Causal Association Between Peripheral Blood Immune Cells and Spondyloarthritis Phenotypes
Bibliographic record
Abstract
Objectives Complex genetic signatures in immune cells underlie SpA phenotypes, including axial SpA and psoriatic disease. Recently, GWAS data for these 731 immune traits can be found in the IEU Open GWAS project from a cohort of 3,757 Sardinians noted 122 significant independent association signals, over 40% overlapped with autoimmune disease.[1] However, a possible causal relationship between immune cells and disease cannot be determined. To evaluate the causal association between immunological characteristics and ankylosing spondylitis (AS), psoriatic arthritis (PsA), and psoriasis (PsV), a bidirectional, two-sample Mendelian randomization (MR) approach was performed in this study. Methods 1462 pts with AS, 1553 pts with PsA, and 4510 patients with psoriasis were analyzed. The control population ranged from 147,221 to 212,242 samples, and over 16 million SNPs were used in the analysis. Instrument selection for MR included single-nucleotide variations (SNVs) with a genome-wide significance threshold of 5 × 10^-8 for AS, PsA, and PsV and a Genome-wide significance threshold of 5 × 10^-6 for immune traits. MR was assessed using the Inverse variance weighted (IVW) method. Results For immune cells leading to AS, the top 2 associations were HLA-DR on CD14-CD16+ monocytes [OR 0.66 (0.54-0.8200), p=0.00010] and HLA-DR+CD4+ T cell absolute count [OR 1.77 (1.25-2.49), p=0.00117]. For immune cells leading to PsA, the top 2 associations were CD8 on terminally differentiated CD8+ T cell [OR 1.33 (1.15-1.53, p=.00009] and Hematopoietic Stem Cell Absolute Count [OR 1.13 (1.04, 1.24), p=0.00432]. Finally, for immune cells leading to psoriasis, the top 2 associations were CD28-CD4-CD8- T cell absolute count [OR 0.89 (0.83-0.95), p=0.00069] and CD8 on terminally differentiated CD8+ T cell [OR 1.19 (1.07-1.32), p=0.00099]. The p-values reported are not corrected for multiple testing. Conclusion Multiple immune cells leading to SpA phenotypes have been identified. Some of these cell types, such as HLA-DR on CD14-CD16+ monocytes and double negative T cells (CD4-CD8-), have already been implicated in the pathogenesis of SpA. Further interrogation of the data may help link specific immune cell subtypes to immune-mediated disorders, identify candidate causal candidate genes, establish the direction of effect, and offer new insight into the pathogenesis of the disease. [1.] Orrù V. Nat Genet 2020;52:1036-1045.
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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 | 0.003 | 0.009 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.006 | 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".