Alterations of Global DNA Methylation and DNA Methyltransferase Expression in T and B Lymphocytes from Patients with Newly Diagnosed Autoimmune Thyroid Diseases After Treatment: A Follow-Up Study
Background: Dysregulated DNA methylation in lymphocytes has been linked to autoimmune disorders. The aims of this study were to identify global DNA methylation patterns in patients with autoimmune thyroid diseases and to observe methylation changes after treatment for these conditions. Methods: A cr...
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| Veröffentlicht in: | Thyroid (New York, N.Y.) N.Y.), 2018-03, Vol.28 (3), p.377-385 |
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| creator | Guo, Qingling Wu, Dan Yu, Huixin Bao, Jiandong Peng, Shiqiao Shan, Zhongyan Guan, Haixia Teng, Weiping |
| description | Background:
Dysregulated DNA methylation in lymphocytes has been linked to autoimmune disorders. The aims of this study were to identify global DNA methylation patterns in patients with autoimmune thyroid diseases and to observe methylation changes after treatment for these conditions.
Methods:
A cross-sectional study was conducted, including the following patients: 51 with newly diagnosed Graves' disease (GD), 28 with autoimmune hypothyroidism (AIT), 29 with positive thyroid autoantibodies, and 39 matched healthy volunteers. Forty GD patients treated with radioiodine or antithyroid drugs and 28 AIT patients treated with L-thyroxine were followed for three months. Serum free triiodothyronine, free thyroxine, thyrotropin, thyroid peroxidase antibodies, thyroglobulin antibodies, and thyrotropin receptor antibodies were assayed using electrochemiluminescent immunoassays. CD3
+
T and CD19
+
B cells were separated by flow cytometry for total DNA and RNA extraction. Global DNA methylation levels were determined by absorptiometry using a methylation quantification kit. DNA methyltransferase (DNMT) expression levels were detected by real-time polymerase chain reaction.
Results:
Hypomethylation and down-regulated DNMT1 expression in T and B lymphocytes were observed in the newly diagnosed GD patients. Neither the AIT patients nor the positive thyroid autoantibodies patients exhibited differences in their global DNA methylation status or DNMT mRNA levels compared with healthy controls. Antithyroid drugs restored global methylation and DNMT1 expression in both T and B lymphocytes, whereas radioiodine therapy affected only T cells. L-thyroxine replacement did not alter the methylation or DNMT expression levels in lymphocytes. The global methylation levels of B cells were negatively correlated with the serum thyroid peroxidase antibodies in patients with autoimmune thyroid diseases.
Conclusions:
Hyperthyroid patients with newly diagnosed GD had global hypomethylation and lower DNMT1 expression in T and B lymphocytes. The results provide the first demonstration that antithyroid drugs or radioiodine treatment restore global DNA methylation and DNMT1 expression with concurrent relief of hyperthyroidism. |
| doi_str_mv | 10.1089/thy.2017.0301 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1989571459</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1989571459</sourcerecordid><originalsourceid>FETCH-LOGICAL-c337t-91f17ca724525c87e0e4850eebe063e0d993aad5477b76318f1e3c2a33ed27d33</originalsourceid><addsrcrecordid>eNqFkU1v1DAQhi0EoqVw5IrmyCWLHa_jhFvoJ9JSkNieI28yYY0cO9iOtvl9_LE63YK4cfJo_PjxaF5C3jK6YrSsPsT9vMopkyvKKXtGTpkQMquolM9TTQXNZC6KE_IqhJ-UsqKU_CU5ySvOi5zTU_K7NhG9itrZAK6Ha-N2ysDFbQ1fMLnN4xUo2_3Ti17Z0KdnAeHyfvQYwgJpC9tH8hNs5mHcu3aOGKD3boBvyYM2BjjouIdbPJgZLrT6YV3ADuopOj0Mk0XY7mfvdPpNB0z-AHWfBoStRxWHZPgINVw5Y9whuxvhe5y6-TV50SsT8M3TeUburi635zfZ5uv15_N6k7Wcy5hVrGeyVTJfi1y0pUSK61JQxB3SgiPtqoor1Ym1lDtZcFb2DHmbK86xy2XH-Rl5f_SO3v2aMMRm0KFFY5RFN4WGVWUlJFuLKqHZEW29C8Fj34xeD8rPDaPNkluT9tgsuTVLbol_96SedgN2f-k_QSWAH4Glraw1Oo3t43-0D20ap-8</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1989571459</pqid></control><display><type>article</type><title>Alterations of Global DNA Methylation and DNA Methyltransferase Expression in T and B Lymphocytes from Patients with Newly Diagnosed Autoimmune Thyroid Diseases After Treatment: A Follow-Up Study</title><source>MEDLINE</source><source>Alma/SFX Local Collection</source><creator>Guo, Qingling ; Wu, Dan ; Yu, Huixin ; Bao, Jiandong ; Peng, Shiqiao ; Shan, Zhongyan ; Guan, Haixia ; Teng, Weiping</creator><creatorcontrib>Guo, Qingling ; Wu, Dan ; Yu, Huixin ; Bao, Jiandong ; Peng, Shiqiao ; Shan, Zhongyan ; Guan, Haixia ; Teng, Weiping</creatorcontrib><description>Background:
Dysregulated DNA methylation in lymphocytes has been linked to autoimmune disorders. The aims of this study were to identify global DNA methylation patterns in patients with autoimmune thyroid diseases and to observe methylation changes after treatment for these conditions.
Methods:
A cross-sectional study was conducted, including the following patients: 51 with newly diagnosed Graves' disease (GD), 28 with autoimmune hypothyroidism (AIT), 29 with positive thyroid autoantibodies, and 39 matched healthy volunteers. Forty GD patients treated with radioiodine or antithyroid drugs and 28 AIT patients treated with L-thyroxine were followed for three months. Serum free triiodothyronine, free thyroxine, thyrotropin, thyroid peroxidase antibodies, thyroglobulin antibodies, and thyrotropin receptor antibodies were assayed using electrochemiluminescent immunoassays. CD3
+
T and CD19
+
B cells were separated by flow cytometry for total DNA and RNA extraction. Global DNA methylation levels were determined by absorptiometry using a methylation quantification kit. DNA methyltransferase (DNMT) expression levels were detected by real-time polymerase chain reaction.
Results:
Hypomethylation and down-regulated DNMT1 expression in T and B lymphocytes were observed in the newly diagnosed GD patients. Neither the AIT patients nor the positive thyroid autoantibodies patients exhibited differences in their global DNA methylation status or DNMT mRNA levels compared with healthy controls. Antithyroid drugs restored global methylation and DNMT1 expression in both T and B lymphocytes, whereas radioiodine therapy affected only T cells. L-thyroxine replacement did not alter the methylation or DNMT expression levels in lymphocytes. The global methylation levels of B cells were negatively correlated with the serum thyroid peroxidase antibodies in patients with autoimmune thyroid diseases.
Conclusions:
Hyperthyroid patients with newly diagnosed GD had global hypomethylation and lower DNMT1 expression in T and B lymphocytes. The results provide the first demonstration that antithyroid drugs or radioiodine treatment restore global DNA methylation and DNMT1 expression with concurrent relief of hyperthyroidism.</description><identifier>ISSN: 1050-7256</identifier><identifier>EISSN: 1557-9077</identifier><identifier>DOI: 10.1089/thy.2017.0301</identifier><identifier>PMID: 29336230</identifier><language>eng</language><publisher>United States: Mary Ann Liebert, Inc</publisher><subject>Adult ; B-Lymphocytes - metabolism ; Cross-Sectional Studies ; DNA (Cytosine-5-)-Methyltransferase 1 - genetics ; DNA (Cytosine-5-)-Methyltransferase 1 - metabolism ; DNA Methylation ; Female ; Graves Disease - drug therapy ; Graves Disease - metabolism ; Graves Disease - radiotherapy ; Hashimoto Disease - drug therapy ; Hashimoto Disease - metabolism ; Humans ; Hypothyroidism - drug therapy ; Hypothyroidism - metabolism ; Immunology, Autoimmunity, and Graves' Ophthalmopathy ; Iodine Radioisotopes - therapeutic use ; Male ; Methimazole - therapeutic use ; Middle Aged ; Propylthiouracil - therapeutic use ; T-Lymphocytes - metabolism ; Thyroiditis, Autoimmune - drug therapy ; Thyroiditis, Autoimmune - metabolism ; Thyroxine - blood ; Thyroxine - therapeutic use ; Triiodothyronine - blood</subject><ispartof>Thyroid (New York, N.Y.), 2018-03, Vol.28 (3), p.377-385</ispartof><rights>2018, Mary Ann Liebert, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c337t-91f17ca724525c87e0e4850eebe063e0d993aad5477b76318f1e3c2a33ed27d33</citedby><cites>FETCH-LOGICAL-c337t-91f17ca724525c87e0e4850eebe063e0d993aad5477b76318f1e3c2a33ed27d33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,778,782,27911,27912</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29336230$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Guo, Qingling</creatorcontrib><creatorcontrib>Wu, Dan</creatorcontrib><creatorcontrib>Yu, Huixin</creatorcontrib><creatorcontrib>Bao, Jiandong</creatorcontrib><creatorcontrib>Peng, Shiqiao</creatorcontrib><creatorcontrib>Shan, Zhongyan</creatorcontrib><creatorcontrib>Guan, Haixia</creatorcontrib><creatorcontrib>Teng, Weiping</creatorcontrib><title>Alterations of Global DNA Methylation and DNA Methyltransferase Expression in T and B Lymphocytes from Patients with Newly Diagnosed Autoimmune Thyroid Diseases After Treatment: A Follow-Up Study</title><title>Thyroid (New York, N.Y.)</title><addtitle>Thyroid</addtitle><description>Background:
Dysregulated DNA methylation in lymphocytes has been linked to autoimmune disorders. The aims of this study were to identify global DNA methylation patterns in patients with autoimmune thyroid diseases and to observe methylation changes after treatment for these conditions.
Methods:
A cross-sectional study was conducted, including the following patients: 51 with newly diagnosed Graves' disease (GD), 28 with autoimmune hypothyroidism (AIT), 29 with positive thyroid autoantibodies, and 39 matched healthy volunteers. Forty GD patients treated with radioiodine or antithyroid drugs and 28 AIT patients treated with L-thyroxine were followed for three months. Serum free triiodothyronine, free thyroxine, thyrotropin, thyroid peroxidase antibodies, thyroglobulin antibodies, and thyrotropin receptor antibodies were assayed using electrochemiluminescent immunoassays. CD3
+
T and CD19
+
B cells were separated by flow cytometry for total DNA and RNA extraction. Global DNA methylation levels were determined by absorptiometry using a methylation quantification kit. DNA methyltransferase (DNMT) expression levels were detected by real-time polymerase chain reaction.
Results:
Hypomethylation and down-regulated DNMT1 expression in T and B lymphocytes were observed in the newly diagnosed GD patients. Neither the AIT patients nor the positive thyroid autoantibodies patients exhibited differences in their global DNA methylation status or DNMT mRNA levels compared with healthy controls. Antithyroid drugs restored global methylation and DNMT1 expression in both T and B lymphocytes, whereas radioiodine therapy affected only T cells. L-thyroxine replacement did not alter the methylation or DNMT expression levels in lymphocytes. The global methylation levels of B cells were negatively correlated with the serum thyroid peroxidase antibodies in patients with autoimmune thyroid diseases.
Conclusions:
Hyperthyroid patients with newly diagnosed GD had global hypomethylation and lower DNMT1 expression in T and B lymphocytes. The results provide the first demonstration that antithyroid drugs or radioiodine treatment restore global DNA methylation and DNMT1 expression with concurrent relief of hyperthyroidism.</description><subject>Adult</subject><subject>B-Lymphocytes - metabolism</subject><subject>Cross-Sectional Studies</subject><subject>DNA (Cytosine-5-)-Methyltransferase 1 - genetics</subject><subject>DNA (Cytosine-5-)-Methyltransferase 1 - metabolism</subject><subject>DNA Methylation</subject><subject>Female</subject><subject>Graves Disease - drug therapy</subject><subject>Graves Disease - metabolism</subject><subject>Graves Disease - radiotherapy</subject><subject>Hashimoto Disease - drug therapy</subject><subject>Hashimoto Disease - metabolism</subject><subject>Humans</subject><subject>Hypothyroidism - drug therapy</subject><subject>Hypothyroidism - metabolism</subject><subject>Immunology, Autoimmunity, and Graves' Ophthalmopathy</subject><subject>Iodine Radioisotopes - therapeutic use</subject><subject>Male</subject><subject>Methimazole - therapeutic use</subject><subject>Middle Aged</subject><subject>Propylthiouracil - therapeutic use</subject><subject>T-Lymphocytes - metabolism</subject><subject>Thyroiditis, Autoimmune - drug therapy</subject><subject>Thyroiditis, Autoimmune - metabolism</subject><subject>Thyroxine - blood</subject><subject>Thyroxine - therapeutic use</subject><subject>Triiodothyronine - blood</subject><issn>1050-7256</issn><issn>1557-9077</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1v1DAQhi0EoqVw5IrmyCWLHa_jhFvoJ9JSkNieI28yYY0cO9iOtvl9_LE63YK4cfJo_PjxaF5C3jK6YrSsPsT9vMopkyvKKXtGTpkQMquolM9TTQXNZC6KE_IqhJ-UsqKU_CU5ySvOi5zTU_K7NhG9itrZAK6Ha-N2ysDFbQ1fMLnN4xUo2_3Ti17Z0KdnAeHyfvQYwgJpC9tH8hNs5mHcu3aOGKD3boBvyYM2BjjouIdbPJgZLrT6YV3ADuopOj0Mk0XY7mfvdPpNB0z-AHWfBoStRxWHZPgINVw5Y9whuxvhe5y6-TV50SsT8M3TeUburi635zfZ5uv15_N6k7Wcy5hVrGeyVTJfi1y0pUSK61JQxB3SgiPtqoor1Ym1lDtZcFb2DHmbK86xy2XH-Rl5f_SO3v2aMMRm0KFFY5RFN4WGVWUlJFuLKqHZEW29C8Fj34xeD8rPDaPNkluT9tgsuTVLbol_96SedgN2f-k_QSWAH4Glraw1Oo3t43-0D20ap-8</recordid><startdate>20180301</startdate><enddate>20180301</enddate><creator>Guo, Qingling</creator><creator>Wu, Dan</creator><creator>Yu, Huixin</creator><creator>Bao, Jiandong</creator><creator>Peng, Shiqiao</creator><creator>Shan, Zhongyan</creator><creator>Guan, Haixia</creator><creator>Teng, Weiping</creator><general>Mary Ann Liebert, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20180301</creationdate><title>Alterations of Global DNA Methylation and DNA Methyltransferase Expression in T and B Lymphocytes from Patients with Newly Diagnosed Autoimmune Thyroid Diseases After Treatment: A Follow-Up Study</title><author>Guo, Qingling ; Wu, Dan ; Yu, Huixin ; Bao, Jiandong ; Peng, Shiqiao ; Shan, Zhongyan ; Guan, Haixia ; Teng, Weiping</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c337t-91f17ca724525c87e0e4850eebe063e0d993aad5477b76318f1e3c2a33ed27d33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Adult</topic><topic>B-Lymphocytes - metabolism</topic><topic>Cross-Sectional Studies</topic><topic>DNA (Cytosine-5-)-Methyltransferase 1 - genetics</topic><topic>DNA (Cytosine-5-)-Methyltransferase 1 - metabolism</topic><topic>DNA Methylation</topic><topic>Female</topic><topic>Graves Disease - drug therapy</topic><topic>Graves Disease - metabolism</topic><topic>Graves Disease - radiotherapy</topic><topic>Hashimoto Disease - drug therapy</topic><topic>Hashimoto Disease - metabolism</topic><topic>Humans</topic><topic>Hypothyroidism - drug therapy</topic><topic>Hypothyroidism - metabolism</topic><topic>Immunology, Autoimmunity, and Graves' Ophthalmopathy</topic><topic>Iodine Radioisotopes - therapeutic use</topic><topic>Male</topic><topic>Methimazole - therapeutic use</topic><topic>Middle Aged</topic><topic>Propylthiouracil - therapeutic use</topic><topic>T-Lymphocytes - metabolism</topic><topic>Thyroiditis, Autoimmune - drug therapy</topic><topic>Thyroiditis, Autoimmune - metabolism</topic><topic>Thyroxine - blood</topic><topic>Thyroxine - therapeutic use</topic><topic>Triiodothyronine - blood</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Guo, Qingling</creatorcontrib><creatorcontrib>Wu, Dan</creatorcontrib><creatorcontrib>Yu, Huixin</creatorcontrib><creatorcontrib>Bao, Jiandong</creatorcontrib><creatorcontrib>Peng, Shiqiao</creatorcontrib><creatorcontrib>Shan, Zhongyan</creatorcontrib><creatorcontrib>Guan, Haixia</creatorcontrib><creatorcontrib>Teng, Weiping</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Thyroid (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Guo, Qingling</au><au>Wu, Dan</au><au>Yu, Huixin</au><au>Bao, Jiandong</au><au>Peng, Shiqiao</au><au>Shan, Zhongyan</au><au>Guan, Haixia</au><au>Teng, Weiping</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Alterations of Global DNA Methylation and DNA Methyltransferase Expression in T and B Lymphocytes from Patients with Newly Diagnosed Autoimmune Thyroid Diseases After Treatment: A Follow-Up Study</atitle><jtitle>Thyroid (New York, N.Y.)</jtitle><addtitle>Thyroid</addtitle><date>2018-03-01</date><risdate>2018</risdate><volume>28</volume><issue>3</issue><spage>377</spage><epage>385</epage><pages>377-385</pages><issn>1050-7256</issn><eissn>1557-9077</eissn><abstract>Background:
Dysregulated DNA methylation in lymphocytes has been linked to autoimmune disorders. The aims of this study were to identify global DNA methylation patterns in patients with autoimmune thyroid diseases and to observe methylation changes after treatment for these conditions.
Methods:
A cross-sectional study was conducted, including the following patients: 51 with newly diagnosed Graves' disease (GD), 28 with autoimmune hypothyroidism (AIT), 29 with positive thyroid autoantibodies, and 39 matched healthy volunteers. Forty GD patients treated with radioiodine or antithyroid drugs and 28 AIT patients treated with L-thyroxine were followed for three months. Serum free triiodothyronine, free thyroxine, thyrotropin, thyroid peroxidase antibodies, thyroglobulin antibodies, and thyrotropin receptor antibodies were assayed using electrochemiluminescent immunoassays. CD3
+
T and CD19
+
B cells were separated by flow cytometry for total DNA and RNA extraction. Global DNA methylation levels were determined by absorptiometry using a methylation quantification kit. DNA methyltransferase (DNMT) expression levels were detected by real-time polymerase chain reaction.
Results:
Hypomethylation and down-regulated DNMT1 expression in T and B lymphocytes were observed in the newly diagnosed GD patients. Neither the AIT patients nor the positive thyroid autoantibodies patients exhibited differences in their global DNA methylation status or DNMT mRNA levels compared with healthy controls. Antithyroid drugs restored global methylation and DNMT1 expression in both T and B lymphocytes, whereas radioiodine therapy affected only T cells. L-thyroxine replacement did not alter the methylation or DNMT expression levels in lymphocytes. The global methylation levels of B cells were negatively correlated with the serum thyroid peroxidase antibodies in patients with autoimmune thyroid diseases.
Conclusions:
Hyperthyroid patients with newly diagnosed GD had global hypomethylation and lower DNMT1 expression in T and B lymphocytes. The results provide the first demonstration that antithyroid drugs or radioiodine treatment restore global DNA methylation and DNMT1 expression with concurrent relief of hyperthyroidism.</abstract><cop>United States</cop><pub>Mary Ann Liebert, Inc</pub><pmid>29336230</pmid><doi>10.1089/thy.2017.0301</doi><tpages>9</tpages></addata></record> |
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| ispartof | Thyroid (New York, N.Y.), 2018-03, Vol.28 (3), p.377-385 |
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| language | eng |
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| subjects | Adult B-Lymphocytes - metabolism Cross-Sectional Studies DNA (Cytosine-5-)-Methyltransferase 1 - genetics DNA (Cytosine-5-)-Methyltransferase 1 - metabolism DNA Methylation Female Graves Disease - drug therapy Graves Disease - metabolism Graves Disease - radiotherapy Hashimoto Disease - drug therapy Hashimoto Disease - metabolism Humans Hypothyroidism - drug therapy Hypothyroidism - metabolism Immunology, Autoimmunity, and Graves' Ophthalmopathy Iodine Radioisotopes - therapeutic use Male Methimazole - therapeutic use Middle Aged Propylthiouracil - therapeutic use T-Lymphocytes - metabolism Thyroiditis, Autoimmune - drug therapy Thyroiditis, Autoimmune - metabolism Thyroxine - blood Thyroxine - therapeutic use Triiodothyronine - blood |
| title | Alterations of Global DNA Methylation and DNA Methyltransferase Expression in T and B Lymphocytes from Patients with Newly Diagnosed Autoimmune Thyroid Diseases After Treatment: A Follow-Up Study |
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