The Role of Natural Killer Cells in Inflammation in Active Adult-onset Still Disease
Bibliographic record
Abstract
Adult-onset Still disease (AOSD) is a systemic inflammatory disease characterized by spiking fever, arthralgia, rash, leukocytosis, and hepatosplenomegaly, similar to systemic-onset juvenile idiopathic arthritis (sJIA)1,2. The etiology of AOSD is unclear but the disease is thought to result from a combination of genetic and environmental factors. The disease pathology is characterized by widespread immune dysregulation, involving cytokines and their receptors, immune cells, and tissues. Activation of the innate immune system plays a major role in the systemic inflammation that characterizes AOSD and sJIA3. Activated macrophages and neutrophils induce increased levels of proinflammatory cytokines, such as interleukin (IL)-1β, IL-18, IL-6, and interferon (IFN)-γ. These proinflammatory cytokines provoke activation of macrophages and neutrophils, and differentiation of T cells. Decreased numbers and functional impairment of natural killer (NK) cells have also been implicated in the pathogenesis of AOSD and sJIA4,5. NK cells are an important lymphocytic component of the innate immune system, providing a cytotoxicity defense against malignant, infected, and autoreactive cells6,7. NK cells exert their effects by secreting cytolytic granules such as perforin, granzyme, and serine proteases, and induce caspase-dependent apoptosis through death receptors including Fas/FasL. Impaired cytotoxic function of NK cells leads to excessive activation of macrophages and T cells, as seen in macrophage activation syndrome (MAS), and is a major, life-threatening complication of AOSD and sJIA8,9. Primary hemophagocytic lymphohistiocytosis (HLH), a hereditary disorder of MAS, occurs as a result of genetic defects in the perforin- or granzyme-dependent pathways of NK cells or cytotoxic T cells10. Additional genetic mutations associated with inhibitory or stimulatory NK cell receptors have also been observed in secondary HLH. The resulting failure of NK cells to lyse activated antigen-presenting cells results in sustained stimulation of lymphocytes … Address correspondence to Dr. H.A. Kim, Department of Rheumatology, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon 16499, Korea. E-mail: nakhada{at}naver.com
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 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 | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| 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".