More than Skin Deep: The Cutaneous Microbiome of Psoriasis and Psoriatic Arthritis
Bibliographic record
Abstract
Psoriasis is a common inflammatory skin disease affecting 3% of the Canadian population. Psoriatic arthritis (PsA) is an inflammatory arthritis that affects about 24% of psoriasis patients. Together, psoriasis and PsA are referred to as psoriatic disease (PsD), a complex genetic disease with clinical and genetic heterogeneity. Disease manifestations are varied and are partly explained by genetic heterogeneity: human leukocyte antigen (HLA)-C*06 is the strongest genetic risk factor for psoriasis without arthritis (PsC), while HLA-B*27 and other HLA-B alleles, which carry glutamate amino acid residue at position 45 (HLA-Bglu45), are associated with PsA. Genes implicated in skin barrier function are also associated with psoriasis, especially PsC, and interact with HLA-C*06. Yet, despite much progress in the study of genetics in PsD, its pathogenesis is not fully understood, inspiring an interest in the role of environmental factors. One such factor is streptococcal infection, which has long been linked to the onset and exacerbation of psoriasis vulgaris, particularly in HLA-C*06-positive patients. Additionally, there is evidence to suggest a role for a bacterial antigen in the development of PsA. In this work, I aimed to investigate the skin microbiome in psoriatic disease and determine whether the psoriatic microbiome is associated with the psoriatic phenotype or genotype. I first defined the current state of evidence on the skin microbiome in PsD by conducting a systematic literature review, revealing that despite difference in methodology between studies, the psoriatic microbiome is characterized by decreased alpha diversity, higher relative abundances of Firmicutes, and lower relative abundances of Actinobacteria compared to healthy controls. I subsequently examined the variables involved in skin microbiome research to optimize collection and DNA isolation methodologies and demonstrated that Zymo or MoBio kits with the Puritan swab and either of the collection fluids (Specimen Collection Fluid [SCF] or phosphate buffered saline [PBS]) are suitable for skin microbiome studies. Lastly, I compared the skin microbiome between the different clinical phenotypes and genotypes of PsD and demonstrated that HLA-C*06-positive lesions are characterized by an increased alpha diversity compared with HLA-Bglu45-positive lesions, while clinical phenotypes and the genes implicated in skin barrier function are not associated with differences in alpha or beta diversity. Altogether, this work has defined the gaps in knowledge of the skin microbiome in PsD, standardized collection and DNA isolation protocols for skin microbiome studies and advanced our knowledge of the skin microbiome in PsD, thereby paving way for further research into the pathogenesis of this disease.
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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 | 0.002 | 0.012 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.003 | 0.003 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 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".