1. |
- Bastard, Paul, et al.
(author)
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Preexisting autoantibodies to type I IFNs underlie critical COVID-19 pneumonia in patients with APS-1.
- 2021
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In: The Journal of experimental medicine. - 1540-9538. ; 218:7
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Journal article (peer-reviewed)abstract
- Patients with biallelic loss-of-function variants of AIRE suffer from autoimmune polyendocrine syndrome type-1 (APS-1) and produce a broad range of autoantibodies (auto-Abs), including circulating auto-Abs neutralizing most type I interferons (IFNs). These auto-Abs were recently reported to account for at least 10% of cases of life-threatening COVID-19 pneumonia in the general population. We report 22 APS-1 patients from 21 kindreds in seven countries, aged between 8 and 48 yr and infected with SARS-CoV-2 since February 2020. The 21 patients tested had auto-Abs neutralizing IFN-α subtypes and/or IFN-ω; one had anti-IFN-β and another anti-IFN-ε, but none had anti-IFN-κ. Strikingly, 19 patients (86%) were hospitalized for COVID-19 pneumonia, including 15 (68%) admitted to an intensive care unit, 11 (50%) who required mechanical ventilation, and four (18%) who died. Ambulatory disease in three patients (14%) was possibly accounted for by prior or early specific interventions. Preexisting auto-Abs neutralizing type I IFNs in APS-1 patients confer a very high risk of life-threatening COVID-19 pneumonia at any age.
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2. |
- Burbelo, Peter D., et al.
(author)
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A new luminescence assay for autoantibodies to mammalian cell-prepared insulinoma-associated protein 2
- 2008
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In: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 31:9, s. 1824-1826
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Journal article (peer-reviewed)abstract
- OBJECTIVE - Insulinoma-associated protein 2 (IA-2) is a major autoantigen in type I diabetes, and IA-2 autoantibodies are routinely detected by a liquid-phase radioimmunoprecipitation assay. The present experiments were initiated to develop a new assay that does not require the use of radioisotopes or autoantigens prepared in bacteria or by in vitro transcription/translation. RESEARCH DESIGN AND METHODS - IA-2 luciferase fusion protein was expressed in mammalian cells and assayed for autoantibodies by liquid-phase luciferase immunoprecipitation. RESULTS - Our study showed that there was no significant difference between the luciferase immunoprecipitation and the radioimmunoprecipitation assays in sensitivity and specificity, and comparison of the two assays revealed a high correlation coefficient (R-2 = 0.805). CONCLUSIONS - The luciferase system offers a robust, inexpensive, nonradioactive method for the detection of autoantibodies to mammalian cell-prepared IA-2 and could be of practical value at the clinical level.
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3. |
- Burbelo, Peter D., et al.
(author)
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Comparison of Radioimmunoprecipitation With Luciferase Immunoprecipitation for Autoantibodies to GAD65 and IA-2 beta
- 2010
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In: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 33:4, s. 754-756
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Journal article (peer-reviewed)abstract
- OBJECTIVE - To compare the sensitivity and specificity of luciferase immunoprecipitation (LIPS) with radioimmunoprecipitation (RIP) for the measurement of autoantibodies to the type 1 diabetes autoantigens glutamic acid decarboxylase 65 (GAD65) and insulinoma-associated protein (IA)-2 beta. RESEARCH DESIGN AND METHODS - Sera from 49 type 1 diabetic patients and 100 nondiabetic control subjects from Diabetes Antibody Standardization Program 2007 were used to screen for autoantibodies to GAD65. An additional 200 type 1 diabetic patients and 200 nondiabetic control subjects were used to validate the GAD65 results and screen for autoantibodies to IA-2 beta. RESULTS - LIPS showed equal sensitivity and specificity to RIP for detecting autoantibodies to GAD65 and IA-2 beta. Receiver-operating characteristic analysis revealed that the detection of autoantibodies to GAD65 and IA-2 beta by LIPS and RIP were not statistically different. CONCLUSIONS - The LIPS assay does not require the use of radioisotopes or in vitro transcription/translation and is a practical alternative at the clinical level for the RIP assay.
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