Association of Matrix Metalloproteinase-7 (MMP-7) With Clinical Outcomes in Different Stages of Systemic Sclerosis (SSc)
Bibliographic record
Abstract
Abstract RATIONALE: Systemic sclerosis (SSc) is an autoimmune disease characterized by endothelial dysfunction, immune system activation, and fibrosis, which can affect internal organs. SSc is clinically classified according to degree of skin fibrosis (limited vs diffuse). SSc-associated interstitial lung disease (SSc-ILD) affects 35-52% of patients, generally presenting with a non-specific interstitial pneumonia pattern (80%). Matrix metalloproteinase-7 (MMP-7) is increased in serum levels in patients with SSc and is associated with decreased lung function and increased risk of death or lung transplantation in patients with SSc-ILD. The goal of this project is to define the associations of MMP-7 with clinical outcomes in SSc in different disease stages. METHODS: Peripheral blood MMP-7 levels were obtained from biobanked plasma samples and were log-transformed for normalization. Cox proportional hazard models analyzed the association of MMP-7 with mortality. Linear models analyzed the association of MMP-7 with baseline percent predicted lung function (forced vital capacity, FVC; diffusion capacity for carbon monoxide, DLCO). Analyses were performed in all patients with SSc and in a subgroup of patients based on stage of SSc (early <3, intermediate 3-5, late 5-10, very late >10 years) at sample date. All models were adjusted for age at sample date, sex, race, smoking history, Area Deprivation Index, and diffuse versus limited scleroderma. Mortality models were additionally adjusted for baseline lung function (FVC, DLCO). RESULTS: Clinical data and biologic samples were prospectively collected from 341 patients with SSc enrolled between 2000-2023 in the Simmons Center for Interstitial Lung Disease Registry and Scleroderma Registry from 1980-2023 at the University of Pittsburgh. Analyses of MMP-7 with baseline lung function in SSc were consistent with prior work, demonstrating that each unit increase in log(MMP-7) was associated with a 16.01-unit decrease in baseline FVC percent and a 16.14-unit decrease in baseline DLCO percent. Table 1 demonstrates that MMP-7 has significant associations with worse lung function (FVC, DLCO) in patients with late and very late SSc disease stages. CONCLUSION: MMP-7 is significantly associated worse baseline lung function in patients with longer duration of disease, suggesting that the impact of MMP-7 in SSc is related to disease duration. Future directions involve further differentiating MMP-7 associations with SSc disease phenotypes, including limited versus diffuse, and evaluating for any modifying effects of associated antibodies. The relationship of disease duration with MMP-7 reveals new potential pathways for seeking targeted therapies at different disease stages in patients with SSc.
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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 | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 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 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".