Translational Research //
1. Metabolomics Profile Predicts Carotid Atherosclerosis Progression in Psoriatic Disease
Metabolomic profiling of patients with psoriatic disease (PsD) offers unparalleled opportunity to unravel the molecular and clinical interactions linking PsD with cardiovascular (CV) risk. Our objective was to evaluate the metabolomics profile in patients with PsD vs. non-psoriatic controls and to assess its association with carotid atherosclerosis progression.
2. Role of miRNA-21-5p As a Potential Biomarker for the Inflammation Pathway in Psoriatic Disease and Response to Methotrexate Treatment
miRNAs are small non coding RNAs whose main function, at a post transcriptional level, is to modulate the expression of target genes via translation inhibition or mRNA degradation. Several studies have shown links between altered miRNA expression with the pathogenesis of several autoimmune disorders. We demonstrated earlier that miR-21-5p was upregulated in PsA and psoriasis without arthritis (PsC) compared to healthy controls (HC) (p<0.001), thus a potential biomarker for PsA. We aimed to determine whether miR-21-5p modulates inflammation in psoriatic disease (PsD = PsA & PsC) through IL-17/IL-23 axis, and determine its role in the treatment response to methotrexate (MTX).
3. −21 HLA-Class I Dimorphism Differentiates Psoriatic Arthritis (PsA) from Psoriasis without Psoriatic Arthritis (PsC)
The association between human leukocyte antigen (HLA) class I alleles and psoriatic disease indicates a potential role for the innate immune system in disease pathogenesis. HLA class I educates NK cells through interactions with killer cell Immunoglobulin receptors (KIRs) and by supplying peptides that bind HLA-E to form ligands for the more conserved CD94/NKG2A NK receptors. The peptides corresponding to residues −22 to −14 of the leader sequence of HLA-A, HLA-B, and HLA-C specifically bind to the binding site of HLA-E. In ~80% of HLA-B allotypes, methionine at position −21M (21M) is replaced by threonine. Methionine −21 delivers functional peptides, whereas threonine at this position (−21T) does not. This functional dimorphism divides the human population into three groups: −21M/M, M/T, and T/T, with decreased order of potency of the NK CD94/NKG2A+ receptor. We aimed to determine whether the distribution of the M and T haplotypes differed between patients with PsA, PsC and healthy controls.
4. Resolving the Synovial Fluid Proteome and Peptidome for Disease-Specific Mediators of Inflammatory Arthritis
Idiopathic inflammatory arthritis (IA) is a T-cell driven chronic condition characterized an imbalance in cell proliferation and apoptosis leading to significant synovial hyperplasia and degradation of the underlying cartilage and bone. The exact etiology of IA is still poorly understood with studies aimed at delineating the molecular pathways driving loss of immunological tolerance to the body’s self-antigens. Naturally, there is a compelling need to identify markers of aberrant immune pathways which may advance current insights into the molecular mechanisms of IA and serve as clinical markers for disease monitoring and treatment responses. Using mass spectrometry (MS), we aim to provide a detailed analysis of the proteome and peptidome of IA synovial fluid (SF).