The Soluble Isoform of CTLA-4 Correlates with Interferon-α Activity in Systemic Lupus Erythematosus
Bibliographic record
Abstract
To the Editor: Systemic lupus erythematosus (SLE) is a multisystem autoimmune disorder characterized by fluctuating levels of immune response hyperactivity, high serum titers of nucleic antigen-specific autoantibodies, and persistent production of type-I interferon (IFN)1. One route to controlling SLE has been to exploit the properties of T cell lymphocyte costimulation inhibitor (CTLA-4), a selective costimulation inhibitor, which suppresses auto-antigen-specific T cell response intensity2. Although the full-length cell-surface receptor CTLA-4 is well characterized, other alternatively spliced isoforms exist, including a soluble form of the molecule (sCTLA-4)3. Initial analysis of sCTLA-4 in patients with SLE described raised serum levels compared with healthy donors, and sCTLA-4 levels correlated with disease activity4, but little is known of whether it plays any role in SLE. Currently, this is a relevant question because there is anecdotal evidence that CTLA4-Ig can have clinical benefits for some patients with SLE5. Studies of sCTLA-4 using current anti–CTLA-4 antibodies should be interpreted with caution because they are raised against the extracellular region, found in the receptor, cleaved receptor artifact and the soluble isoform, hence obscuring the contribution of native sCTLA-4. Here, using antibodies raised specifically against native sCTLA-46,7, we determined whether sCTLA-4 contributes to the immune response underlying SLE, particularly regarding SLE markers IFN-α and anti-dsDNA antibody levels. The study included 104 patients with SLE and 40 healthy volunteer donors and first compared serum levels of IFN-α (Figure 1). All methods were carried out in accordance with the Grampian … Address correspondence to F.J. Ward, University of Aberdeen, Immunity, Infection and Inflammation group, Division of Applied Medicine, Institute of Medical Sciences, Foresterhill, Aberdeen, UK. E-mail: mmd475{at}abdn.ac.uk or L.N. Dahal, L.N.Dahal{at}liverpool.ac.uk
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.
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 | 0.002 | 0.005 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.003 | 0.004 |
| Insufficient payload (model declined to judge) | 0.003 | 0.002 |
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".