The Biology of Spondyloarthritis: Studies of the Host Immune Response in Experimental Chlamydia Infection and in Patients with Ankylosing Spondylitis.
Bibliographic record
Abstract
Spondyloarthritis (SpA) refers to a family of related inflammatory diseases affecting axial and peripheral joints. Reactive arthritis (ReA) and ankylosing spondylitis (AS) are both subsets of SpA. Despite the important role of HLA-B27 in conferring risk for SpA, a multitude of environmental and other genetic factors contribute to these diseases. This thesis contains two distinct halves that examine unique aspects of the SpA family of disease. The general aim of this thesis is to better understand host immunity in the context of the SpA family of diseases. The first half, comprised of Chapters 1-5, examines immune alterations in patients with AS. The second half, comprised of Chapters 6-9, examines how macrophages control host immunity to the ReA-associated bacteria, Chlamydia. Each half contains a comprehensive literature review in addition to peer-reviewed, primary scientific publications. The thesis is tied off by chapter 10, which provides future directions and conclusions. AS, the most common subset of SpA and the subset with the strongest HLA-B27 link, typically affects males in young adulthood. The TNF-inhibitors (TNFi) have proven to be effective at controlling the symptoms of AS but are not curative. Genetic and immunological studies have implicated the Th17 axis of inflammation in the pathogenesis of AS. The first half of this thesis discusses potential non-canonical roles of HLA-B27, documents an abnormal expansion of T cells associated with prolonged TNFi use, details a male sex bias in the Th17-axis, and examines the role of novel factors in driving the Th17-axis in AS patients. ReA is triggered by a prior infection with bacteria such as Chlamydia. How Chlamydia infection causes sequelae like ReA is unknown as the basic biology of host-pathogen interactions is not well understood. The second half of this thesis dissects the interaction of Chlamydia with the host immune system, focusing on the specific role of the macrophage in murine models of infection. In conclusion, a better understanding of environmental and genetic factors that contribute to the chronic inflammation of SpA will aid in understanding and treating these common, disabling diseases.
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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) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 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".