Article ; Online: Autoantibodies against cytoskeletons and lysosomal trafficking discriminate sarcoidosis from healthy controls, tuberculosis and lung cancers.
Molecular biomedicine
2022 Volume 3, Issue 1, Page(s) 3
Abstract: Sarcoidosis is a systemic granulomatous disease of unknown etiology. Hypergammaglobulinemia and the presence of autoantibodies in sarcoidosis suggest active humoral immunity to unknown antigen(s). We developed a complex cDNA library derived from tissues ... ...
| Abstract | Sarcoidosis is a systemic granulomatous disease of unknown etiology. Hypergammaglobulinemia and the presence of autoantibodies in sarcoidosis suggest active humoral immunity to unknown antigen(s). We developed a complex cDNA library derived from tissues of sarcoidosis patients. Using a high throughput method, we constructed a microarray platform from this cDNA library containing large numbers of sarcoidosis clones. After selective biopanning, 1070 sarcoidosis-specifc clones were arrayed and immunoscreend with 152 sera from patients with sarcoidosis and other pulmonary diseases. To identify the sarcoidosis classifiers two statistical approaches were conducted: First, we identified significant biomarkers between sarcoidosis and healthy controls, and second identified markers comparing sarcoidosis to all other groups. At the threshold of an False Discovery Rate (FDR) < 0.01, we identified 14 clones in the first approach and 12 clones in the second approach discriminating sarcoidosis from other groups. We used the classifiers to build a naïve Bayes model on the training-set and validated it on an independent test-set. The first approach yielded an AUC of 0.947 using 14 significant clones with a sensitivity of 0.93 and specificity of 0.88, whereas the AUC of the second option was 0.92 with a sensitivity of 0.96 and specificity of 0.83. These results suggest robust classifier performance. Furthermore, we characterized the informative phage clones by sequencing and homology searches. Large numbers of classifier-clones were peptides involved in cellular trafficking and cytoskeletons. These results show that sarcoidosis is associated with a specific pattern of immunoreactivity that can discriminate it from other diseases. |
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| Language | English |
| Publishing date | 2022-01-20 |
| Publishing country | Singapore |
| Document type | Journal Article |
| ISSN | 2662-8651 |
| ISSN (online) | 2662-8651 |
| DOI | 10.1186/s43556-021-00064-x |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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