Proteomics Used To Identify the Target of a Platelet Aggregating Antibody in a Patient with HUS.
Bibliographic record
Abstract
Abstract Hemolytic Uremic Syndrome (HUS) has considerable overlap with Thrombotic Thrombocytopenia Purpura (TTP). Recently, evidence is emerging to suggest that TTP, like HIT, is an immune mediated disorder. We have investigated the plasmas of patients with Hemolytic Uremic Syndrome to determine the presence of antibodies and the specificity of the related antigens. Methods: A 20 year old female presented with repeated episodes of HUS. She is dialysis dependent. Plasma was taken for VWF, multimers, platelet aggregation, metalloprotease and inhibitor, western blot and 2D PAGE analysis. Results: At the time of the acute episodes, the VWF was increased three fold; the VWF multimer patterns on two occasions showed the presence of unusually large VWF forms. The metalloprotease was normal at all times and no inhibitor was present. Her platelets showed a normal response to aggregation, however, the plasma caused spontaneous aggregation of normal washed human platelets. This reactivity was removed after absorption with Staph A. On western blot analysis of platelet and microvascular endothelial cell lysate vs. patient plasma, multiple reactions were detected with a strong and persistent reactivity against antigens of 200,00 kDa and 55 kDa. Two dimensional PAGE of the whole platelet proteome identified strong immunoreactivity with two target spots in the 55 kDa area. Mass spectroscopy, using the nano-LC-MS/MS analysis, with the MASCOT search program confirmed the target antigen as beta fibrin with a molecular weight of 50.731 and an isoelectric point of 7.95 with a MASCOT score of 859 and 750 respectively. Conclusions: Anti-platelet antibodies which cross-react with platelet and microvascular endothelial cells are present in the plasma of patients with recurrent episodes of HUS. These antibodies cause aggregation of normal human platelets and are removed following specific absorption of IgG from the plasma. 2D proteomic analysis indicates that the antibody in our patient was directed against a specific antigen, B fibrin. The data suggests that HUS, like TTP and HIT has an immunological basis.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".