Estimation of serum TSH receptor autoantibody concentration and affinity
We have used the human monoclonal TSH receptor (TSHR) autoantibody (M22) as a labeled ligand in competition with individual patient TSHR autoantibodies (TRAb) to estimate their serum concentrations and affinities. TSHR coated tubes, (125)I-labeled M22 IgG and Fab, and patient sera IgG and Fab were u...
Uložené v:
| Vydané v: | Thyroid (New York, N.Y.) Ročník 16; číslo 11; s. 1077 |
|---|---|
| Hlavní autori: | , , , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | English |
| Vydavateľské údaje: |
United States
01.11.2006
|
| Predmet: | |
| ISSN: | 1050-7256 |
| On-line prístup: | Zistit podrobnosti o prístupe |
| Tagy: |
Pridať tag
Žiadne tagy, Buďte prvý, kto otaguje tento záznam!
|
| Abstract | We have used the human monoclonal TSH receptor (TSHR) autoantibody (M22) as a labeled ligand in competition with individual patient TSHR autoantibodies (TRAb) to estimate their serum concentrations and affinities. TSHR coated tubes, (125)I-labeled M22 IgG and Fab, and patient sera IgG and Fab were used in these studies. In 15 patients with Graves' disease, TRAb concentrations ranged from 50 to 500 ng/mL of serum (5- 60 parts per million of total serum IgG) and TRAb IgG affinities from 3.0 +/- 1.0-6.7 +/- 1.54-10(10) L/mol (mean +/- SD; n=3). Fab fragment affinities were similar to those of intact IgG. Serum TRAb with blocking (TSH antagonist; 4 patients) activity had similar affinities (3.0 +/- 0.25-7.2 +/- 2.2-10(10) L/mol) to TRAb IgG from patients with Graves' disease, but blocking TRAb concentrations were higher (1.7 - 27 mg/mL of serum). The concentrations of TRAb that we observed in the sera of the 15 Graves' patient (0.33 - 3.3 nmol/L) can be compared with that of circulating TSH. In particular, a serum TSH concentration of 100mU/L (0.7 nmol/L) is in the same range as the concentrations of TRAb we observed. Such a TSH concentration (similar to that observed after injection of 0.9 mg of recombinant human TSH) would be expected to cause a similar degree of thyrotoxicosis as seen in Graves' disease. Consequently, the thyroid-stimulating potencies (i.e., activity per mol) of patient serum TRAb and human TSH appear to be of a similar magnitude in vivo as well as in vitro. Overall, our results indicate that serum TRAb affinities are high and show only limited variations between different sera whereas concentrations of the autoantibodies vary widely. |
|---|---|
| AbstractList | We have used the human monoclonal TSH receptor (TSHR) autoantibody (M22) as a labeled ligand in competition with individual patient TSHR autoantibodies (TRAb) to estimate their serum concentrations and affinities. TSHR coated tubes, (125)I-labeled M22 IgG and Fab, and patient sera IgG and Fab were used in these studies. In 15 patients with Graves' disease, TRAb concentrations ranged from 50 to 500 ng/mL of serum (5- 60 parts per million of total serum IgG) and TRAb IgG affinities from 3.0 +/- 1.0-6.7 +/- 1.54-10(10) L/mol (mean +/- SD; n=3). Fab fragment affinities were similar to those of intact IgG. Serum TRAb with blocking (TSH antagonist; 4 patients) activity had similar affinities (3.0 +/- 0.25-7.2 +/- 2.2-10(10) L/mol) to TRAb IgG from patients with Graves' disease, but blocking TRAb concentrations were higher (1.7 - 27 mg/mL of serum). The concentrations of TRAb that we observed in the sera of the 15 Graves' patient (0.33 - 3.3 nmol/L) can be compared with that of circulating TSH. In particular, a serum TSH concentration of 100mU/L (0.7 nmol/L) is in the same range as the concentrations of TRAb we observed. Such a TSH concentration (similar to that observed after injection of 0.9 mg of recombinant human TSH) would be expected to cause a similar degree of thyrotoxicosis as seen in Graves' disease. Consequently, the thyroid-stimulating potencies (i.e., activity per mol) of patient serum TRAb and human TSH appear to be of a similar magnitude in vivo as well as in vitro. Overall, our results indicate that serum TRAb affinities are high and show only limited variations between different sera whereas concentrations of the autoantibodies vary widely.We have used the human monoclonal TSH receptor (TSHR) autoantibody (M22) as a labeled ligand in competition with individual patient TSHR autoantibodies (TRAb) to estimate their serum concentrations and affinities. TSHR coated tubes, (125)I-labeled M22 IgG and Fab, and patient sera IgG and Fab were used in these studies. In 15 patients with Graves' disease, TRAb concentrations ranged from 50 to 500 ng/mL of serum (5- 60 parts per million of total serum IgG) and TRAb IgG affinities from 3.0 +/- 1.0-6.7 +/- 1.54-10(10) L/mol (mean +/- SD; n=3). Fab fragment affinities were similar to those of intact IgG. Serum TRAb with blocking (TSH antagonist; 4 patients) activity had similar affinities (3.0 +/- 0.25-7.2 +/- 2.2-10(10) L/mol) to TRAb IgG from patients with Graves' disease, but blocking TRAb concentrations were higher (1.7 - 27 mg/mL of serum). The concentrations of TRAb that we observed in the sera of the 15 Graves' patient (0.33 - 3.3 nmol/L) can be compared with that of circulating TSH. In particular, a serum TSH concentration of 100mU/L (0.7 nmol/L) is in the same range as the concentrations of TRAb we observed. Such a TSH concentration (similar to that observed after injection of 0.9 mg of recombinant human TSH) would be expected to cause a similar degree of thyrotoxicosis as seen in Graves' disease. Consequently, the thyroid-stimulating potencies (i.e., activity per mol) of patient serum TRAb and human TSH appear to be of a similar magnitude in vivo as well as in vitro. Overall, our results indicate that serum TRAb affinities are high and show only limited variations between different sera whereas concentrations of the autoantibodies vary widely. We have used the human monoclonal TSH receptor (TSHR) autoantibody (M22) as a labeled ligand in competition with individual patient TSHR autoantibodies (TRAb) to estimate their serum concentrations and affinities. TSHR coated tubes, (125)I-labeled M22 IgG and Fab, and patient sera IgG and Fab were used in these studies. In 15 patients with Graves' disease, TRAb concentrations ranged from 50 to 500 ng/mL of serum (5- 60 parts per million of total serum IgG) and TRAb IgG affinities from 3.0 +/- 1.0-6.7 +/- 1.54-10(10) L/mol (mean +/- SD; n=3). Fab fragment affinities were similar to those of intact IgG. Serum TRAb with blocking (TSH antagonist; 4 patients) activity had similar affinities (3.0 +/- 0.25-7.2 +/- 2.2-10(10) L/mol) to TRAb IgG from patients with Graves' disease, but blocking TRAb concentrations were higher (1.7 - 27 mg/mL of serum). The concentrations of TRAb that we observed in the sera of the 15 Graves' patient (0.33 - 3.3 nmol/L) can be compared with that of circulating TSH. In particular, a serum TSH concentration of 100mU/L (0.7 nmol/L) is in the same range as the concentrations of TRAb we observed. Such a TSH concentration (similar to that observed after injection of 0.9 mg of recombinant human TSH) would be expected to cause a similar degree of thyrotoxicosis as seen in Graves' disease. Consequently, the thyroid-stimulating potencies (i.e., activity per mol) of patient serum TRAb and human TSH appear to be of a similar magnitude in vivo as well as in vitro. Overall, our results indicate that serum TRAb affinities are high and show only limited variations between different sera whereas concentrations of the autoantibodies vary widely. |
| Author | Furmaniak, Jadwiga Barrett, Carol Nakatake, Nobuhiro Betterle, Corrado Presotto, Fabio Smith, Bernard Rees Sanders, Jane Burne, Peter Pra, Chiara Dal Richards, Tonya |
| Author_xml | – sequence: 1 givenname: Nobuhiro surname: Nakatake fullname: Nakatake, Nobuhiro organization: FIRS Laboratories, RSR Ltd, Llanishen, Cardiff, United Kingdom – sequence: 2 givenname: Jane surname: Sanders fullname: Sanders, Jane – sequence: 3 givenname: Tonya surname: Richards fullname: Richards, Tonya – sequence: 4 givenname: Peter surname: Burne fullname: Burne, Peter – sequence: 5 givenname: Carol surname: Barrett fullname: Barrett, Carol – sequence: 6 givenname: Chiara Dal surname: Pra fullname: Pra, Chiara Dal – sequence: 7 givenname: Fabio surname: Presotto fullname: Presotto, Fabio – sequence: 8 givenname: Corrado surname: Betterle fullname: Betterle, Corrado – sequence: 9 givenname: Jadwiga surname: Furmaniak fullname: Furmaniak, Jadwiga – sequence: 10 givenname: Bernard Rees surname: Smith fullname: Smith, Bernard Rees |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/17123333$$D View this record in MEDLINE/PubMed |
| BookMark | eNo1TztrwzAY1JDSPNq9U9HUzak--SFpLCGtC4EOTWcjy5-oSyylkjz439eQ9Dg4OO4Obk0Wzjsk5AHYFphUz-l72nLGqi3MZEIsyApYyTLBy2pJ1jH-MAaVFPktWYIAns9YkXofUz_o1HtHvaURwzjQ42dNAxo8Jx-oHpPXLvWt7yZqvDPoUrgUtOuotrZ3fZruyI3Vp4j3V92Qr9f9cVdnh4-3993LITNFwVJmFcqyMsIYhpUCprhEVaDoRKe4bS2UVishZ8uq3BghC1ClVFKD1hyA8w15uuyeg_8dMaZm6KPB00k79GNsKglC8aKcg4_X4NgO2DXnMP8MU_P_nf8Bp6JcAg |
| CitedBy_id | crossref_primary_10_1016_j_cca_2008_02_005 crossref_primary_10_4158_EP_15_1_56 crossref_primary_10_1371_journal_pone_0192615 crossref_primary_10_3389_fimmu_2017_00603 crossref_primary_10_1111_cen_13908 crossref_primary_10_1089_thy_2007_0239 crossref_primary_10_1177_10507256251359557 crossref_primary_10_1586_eci_11_56 crossref_primary_10_1055_s_0035_1559648 crossref_primary_10_1016_j_ajog_2019_02_058 crossref_primary_10_1111_j_1365_2265_2010_03831_x crossref_primary_10_3390_jcm9061919 crossref_primary_10_2217_17520363_2_6_567 crossref_primary_10_1089_thy_2007_0327 crossref_primary_10_1515_cclm_2022_0162 crossref_primary_10_1210_jc_2008_2134 crossref_primary_10_1515_CCLM_2009_245 crossref_primary_10_3389_fphar_2023_1291856 crossref_primary_10_1089_thy_2012_0374 crossref_primary_10_1089_thy_2007_0034 crossref_primary_10_1016_j_ijbiomac_2017_10_133 crossref_primary_10_1089_hyb_2008_0045 crossref_primary_10_5937_jomb0_34718 crossref_primary_10_1007_s13317_011_0025_9 crossref_primary_10_1186_s13317_019_0121_9 |
| ContentType | Journal Article |
| DBID | CGR CUY CVF ECM EIF NPM 7X8 |
| DOI | 10.1089/thy.2006.16.1077 |
| DatabaseName | Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed MEDLINE - Academic |
| DatabaseTitle | MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) MEDLINE - Academic |
| DatabaseTitleList | MEDLINE - Academic MEDLINE |
| Database_xml | – sequence: 1 dbid: NPM name: PubMed url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: 7X8 name: MEDLINE - Academic url: https://search.proquest.com/medline sourceTypes: Aggregation Database |
| DeliveryMethod | no_fulltext_linktorsrc |
| Discipline | Medicine |
| ExternalDocumentID | 17123333 |
| Genre | Research Support, Non-U.S. Gov't Journal Article |
| GroupedDBID | --- 0R~ 1-M 123 29Q 34G 39C 4.4 53G 5RE AAQQT ABBKN ABJNI ABOCM ACGFO ACGFS ADBBV AEGXH AENEX AIAGR ALMA_UNASSIGNED_HOLDINGS BNQNF CAG CGR COF CS3 CUY CVF DU5 EBS ECM EIF EJD EMOBN F5P IAO IER IHR IM4 INH INR ITC MV1 NPM NQHIM O9- P2P RIG RML RMSOB UDS UE5 7X8 SCNPE |
| ID | FETCH-LOGICAL-c440t-f9e856c7cc0e6910928e94e7d7d92fbf15fa97894ef93cc784195898a1aa21122 |
| IEDL.DBID | 7X8 |
| ISICitedReferencesCount | 32 |
| ISICitedReferencesURI | http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=000242557600002&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| ISSN | 1050-7256 |
| IngestDate | Thu Oct 02 04:15:01 EDT 2025 Sat Sep 28 07:51:40 EDT 2024 |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 11 |
| Language | English |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-c440t-f9e856c7cc0e6910928e94e7d7d92fbf15fa97894ef93cc784195898a1aa21122 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| PMID | 17123333 |
| PQID | 68179245 |
| PQPubID | 23479 |
| ParticipantIDs | proquest_miscellaneous_68179245 pubmed_primary_17123333 |
| PublicationCentury | 2000 |
| PublicationDate | 2006-Nov 20061101 |
| PublicationDateYYYYMMDD | 2006-11-01 |
| PublicationDate_xml | – month: 11 year: 2006 text: 2006-Nov |
| PublicationDecade | 2000 |
| PublicationPlace | United States |
| PublicationPlace_xml | – name: United States |
| PublicationTitle | Thyroid (New York, N.Y.) |
| PublicationTitleAlternate | Thyroid |
| PublicationYear | 2006 |
| SSID | ssj0016873 |
| Score | 1.9734291 |
| Snippet | We have used the human monoclonal TSH receptor (TSHR) autoantibody (M22) as a labeled ligand in competition with individual patient TSHR autoantibodies (TRAb)... |
| SourceID | proquest pubmed |
| SourceType | Aggregation Database Index Database |
| StartPage | 1077 |
| SubjectTerms | Antibodies, Monoclonal - pharmacology Antibody Affinity Autoantibodies - blood Binding, Competitive - immunology Chromatography, Affinity Graves Disease - immunology Humans Immunoglobulin Fab Fragments - blood Immunoglobulin Fab Fragments - pharmacology Immunoglobulin G - blood Immunoglobulin G - pharmacology Immunoglobulins, Thyroid-Stimulating Iodine Radioisotopes Receptors, Thyrotropin - immunology Receptors, Thyrotropin - metabolism Thyrotoxicosis - immunology |
| Title | Estimation of serum TSH receptor autoantibody concentration and affinity |
| URI | https://www.ncbi.nlm.nih.gov/pubmed/17123333 https://www.proquest.com/docview/68179245 |
| Volume | 16 |
| WOSCitedRecordID | wos000242557600002&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| hasFullText | |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV1LSwMxEB6qFfHi-1GfOXgN7iPZJCCISEsvLQUr9LZkswn04G61rdB_72QfeBIPLsseArsswzevfDMZgHvFrcxQbRC8KqbM5poqa0KaMWYQH86oSFfDJsR4LGczNenAY9sL48sqW5tYGeq8NH6P_CGRCJ2I8afFB_Uzozy32gzQ2IJujIGML-gSsx8OIZGiLq_nARXo2RuSMpDqAWVQ8xAh3oEQv4eXlZsZHPzvBw9hvwkvyXONhyPo2OIYdkcNgX4Cwz6qdN2tSEpHEH_rdzJ9HRI0fHaB-TfR61WJ0p5nZb4hxjc1Fs3JukQXOdHOzdEKbE7hbdCfvgxpM0yBGsaCFXXKSp4YYUxgE4wRVCStYlbkIleRy1zIncaMEpecio3xdKTiUkkdao1JYhSdwXZRFvYCSCyklpqxzFrHYsc1xlB-fgd-K4ytSnpw10ooRbB6BkIXtlwv01ZGPTivhZwu6jM10lCgC8Xr8s93r2Cv2gap-gGvoetQTe0N7Jiv1Xz5eVthAJ_jyegbgIC8KQ |
| linkProvider | ProQuest |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Estimation+of+serum+TSH+receptor+autoantibody+concentration+and+affinity&rft.jtitle=Thyroid+%28New+York%2C+N.Y.%29&rft.au=Nakatake%2C+Nobuhiro&rft.au=Sanders%2C+Jane&rft.au=Richards%2C+Tonya&rft.au=Burne%2C+Peter&rft.date=2006-11-01&rft.issn=1050-7256&rft.volume=16&rft.issue=11&rft.spage=1077&rft_id=info:doi/10.1089%2Fthy.2006.16.1077&rft.externalDBID=NO_FULL_TEXT |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1050-7256&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1050-7256&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1050-7256&client=summon |