositud 1. tüüpi diabeeti põdevatel täiskasvanutel ja lastel on IgA-tüüpi enteroviirustevastaste antikehade hulk suurenenud*TaustEsimest tüüpi diabeet (T1D) on kroo­niline immuunvahendatud haigus, mille tekkes omavad rolli geenid ja keskkond. Peamine geneetiline riskitegur on seotud inimese leuko­tsüütide antigeeni (HLA) kompleksi regiooniga. Keskkonnateguritest võivad haigust käiv itada vähene v itamiinide tarbimine, r innaga toitmine, kõrge sünnikaal, kokku­puude lehmapiimaga, soolestiku mikrobioom ja viirused. Mitmete uuringute põhjal peetakse entero­viiruseid (EV) peamiseks teguriks lapseea T1D tekkes. Seni pole teada, kas ka täiskasvanutel on v i irus haiguse tekkega seotud. Kirjanduses pole pi isava lt andmeid EVde ja T1D­ga seotud geenipolümorfismide seoste kohta, näiteks seoste kohta PTPN22­ga (protein tyrosine phos­phatase nonreceptor type 22), mis on oluline immuunvastuse modulaator, ja IFIH1­ga (interferon induced with helicase C domain 1), mis on üks keskseid v i irusinfektsioonidega seotud geene. Need geneetilised ja keskkonnategurid võivad põhjustada Langerhansi saarekeste vastaste autoantikehade teket juba enne T1D diagnoosimist.Uuringu eesmärk oli välja selgi­tada EV­vastaste antikehade levimus äsja diagnoositud T1D­ga patsientidel erinevates vanuserühmades ja neile sobitatud kontrollisikutel. Samuti seati eesmärgiks uurida PTPN22 (rs2476601) ja IFIH1 (rs1990760) genotüüpide ning autoimmuunsete tunnuste jaotumist ja leida nende seosed EV antikehadega.MetoodikaUuringusse kaasati äsja diagnoositud T1D­ga (n = 62) ning neile vanuse, soo ja HLA riski genotüübi alusel sobi­tatud kontrollisikud (n = 62), kelle vanus jäi alla 35 aasta. EV­vastased antikehad (immuunglobuliin A ehk IgA, IgG ja IgM) ja T1D­ga seotud antikehad määrati ensüümvahen­datud immunosorptsioonimeetodiga (ELISA). IgA­ ja IgG­tüüpi EV­antike­hade määramiseks kasutati antigee­nina KEVPALTAVETGAT peptiidi. HLA genotüpiseerimine viidi läbi polüme­raasi ahelreaktsiooniga (PCR), mis põhineb lantaniidiga märgistatud oligonukleotiidi hübridisatsioonil ja ajaresolutsiooniga fluorestsents­testil. Geenipolümorfismid määrati TaqMan Genotyping assay abil.TulemusedUuringu tu lemusena selgus, et 46,8% T1D­ga isikutel (mediaan­väärtus 10,9 EIU) ja 11,3% kont­rollidel (mediaanväärtus 3,4 EIU) ol id IgA­tüüpi EV­vastased anti­kehad olemas. EV­vastaste IgA­tüüpi antikehade leid (šansisuhe (OR) 8,33; 95% usaldusvahemik (uv) 2,52–27,6; p = 0,0005) ja anti­kehade kõrgenenud tase (OR 1,04; 95% uv 1,01–1,06; p = 0,0105) olid oluliseks riskiteguriks T1D puhul. IgA­tüüpi EV­vastaste antikehade levimus laste (0–18,9 a) ja noorte täiskasvanute (19–35,9 a) seas oli samuti erinev (vastavalt p = 0,0089 ja p = 0,0055). EV­vastaste IgG­ ega IgM­tüüpi antikehade vahel sellist erinevust ei leitud. Oluline seos leiti ka EV antikehade ja T1D­ga seotud autoantikehade vahel. PTPN22 ja IFIH1 genotüüpide sageduse ning EV antikehade vahel seost ei leitud. KokkuvõteTööst järeldus, et EV­infektsioonid võivad olla oluliseks T1D­d soodus­tavaks teguriks mitte ainult lapse­, vaid ka täiskasvanueas. Leitud seose kinnitamiseks on vajalikud edasised viroloogilised uuringud täiskasvanud T1D­haigete hulgas. Research ArticleIgA-Type Enterovirus Antibodies Are Increased among Adultsand Children with Recently Diagnosed Type 1 DiabetesKristi Alnek ,1 Ija Talja,1 Brita Laht,1 Kaja Metsküla,1 Maire Mandel,1 Ingrid Reppo,2,3Maire L bi,2,3 and Raivo Uibo 11Department of Immunology, Institute of Bio- and Translatio al Medicine, University of Tartu, 19 Ravila, Tartu 50411, Estonia2Department of Internal Medicine, Institute of Clinical Medicine, University of Tartu, 8 L. Puusepa, Tartu 50406, Estonia3Internal Medicine Clinic of Tartu University Hospital, 8 L. Puusepa, Tartu 50406, EstoniaCorrespondence should be addressed to Raivo Uibo; raivo.uibo@ut.eeReceived 23 December 2021; Accepted 15 July 2022; Published 30 July 2022Academic Editor: Mirosława Ferens-SieczkowskaCopyright © 2022 Kristi Alnek et al. This is an open access article distributed under the Creative Commons Attribution License,which permits unrestricted use, distribution, and reprod ction in any medium, provided the original work is properly cited.Enteroviruses (EV) are among the leading environmental triggers of childhood-onset type 1 diabetes (T1D). Our aim was todetermine the prevalence of antibodies against EV and their association with T1D in different age groups (n = 62), includingyoung adults, a d to comp re these data with results from LA-matched control participants (n = 62). IgA, IgG, and IgMantibodies against EV were detected. IgA EV antibodies were present in 46.8% of participants with T1D (median level 10.9EIU) and in 11.3% of controls (median level 3.4 EIU). IgA EV positivity and higher level of IgA EV antibodies were bothsignificant risk factors for T1D (odds ratio (OR) 8.33; 95% confidence interval (CI) 2.52–27.6; p = 0:0005 and OR 1.04; 95% CI1.01–1.06; p = 0:0105, respectiv ly). Importantly, the prevalence of IgA EV antibodies in the subgroups of both children andyoung adults was also significantly different between participants with T1D and their matched controls (p = 0:0089 and p =0:0055, respectively). Such differences were not seen for IgG and IgM EV antibodies. However, IgG EV antibodies wereassociated with 65 kDa glutamic acid decarboxylase antibodies, but not with zinc transporter 8 and protein tyrosinephosphatase IA2 antibodies. The genotype frequency of PTPN22 (rs2476601) and IFIH1 (rs1990760) was not associated withEV positivity. This study showed that EV infections may be an important disease-pro oting factor of T1D not only inchildhood-onset but also in adult-onset T1D. However, to further confirm thi association, direct virological studies are neededin the latter T1D group.1. IntroductionType 1 diabetes (T1D) is a chronic immune-mediated disor-der characterized by progressive destruction of insulin-producing β-cells. The major genetic risk for T1D is relatedto the human leukocyte antigen (HLA) complex, where thecombination of HLA cla s II alleles DRB1∗03/DQB1∗0201and DRB1∗04/DQB1∗0302 confers the greatest risk [1].However, a previous Finnish study has shown that this highrisk genotype was only detected in 21% of T1D cases [2]. Ithas also been suggested that environmental factors such aslow v tamin intake, cow’s milk exposure, breastfeeding,toxins, high birth weight, gut microbiome, and viruses aretriggers for onset of the disease [1, 3].Enteroviruses (EV) are considered the leading candi-dates according to numerous studies performed in chil-dren [4–6]. The association of EV with T1D has beenconfirmed both by the presence of EV protein in the pan-creatic tissue [7] and by serum antibodies to EV in T1D[8, 9]. However, it is not fully known whether T1D inadults is associated with EV. There are no sufficient dataabout the role of other T1D susceptibility genes in themodulation of EV infections among the adult population.In this context, interferon induced with helicase C domain1 (IFIH1) protein, a sensor for EV infection [5, 10], andprotein tyrosine phosphatase nonreceptor type 22(PTPN22), a significant m dulator of immune response[5, 11], deserve special attention. The role of both genesHindawiBioMed Research InternationalVolume 2022, Article ID 7603062, 8 pageshttps://doi.org/10.1155/2022/7603062Research ArticleIgA-Type Enterovirus Antibodies Are Increased among Adultsand Children with Recently Diagnosed Type 1 DiabetesKristi Alnek ,1 Ija Talja,1 Brita Laht,1 Kaja Metsküla,1 Maire Mandel,1 Ingrid Reppo,2,3Maire Lubi,2,3 and Raivo Uibo 11Department of Immunology, Institute of Bio- and Translational Medicine, University of Tartu, 19 Ravila, Tartu 50411, Estonia2Department of Internal Medicine, Institute of Clinical Medicine, University of Tartu, 8 L. Puusepa, Tartu 50406, Estonia3Internal Medicine Clinic of Tartu University Hospital, 8 L. Puusepa, Tartu 50406, EstoniaCorrespondence should be addressed to Raivo Uibo; raivo.uibo@ut.eeReceived 23 December 2021; Accepted 15 July 2022; Published 30 July 2022Academic Editor: Mirosława Ferens-SieczkowskaCopyright © 2022 Kristi Alnek et al. This is an open access article distributed under the Creative Commons Attribution License,which perm ts unrestricted use, distribution, and reproduction in any medium, provided the original work s properly cited.Enteroviruses (EV) are among the leading environmental triggers of childhood-onset type 1 diabetes (T1D). Our aim was todetermine the prevalence of antibodies against EV and their association with T1D in different age groups (n = 62), includingyoung adults, and to compare these data with results from HLA-matched control participants ( = 62). IgA, IgG, and IgMantibodies against EV were detected. IgA EV antibodies were present in 46.8% of participants with T1D (median level 10.9EIU) and in 11.3% of controls (median level 3.4 EIU). IgA EV positivity and higher level of IgA EV antibodies were bothsignificant risk factors for T1D (odds ratio (OR) 8.33; 95% confidence interval (CI) 2.52–27.6; p = 0:0005 and OR 1.04; 95% CI1.01–1.06; p = 0:0105, respectively). Importantly, the prevalence of IgA EV antibodies in the subgroups of both children andyoung adults was als significantly different between participants with T1D and their matched controls (p = 0:0089 and p =0:0055, respectively). Such differences were not seen for IgG and IgM EV antibodies. However, IgG EV antibodies wereassociated with 65 kDa glutamic acid decarboxylase antibodies, but not with zinc transporter 8 and protein tyrosinephosphatase IA2 antibodies. The genotype frequency of PTPN22 (rs2476601) and IFIH1 (rs1990760) was not associated withEV positivity. This study showed that EV infections may be an important disease-promoting factor of T1D not only inchildhood-onset but a so in a ult-onset T1D. However, to further confirm thi association, direct virological studies are neededin the latter T1D group.1. IntroductioType 1 diabetes (T1D) is a chronic immune-mediated disor-der characterized by progressive destruction of insulin-producing β-cells. The major genetic risk for T1D is relatedto the human leukocyte antigen (HLA) complex, where thecombin tio of HLA class II alleles DRB1∗03/DQB1∗0201and DRB1∗04/DQB1∗0302 co fers the greatest risk [1].However, a previous Finnish study has show that this highrisk genotype was only detected in 21% of T1D cases [2]. Ithas also been suggested that environmental factors such aslow vitamin intake, cow’s milk exposure, breastfeeding,toxins, high birth weight, gut microbiome, and viruses aretriggers for onset of the disease [1, 3].Entero iruses (EV) are considered the leading candi-dates according to numerous studies performed in chil-dren [4–6]. The association of EV with T1D has beenconfirmed both by the presence of EV protein in the pan-creatic tissue [7] and by serum antibodies to EV in T1D[8, 9]. However, it is not fully known whether T1D inadults is associated with EV. There are no sufficient dataabout the role of other T1D susceptibility genes in themodulation of EV infections among the adult population.In this context, interferon induced with helicase C domain1 (IFIH1) protein, a sensor for EV infection [5, 10], andprotein tyrosine phosphatase nonreceptor type 22(PTPN22), a sig ificant modulator of immune response[5, 11], deserve special atte t on. The role of both gen sHindawiBioMed Research InternationalVolume 2022, Article ID 7603062, 8 pageshttps://doi.org/10.1155/2022/7603062Research ArticleIgA-Type Enterovirus Antibodies Are Increased among Adultsand Children with Recently Diagnosed Type 1 DiabetesKristi Alnek ,1 Ija Talja,1 Brita Laht,1 Kaja Metsküla,1 Maire Mandel,1 Ingrid Reppo,2,3Maire Lubi,2,3 and Raivo Uibo 11Department of Immunology, Institute of Bio- and Translational Medicine, University of Tartu, 19 Ravila, Tartu 50411, Estonia2Department of Internal Medicine, Institute of Clinical Medicine, University of Tartu, 8 L. Puusepa, Tartu 50406, Estonia3Internal Medicine Clinic of Tartu University Hospital, 8 L. Puusepa, Tartu 50406, EstoniaCorrespondence should be addressed to Raivo Uibo; raivo.uibo@ut.eeReceived 23 December 2021; Accepted 15 July 2022; Published 30 July 2022Academic Editor: Mirosława Ferens-SieczkowskCopyright © 2022 Kristi Alnek et al. This is an open access article distributed under the Creative Commons Attribution License,which permits unrestricted use, distribution, and reproductio in any medium, provided the original work is properly cited.Enteroviruses (EV) are among the leading environmental triggers of childhood-onset type 1 diabetes (T1D). Our aim was todetermine the prevalence of antibodies against EV and their association with T1D in different age groups (n = 62), includingyoung adults, and to compare these d ta with results from HLA-matched control participants (n = 62). I A, IgG, and IgMantibodies against EV were dete ted. IgA EV antibodies were present in 46.8% of participants with T1D (median level 10.9EIU) and in 11.3% of co trols (m dian l vel 3.4 EIU). IgA EV positivity and higher level of IgA EV antibodies were bothsignificant risk factors for T1D (odds ratio (OR) 8.33; 95% confidence interval (CI) 2.52–27.6; p = 0:0005 and OR 1.04; 95% CI1.01–1.06; p = 0:0105, respe tively). Importantly, the prevalence of IgA EV antibodies in the subgroups of both children andyoung adults was also significantly different between participants with T1D and their matched controls (p = 0:0089 and p =0:0055, respectively). Such differences were not se for IgG and IgM EV antibodies. However, IgG EV antibodies wereassociated with 65 kDa glutamic aci decarboxylas antibodies, but not with zinc transporter 8 and protein tyrosinephosphatase IA2 antibodies. The genotype frequency of PTPN22 (rs2476601) and IFIH1 (rs1990760) was not associated withEV positivity. T is study showed that EV infections may be an important disease-promoting factor of T1D not nly inchildhood-onset but also in adult-onset T1D. However, to further confirm this association, direct vir logical studies are neededin the latter T1D group.1. Introduct onType 1 diabetes (T1D) is a chronic immune-mediated disor-der characterized by pr gressive destruction of insulin-producing β-cells. Th major genetic i k for T1D is relatedto the human leukocyte antigen (HLA) complex, where thecombinati n of HLA class II all les DRB1∗03/DQB1∗0201and DRB1∗04/DQB1∗0302 confers the greatest risk [1].Howev r, a pr vious Finnish study has shown that t is highrisk genotype was only detected in 21% of T1 cases [2]. Ihas also been suggested that environm ntal factors such aslow vitamin intake, cow’s milk exposure, breas feeding,toxins, high birth weight, gut microbiome, and viruses aretriggers for o set of the diseas [1, 3].Enteroviruses (EV) are considered the leading candi-dates according to numerous studies performed in chil-dren [4–6]. The association of EV with T1D has beenconfirmed both by the pr sence of EV protein in the pan-creatic tissue [7] and by serum antibodies to EV in T1D[8, 9]. However, it is not fully known whether T1D inadults is associated ith EV. There are no sufficient dataabout the role of other T1D susceptibility genes in themodulation of EV nfect ns among the adult population.In t is context, interferon induced with helicase C domain1 (IFIH1) protein, a sensor for EV infe tion [5, 10], andprotein tyrosine h sphat se nonreceptor type 22(PTPN22), a significant modulator of immune r sp nse[5, 11], deserve speci l attentio . The role of both genesHindawiBioMed Research InternationalVolume 2022, Article ID 7603062, 8 pageshttps://doi.org/10.1155/2022/7603062

Äsja diagnoositud 1. tüüpi diabeeti põdevatel täiskasvanutel ja lastel on IgA-tüüpi enteroviirustevastaste antikehade hulk suurenenud

https://ojs.utlib.ee/index.php/EA/article/download/22440/17020

Äsja diagnoositud 1. tüüpi diabeeti põdevatel täiskasvanutel ja lastel on IgA-tüüpi enteroviirustevastaste antikehade hulk suurenenud

Abstract

Similar works

Full text

Available Versions

Journals from University of Tartu