Contribution of VH Replacement Products to the Generation of Autoreactive Antibodies in Systemic Lupus Erythematosus (129.4)
Bibliographic record
Abstract
Abstract Systemic lupus erythematosus (SLE) is characterized by the production of high affinity autoantibodies against various nuclear antigens. To gain insight into the mechanisms of autoantibody generation during the course of SLE, we performed single cell PCR analysis and obtained about 200 IgH genes with paired Igκ or Igλ genes from the plasma cells (CD19lowCD27high) and naïve B cells (CD19+CD27−) of three SLE patients. The SLE derived IgH genes have longer CDR3 regions with enriched Arg residues, which are the common features of autoantibodies. SLE plasma cells derived IgH and IgL genes are highly mutated, indicating their positive selection and active involvement in the abnormal immune responses. Interestingly, analyses of the IgL and IgH genes derived from SLE patients showed signs of excessive secondary recombination when compared with those from healthy donors, such as elevated usages of downstream Jκ4, Jκ5, and Jλ3 genes in the IgL genes and concurrently, significantly elevated frequencies of VH replacement products in the IgH genes derived from SLE patients. All the VH replacement “footprints” preferentially contribute charged amino acids into the IgH CDR3 regions. Initial testing of 12 recombinant antibodies derived from SLE plasma cells showed seven of them recognize peri-nuclear antigens. Importantly, the identified VH replacement products directly encode autoantibodies. These findings revealed for the first time that excessive secondary recombination occurred on both IgL and IgH genes in SLE patients and the enriched VH replacement products in SLE plasma cells directly encode autoantibodies.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| 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) | 0.001 | 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 source (direct Gemma or distilled Codex), 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".