Membrane-bound complement regulator expression in peripheral nerves
Bibliographic record
Abstract
Abstract BACKGROUND: Homozygous CD59-deficient patients manifest with recurrent peripheral neuropathy resembling Guillain-Barré syndrome (GBS), hemolytic anemia and recurrent strokes. Variable mutations in CD59, leading to loss of function, have been described, and overall, 17/18 of patients with any mutation presented with recurrent GBS. Here we determine the expression and possible role of membrane-bound complement regulators including CD59, in the peripheral nervous system (PNS) of mice and humans. MAIN: Methods. We examined the expression of membrane-bound complement regulators in the peripheral nerves of healthy humans and a CD59-deficient patient, as well as in wild-type (WT) and CD59a-deficient mice. Cross sections of teased sciatic nerves and myelinating dorsal root ganglia (DRG) neuron/Schwann cell cultures were examined by confocal and electron microscopy. Results. We demonstrate that CD59-deficient mice display normal peripheral nerve morphology but develop myelin abnormalities in older age. They normally express P0, ankyrin G (AnkG), caspr, dystroglycan, and neurofascin. CD59 is colocalized with myelin basic protein (MBP) and P0 and is present in compact myelin and endothelium but absent from noncompact myelin. Furthermore, immunolabeling of WT nerves using antibodies to CD59 and AnkG revealed that CD59 was localized along the internode but was absent from the nodes of Ranvier. Finally, we show that the nodes of Ranvier lack other complement-membrane regulatory proteins, including CD46, CD55, CD35, and Crry, rendering this area highly exposed to complement attack. CONCLUSION: Myelin in the human PNS is protected only by CD59 and CD55, and not by CD46 or CD35, rendering myelin in the PNS vulnerable to complement attack and demyelination in autoinflammatory Guillain-Barre syndrome, as seen in CD59 deficiency.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.002 |
| Research integrity | 0.000 | 0.002 |
| Insufficient payload (model declined to judge) | 0.001 | 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".