Development of a novel diagnostic assay for insulin receptor autoantibodies based on a patient with autoimmune hypoglycaemia
Differential diagnosis of hypoglycaemia can at times be challenging for patients who appear to be well. Here we identify the case of a 66-year-old Chinese man presenting with recurrent episodes of fasting hypoglycaemia and confusion without any other manifestations. He had no personal or family hist...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-10-01
|
| Series: | Frontiers in Endocrinology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2022.1029297/full |
| _version_ | 1798030565746671616 |
|---|---|
| author | Leiluo Geng Leiluo Geng Cheuk-Lik Wong Boya Liao Ying Lin Ying Lin Hao Han Hao Han Karen S. L. Lam Karen S. L. Lam Aimin Xu Aimin Xu Aimin Xu Chi-Ho Lee Chi-Ho Lee Vicki H. K. Tam |
| author_facet | Leiluo Geng Leiluo Geng Cheuk-Lik Wong Boya Liao Ying Lin Ying Lin Hao Han Hao Han Karen S. L. Lam Karen S. L. Lam Aimin Xu Aimin Xu Aimin Xu Chi-Ho Lee Chi-Ho Lee Vicki H. K. Tam |
| author_sort | Leiluo Geng |
| collection | DOAJ |
| description | Differential diagnosis of hypoglycaemia can at times be challenging for patients who appear to be well. Here we identify the case of a 66-year-old Chinese man presenting with recurrent episodes of fasting hypoglycaemia and confusion without any other manifestations. He had no personal or family history of diabetes, nor was he on any hypoglycaemic drugs. The fasting insulin levels were elevated while the C-peptide and pro-insulin levels were slightly low or normal. Antibodies against insulin were negative and levels of insulin-like growth factors were normal. A series of imaging diagnosis excluded the presence of insulinoma or ectopic insulin-secreting neuroendocrine tumor. Ultimately, insulin receptor autoantibodies (IRAb) were detected by both immunoprecipitation assay and enzyme-linked immunosorbent assay (ELISA) developed in house. In a cell study, the immunoglobulins isolated from this patient exerted insulin-like effects on stimulation of post-insulin receptor signaling and glucose uptake as well as inhibited 125I-insulin binding with insulin receptors. Collectively, this patient was diagnosed with IRAb-induced autoimmune hypoglycaemia. Although this patient had no obvious immune disorders, several autoantibodies were identified in his plasma samples, suggesting the patient might have mild aberrant autoimmunity and therefore generated IRAb. IRAb-related disease is uncommon and possibly underdiagnosed or missed due to the lack of simple detection methods for IRAb. Our in-house user-friendly ELISA kit provides a valuable tool for diagnosis of this disease. |
| first_indexed | 2024-04-11T19:42:20Z |
| format | Article |
| id | doaj.art-ffc33648ef704d2ba17b74937c82a2b7 |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-04-11T19:42:20Z |
| publishDate | 2022-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-ffc33648ef704d2ba17b74937c82a2b72022-12-22T04:06:40ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922022-10-011310.3389/fendo.2022.10292971029297Development of a novel diagnostic assay for insulin receptor autoantibodies based on a patient with autoimmune hypoglycaemiaLeiluo Geng0Leiluo Geng1Cheuk-Lik Wong2Boya Liao3Ying Lin4Ying Lin5Hao Han6Hao Han7Karen S. L. Lam8Karen S. L. Lam9Aimin Xu10Aimin Xu11Aimin Xu12Chi-Ho Lee13Chi-Ho Lee14Vicki H. K. Tam15State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, Hong Kong SAR, ChinaDepartment of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong, Hong Kong SAR, ChinaDiabetes Centre, Department of Medicine and Geriatrics, Caritas Medical Centre, Hong Kong, Hong Kong SAR, ChinaSchool of Chinese Medicine, Hong Kong Baptist University, Hong Kong, Hong Kong SAR, ChinaState Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, Hong Kong SAR, ChinaDepartment of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong, Hong Kong SAR, ChinaState Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, Hong Kong SAR, ChinaDepartment of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong, Hong Kong SAR, ChinaState Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, Hong Kong SAR, ChinaDepartment of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong, Hong Kong SAR, ChinaState Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, Hong Kong SAR, ChinaDepartment of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong, Hong Kong SAR, ChinaDepartment of Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong, Hong Kong SAR, ChinaState Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, Hong Kong SAR, ChinaDepartment of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong, Hong Kong SAR, ChinaDiabetes Centre, Department of Medicine and Geriatrics, Caritas Medical Centre, Hong Kong, Hong Kong SAR, ChinaDifferential diagnosis of hypoglycaemia can at times be challenging for patients who appear to be well. Here we identify the case of a 66-year-old Chinese man presenting with recurrent episodes of fasting hypoglycaemia and confusion without any other manifestations. He had no personal or family history of diabetes, nor was he on any hypoglycaemic drugs. The fasting insulin levels were elevated while the C-peptide and pro-insulin levels were slightly low or normal. Antibodies against insulin were negative and levels of insulin-like growth factors were normal. A series of imaging diagnosis excluded the presence of insulinoma or ectopic insulin-secreting neuroendocrine tumor. Ultimately, insulin receptor autoantibodies (IRAb) were detected by both immunoprecipitation assay and enzyme-linked immunosorbent assay (ELISA) developed in house. In a cell study, the immunoglobulins isolated from this patient exerted insulin-like effects on stimulation of post-insulin receptor signaling and glucose uptake as well as inhibited 125I-insulin binding with insulin receptors. Collectively, this patient was diagnosed with IRAb-induced autoimmune hypoglycaemia. Although this patient had no obvious immune disorders, several autoantibodies were identified in his plasma samples, suggesting the patient might have mild aberrant autoimmunity and therefore generated IRAb. IRAb-related disease is uncommon and possibly underdiagnosed or missed due to the lack of simple detection methods for IRAb. Our in-house user-friendly ELISA kit provides a valuable tool for diagnosis of this disease.https://www.frontiersin.org/articles/10.3389/fendo.2022.1029297/fullautoimmune hypoglycaemiainsulin receptor autoantibodiestype B insulin resistancediagnosisELISA |
| spellingShingle | Leiluo Geng Leiluo Geng Cheuk-Lik Wong Boya Liao Ying Lin Ying Lin Hao Han Hao Han Karen S. L. Lam Karen S. L. Lam Aimin Xu Aimin Xu Aimin Xu Chi-Ho Lee Chi-Ho Lee Vicki H. K. Tam Development of a novel diagnostic assay for insulin receptor autoantibodies based on a patient with autoimmune hypoglycaemia Frontiers in Endocrinology autoimmune hypoglycaemia insulin receptor autoantibodies type B insulin resistance diagnosis ELISA |
| title | Development of a novel diagnostic assay for insulin receptor autoantibodies based on a patient with autoimmune hypoglycaemia |
| title_full | Development of a novel diagnostic assay for insulin receptor autoantibodies based on a patient with autoimmune hypoglycaemia |
| title_fullStr | Development of a novel diagnostic assay for insulin receptor autoantibodies based on a patient with autoimmune hypoglycaemia |
| title_full_unstemmed | Development of a novel diagnostic assay for insulin receptor autoantibodies based on a patient with autoimmune hypoglycaemia |
| title_short | Development of a novel diagnostic assay for insulin receptor autoantibodies based on a patient with autoimmune hypoglycaemia |
| title_sort | development of a novel diagnostic assay for insulin receptor autoantibodies based on a patient with autoimmune hypoglycaemia |
| topic | autoimmune hypoglycaemia insulin receptor autoantibodies type B insulin resistance diagnosis ELISA |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2022.1029297/full |
| work_keys_str_mv | AT leiluogeng developmentofanoveldiagnosticassayforinsulinreceptorautoantibodiesbasedonapatientwithautoimmunehypoglycaemia AT leiluogeng developmentofanoveldiagnosticassayforinsulinreceptorautoantibodiesbasedonapatientwithautoimmunehypoglycaemia AT cheuklikwong developmentofanoveldiagnosticassayforinsulinreceptorautoantibodiesbasedonapatientwithautoimmunehypoglycaemia AT boyaliao developmentofanoveldiagnosticassayforinsulinreceptorautoantibodiesbasedonapatientwithautoimmunehypoglycaemia AT yinglin developmentofanoveldiagnosticassayforinsulinreceptorautoantibodiesbasedonapatientwithautoimmunehypoglycaemia AT yinglin developmentofanoveldiagnosticassayforinsulinreceptorautoantibodiesbasedonapatientwithautoimmunehypoglycaemia AT haohan developmentofanoveldiagnosticassayforinsulinreceptorautoantibodiesbasedonapatientwithautoimmunehypoglycaemia AT haohan developmentofanoveldiagnosticassayforinsulinreceptorautoantibodiesbasedonapatientwithautoimmunehypoglycaemia AT karensllam developmentofanoveldiagnosticassayforinsulinreceptorautoantibodiesbasedonapatientwithautoimmunehypoglycaemia AT karensllam developmentofanoveldiagnosticassayforinsulinreceptorautoantibodiesbasedonapatientwithautoimmunehypoglycaemia AT aiminxu developmentofanoveldiagnosticassayforinsulinreceptorautoantibodiesbasedonapatientwithautoimmunehypoglycaemia AT aiminxu developmentofanoveldiagnosticassayforinsulinreceptorautoantibodiesbasedonapatientwithautoimmunehypoglycaemia AT aiminxu developmentofanoveldiagnosticassayforinsulinreceptorautoantibodiesbasedonapatientwithautoimmunehypoglycaemia AT chiholee developmentofanoveldiagnosticassayforinsulinreceptorautoantibodiesbasedonapatientwithautoimmunehypoglycaemia AT chiholee developmentofanoveldiagnosticassayforinsulinreceptorautoantibodiesbasedonapatientwithautoimmunehypoglycaemia AT vickihktam developmentofanoveldiagnosticassayforinsulinreceptorautoantibodiesbasedonapatientwithautoimmunehypoglycaemia |