Complement-independent pathogenic influences of anti-HMGCR + and anti-SRP + immune-mediated necrotizing myopathy autoantibodies on engineered muscle function
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
BACKGROUND: Immune-mediated necrotizing myopathy (IMNM) is a subgroup of idiopathic inflammatory myopathies associated with anti-signal recognition particle (SRP) or anti-3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) autoantibodies. The direct pathogenic effects of IMNM patient autoantibodies on skeletal muscle contractile force, independent of the downstream activation of the complement pathway, remain understudied. METHODS: (n = 7) autoantibodies and delivered in complement inactivated media for 4 days. hMMT function was then evaluated by quantifying the peak force and contraction kinetics in response to electrical field stimulation, followed by histological analysis of muscle cell gross morphology and sarcomere structure. To determine whether IgG from IMNM patients can enter muscle cells, 2-D myotube cultures were treated with donor total IgG delivered in complement replete media for 36 h, and then analyzed using immunostaining and confocal microscopy. RESULTS: Exposure to total IgGs isolated from a subset of IMNM patients induced a decline in hMMT twitch and tetanus contractile force and were associated with sarcomere fragility and slowed muscle cell contraction and relaxation rates. Pathogenic influences on hMMT force generation were observed at a greater frequency in response to total IgGs isolated from IMNM patients with anti-HMGCR + autoantibodies. Substantial intracellular human IgG staining was observed in conditions where myotubes were treated with total IgGs from IMNM patients. CONCLUSIONS: This study demonstrates that total IgGs isolated from IMNM patients have the aberrant capacity to enter muscle cells in the absence of complement. Further, a subset of patient IgGs exert direct pathogenic influences on engineered muscle contractile function that are independent of the complement system. Together, these findings have important implications for the advancement of IMNM precision medicine therapies.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.001 | 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 it