186-OR: Novel Autoantibodies to Deamidated IA2 Extracellular Domain in Type 1 Diabetes
Background: Insulinoma antigen-2 (IA2) is a major self-antigen in T1D with post translational modification (PTM) of the extracellular domain (IA2ec) by deamidation eliciting T cell responses in T1D patients. Yet the autoantibodies (Abs) to these IA2ec PTM epitopes in T1D has not been studied. Method...
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| Veröffentlicht in: | Diabetes (New York, N.Y.) N.Y.), 2022-06, Vol.71 (Supplement_1) |
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| container_title | Diabetes (New York, N.Y.) |
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| creator | JIA, XIAOFAN MIAO, DONGMEI ZHANG, CAIGUO MICHELS, AARON W. YU, LIPING WENZLAU, JANET M. |
| description | Background: Insulinoma antigen-2 (IA2) is a major self-antigen in T1D with post translational modification (PTM) of the extracellular domain (IA2ec) by deamidation eliciting T cell responses in T1D patients. Yet the autoantibodies (Abs) to these IA2ec PTM epitopes in T1D has not been studied.
Methods: IA2ec protein containing all the four T-cell responsive deamidated Q>E epitopes (aa 198-216, 467-482, 523-536 and 545-562) was produced. Sera from 269 new onset T1D children (median age= 12.6yrs) and 3age-matched healthy children were tested for Abs to IA2ecQ>E and wide type (WT) IA2ec with radiobinding assay (RBA) .
Results: The assay cut-offs were set at the 99th percentile for both IA2ecQ>E Ab and IA2ecWT Ab. In T1D children, positivity for IA2ecQ>E Ab was 60.6% (163/269) vs. IA2ecWT Ab 19.3% (52/269, PE Ab were significantly higher than IA2ecWT Ab (Fig) , 58% (91/157) vs. 15.3% (24/157, PE Ab is potentially a new novel predictive and diagnostic biomarker for T1D. |
| doi_str_mv | 10.2337/db22-186-OR |
| format | Article |
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Methods: IA2ec protein containing all the four T-cell responsive deamidated Q>E epitopes (aa 198-216, 467-482, 523-536 and 545-562) was produced. Sera from 269 new onset T1D children (median age= 12.6yrs) and 3age-matched healthy children were tested for Abs to IA2ecQ>E and wide type (WT) IA2ec with radiobinding assay (RBA) .
Results: The assay cut-offs were set at the 99th percentile for both IA2ecQ>E Ab and IA2ecWT Ab. In T1D children, positivity for IA2ecQ>E Ab was 60.6% (163/269) vs. IA2ecWT Ab 19.3% (52/269, P<0.0001) . In two subgroups of T1D patients who were positive (n=157) or negative (n=112) for current Abs to IA2 intra-cellular domain (IA2ic) , the positivity of IA2ecQ>E Ab were significantly higher than IA2ecWT Ab (Fig) , 58% (91/157) vs. 15.3% (24/157, P<0.0001) and 64.3% (72/112) vs. 25% (28/112, p<0.0001) . However, the positivity of IA2ec Ab did not differ between the patients with or without IA2ic Ab.
Conclusion: IA2ecQ>E Ab was detected in a large proportion of T1D patients, independent of the prototypical IA2ic Ab. IA2ecQ>E Ab is potentially a new novel predictive and diagnostic biomarker for T1D.</description><identifier>ISSN: 0012-1797</identifier><identifier>EISSN: 1939-327X</identifier><identifier>DOI: 10.2337/db22-186-OR</identifier><language>eng</language><publisher>New York: American Diabetes Association</publisher><subject>Antigens ; Autoantibodies ; Autoantigens ; Children ; Diabetes ; Diabetes mellitus (insulin dependent) ; Epitopes ; Insulinoma ; Lymphocytes T ; Neuroendocrine tumors</subject><ispartof>Diabetes (New York, N.Y.), 2022-06, Vol.71 (Supplement_1)</ispartof><rights>Copyright American Diabetes Association Jun 2022</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c1062-56e1ef2c2ef7f6e7cb0337cbb9a0b1ce1223a52a8f81b07bc74a706ff18def703</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids></links><search><creatorcontrib>JIA, XIAOFAN</creatorcontrib><creatorcontrib>MIAO, DONGMEI</creatorcontrib><creatorcontrib>ZHANG, CAIGUO</creatorcontrib><creatorcontrib>MICHELS, AARON W.</creatorcontrib><creatorcontrib>YU, LIPING</creatorcontrib><creatorcontrib>WENZLAU, JANET M.</creatorcontrib><title>186-OR: Novel Autoantibodies to Deamidated IA2 Extracellular Domain in Type 1 Diabetes</title><title>Diabetes (New York, N.Y.)</title><description>Background: Insulinoma antigen-2 (IA2) is a major self-antigen in T1D with post translational modification (PTM) of the extracellular domain (IA2ec) by deamidation eliciting T cell responses in T1D patients. Yet the autoantibodies (Abs) to these IA2ec PTM epitopes in T1D has not been studied.
Methods: IA2ec protein containing all the four T-cell responsive deamidated Q>E epitopes (aa 198-216, 467-482, 523-536 and 545-562) was produced. Sera from 269 new onset T1D children (median age= 12.6yrs) and 3age-matched healthy children were tested for Abs to IA2ecQ>E and wide type (WT) IA2ec with radiobinding assay (RBA) .
Results: The assay cut-offs were set at the 99th percentile for both IA2ecQ>E Ab and IA2ecWT Ab. In T1D children, positivity for IA2ecQ>E Ab was 60.6% (163/269) vs. IA2ecWT Ab 19.3% (52/269, P<0.0001) . In two subgroups of T1D patients who were positive (n=157) or negative (n=112) for current Abs to IA2 intra-cellular domain (IA2ic) , the positivity of IA2ecQ>E Ab were significantly higher than IA2ecWT Ab (Fig) , 58% (91/157) vs. 15.3% (24/157, P<0.0001) and 64.3% (72/112) vs. 25% (28/112, p<0.0001) . However, the positivity of IA2ec Ab did not differ between the patients with or without IA2ic Ab.
Conclusion: IA2ecQ>E Ab was detected in a large proportion of T1D patients, independent of the prototypical IA2ic Ab. IA2ecQ>E Ab is potentially a new novel predictive and diagnostic biomarker for T1D.</description><subject>Antigens</subject><subject>Autoantibodies</subject><subject>Autoantigens</subject><subject>Children</subject><subject>Diabetes</subject><subject>Diabetes mellitus (insulin dependent)</subject><subject>Epitopes</subject><subject>Insulinoma</subject><subject>Lymphocytes T</subject><subject>Neuroendocrine tumors</subject><issn>0012-1797</issn><issn>1939-327X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><recordid>eNotkE1LAzEQQIMoWKsn_0DAo6zmw91kvZW2aqG4UKp4C0l2Alu2TU2yYv-9KZUZmMO8mWEeQreUPDDOxWNrGCuorIpmdYZGtOZ1wZn4OkcjQmjuiFpcoqsYN4SQKscIfZ7oZ_zuf6DHkyF5vUud8W0HESePZ6C3XasTtHgxYXj-m4K20PdDrwOe-a3udjjn-rAHTPGs0wYSxGt04XQf4ea_jtHHy3w9fSuWzetiOlkWlpKKFWUFFByzDJxwFQhrSH7DGlNrYqgFyhjXJdPSSWqIMFY8aUEq56hs8wjhY3R32rsP_nuAmNTGD2GXTypWybKUdS1Zpu5PlA0-xgBO7UO31eGgKFFHceooTmUVqlnxP5hyX2g</recordid><startdate>20220601</startdate><enddate>20220601</enddate><creator>JIA, XIAOFAN</creator><creator>MIAO, DONGMEI</creator><creator>ZHANG, CAIGUO</creator><creator>MICHELS, AARON W.</creator><creator>YU, LIPING</creator><creator>WENZLAU, JANET M.</creator><general>American Diabetes Association</general><scope>AAYXX</scope><scope>CITATION</scope><scope>K9.</scope><scope>NAPCQ</scope></search><sort><creationdate>20220601</creationdate><title>186-OR: Novel Autoantibodies to Deamidated IA2 Extracellular Domain in Type 1 Diabetes</title><author>JIA, XIAOFAN ; MIAO, DONGMEI ; ZHANG, CAIGUO ; MICHELS, AARON W. ; YU, LIPING ; WENZLAU, JANET M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c1062-56e1ef2c2ef7f6e7cb0337cbb9a0b1ce1223a52a8f81b07bc74a706ff18def703</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Antigens</topic><topic>Autoantibodies</topic><topic>Autoantigens</topic><topic>Children</topic><topic>Diabetes</topic><topic>Diabetes mellitus (insulin dependent)</topic><topic>Epitopes</topic><topic>Insulinoma</topic><topic>Lymphocytes T</topic><topic>Neuroendocrine tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>JIA, XIAOFAN</creatorcontrib><creatorcontrib>MIAO, DONGMEI</creatorcontrib><creatorcontrib>ZHANG, CAIGUO</creatorcontrib><creatorcontrib>MICHELS, AARON W.</creatorcontrib><creatorcontrib>YU, LIPING</creatorcontrib><creatorcontrib>WENZLAU, JANET M.</creatorcontrib><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><jtitle>Diabetes (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>JIA, XIAOFAN</au><au>MIAO, DONGMEI</au><au>ZHANG, CAIGUO</au><au>MICHELS, AARON W.</au><au>YU, LIPING</au><au>WENZLAU, JANET M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>186-OR: Novel Autoantibodies to Deamidated IA2 Extracellular Domain in Type 1 Diabetes</atitle><jtitle>Diabetes (New York, N.Y.)</jtitle><date>2022-06-01</date><risdate>2022</risdate><volume>71</volume><issue>Supplement_1</issue><issn>0012-1797</issn><eissn>1939-327X</eissn><abstract>Background: Insulinoma antigen-2 (IA2) is a major self-antigen in T1D with post translational modification (PTM) of the extracellular domain (IA2ec) by deamidation eliciting T cell responses in T1D patients. Yet the autoantibodies (Abs) to these IA2ec PTM epitopes in T1D has not been studied.
Methods: IA2ec protein containing all the four T-cell responsive deamidated Q>E epitopes (aa 198-216, 467-482, 523-536 and 545-562) was produced. Sera from 269 new onset T1D children (median age= 12.6yrs) and 3age-matched healthy children were tested for Abs to IA2ecQ>E and wide type (WT) IA2ec with radiobinding assay (RBA) .
Results: The assay cut-offs were set at the 99th percentile for both IA2ecQ>E Ab and IA2ecWT Ab. In T1D children, positivity for IA2ecQ>E Ab was 60.6% (163/269) vs. IA2ecWT Ab 19.3% (52/269, P<0.0001) . In two subgroups of T1D patients who were positive (n=157) or negative (n=112) for current Abs to IA2 intra-cellular domain (IA2ic) , the positivity of IA2ecQ>E Ab were significantly higher than IA2ecWT Ab (Fig) , 58% (91/157) vs. 15.3% (24/157, P<0.0001) and 64.3% (72/112) vs. 25% (28/112, p<0.0001) . However, the positivity of IA2ec Ab did not differ between the patients with or without IA2ic Ab.
Conclusion: IA2ecQ>E Ab was detected in a large proportion of T1D patients, independent of the prototypical IA2ic Ab. IA2ecQ>E Ab is potentially a new novel predictive and diagnostic biomarker for T1D.</abstract><cop>New York</cop><pub>American Diabetes Association</pub><doi>10.2337/db22-186-OR</doi></addata></record> |
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| subjects | Antigens Autoantibodies Autoantigens Children Diabetes Diabetes mellitus (insulin dependent) Epitopes Insulinoma Lymphocytes T Neuroendocrine tumors |
| title | 186-OR: Novel Autoantibodies to Deamidated IA2 Extracellular Domain in Type 1 Diabetes |
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