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Peer-reviewedCC BY 4.0Biomolecules

The Proteomic Profiling of a Platelet-Enriched Fraction Identifies an Inflammatory and Immune-Related Signature Associated with Non-Response to Treatment with Plasma Rich in Growth Factors in Knee Osteoarthritis

  • Alessandra Colombini1
  • Vincenzo Raffo2
  • Elena De Vecchi3
  • Laura Pandolfi3
  • Emiliano Marasco4
  • Giulio Grieco1
  • Simona Landoni1
  • Margot Lo Pinto5
  • Simone Dario Scilabra5
  • Laura de Girolamo1
5 affiliations
  1. 1Orthopaedic Biotechnology Lab, IRCCS Galeazzi-Sant’Ambrogio Hospital, 20157 Milan, Italy
  2. 2Department of Precision and Regenerative Medicine and Ionian Area (Di. Me. Pre-J), University of Bari, 70124 Bari, Italy
  3. 3Laboratory of Clinical Chemistry and Microbiology, IRCCS Galeazzi-Sant’Ambrogio Hospital, 20157 Milan, Italy
  4. 4Division of Rheumatology, Bambino Gesù Children’s Hospital, 00165 Rome, Italy
  5. 5Proteomics Group of Ri. MED Foundation, Research Department IRCCS ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione), 90133 Palermo, Italy
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Abstract

Background: The use of plasma rich in growth factors (PRGF) is a promising regenerative treatment for knee osteoarthritis (OA), but clinical response is heterogeneous. This study aimed to identify molecular features and explore clinical factors associated with PRGF non-response and explore potential biomarkers for patient stratification. Methods: One hundred patients with knee OA (Kellgren–Lawrence II–III) treated with two intra-articular PRGF injections were evaluated at baseline and 6 months. Clinical response was defined by a ≥8-point improvement in overall knee injury and osteoarthritis outcome score (KOOS). Exploratory proteomic profiling was performed in a subgroup of 33 patients (13 responders and 20 non-responders) using platelet-rich plasma-derived platelet lysate (PRP-PL) generated from the same blood-derived preparation used for treatment. Samples were analyzed by data-independent acquisition mass spectrometry, followed by a bioinformatic analysis of differential proteins and enriched pathways. To further investigate selected proteomic findings, IgA levels were quantified in PRP-PL from the entire cohort. Results: Responders showed significant improvements in pain, overall KOOS, and functional outcomes. Proteomic analysis identified a non-responder signature characterized by increased immunoglobulin chains, complement-related proteins, acute-phase molecules, extracellular matrix remodeling proteins, and metabolic stress markers. Functional enrichment revealed the activation of immune, inflammatory, and tissue remodeling pathways. IgA levels in PRP-PL were significantly higher in non-responders, consistent with the immunoglobulin-related proteomic findings. Conclusions: PRGF non-response is associated with an inflammatory and immune-related phenotype. Higher IgA levels in PRP-PL were associated with reduced treatment responsiveness and may help identify a biological phenotype less likely to benefit from PRGF treatment.

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Cite

BibTeXRIS
BibTeX
@article{colombini2026proteomic,
  title = {{The Proteomic Profiling of a Platelet-Enriched Fraction Identifies an Inflammatory and Immune-Related Signature Associated with Non-Response to Treatment with Plasma Rich in Growth Factors in Knee Osteoarthritis}},
  author = {Alessandra Colombini and Vincenzo Raffo and Elena De Vecchi and Laura Pandolfi and Emiliano Marasco and Giulio Grieco and Simona Landoni and Margot Lo Pinto and Simone Dario Scilabra and Laura de Girolamo},
  journal = {Biomolecules},
  year = {2026},
  month = oct,
  doi = {10.3390/biom16101482},
  url = {https://www.mdpi.com/2218-273X/16/10/1482},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - The Proteomic Profiling of a Platelet-Enriched Fraction Identifies an Inflammatory and Immune-Related Signature Associated with Non-Response to Treatment with Plasma Rich in Growth Factors in Knee Osteoarthritis
AU  - Alessandra Colombini
AU  - Vincenzo Raffo
AU  - Elena De Vecchi
AU  - Laura Pandolfi
AU  - Emiliano Marasco
AU  - Giulio Grieco
AU  - Simona Landoni
AU  - Margot Lo Pinto
AU  - Simone Dario Scilabra
AU  - Laura de Girolamo
PY  - 2026
DA  - 2026/10/01
JO  - Biomolecules
DO  - 10.3390/biom16101482
UR  - https://www.mdpi.com/2218-273X/16/10/1482
AB  - Background: The use of plasma rich in growth factors (PRGF) is a promising regenerative treatment for knee osteoarthritis (OA), but clinical response is heterogeneous. This study aimed to identify molecular features and explore clinical factors associated with PRGF non-response and explore potential biomarkers for patient stratification. Methods: One hundred patients with knee OA (Kellgren–Lawrence II–III) treated with two intra-articular PRGF injections were evaluated at baseline and 6 months. Clinical response was defined by a ≥8-point improvement in overall knee injury and osteoarthritis outcome score (KOOS). Exploratory proteomic profiling was performed in a subgroup of 33 patients (13 responders and 20 non-responders) using platelet-rich plasma-derived platelet lysate (PRP-PL) generated from the same blood-derived preparation used for treatment. Samples were analyzed by data-independent acquisition mass spectrometry, followed by a bioinformatic analysis of differential proteins and enriched pathways. To further investigate selected proteomic findings, IgA levels were quantified in PRP-PL from the entire cohort. Results: Responders showed significant improvements in pain, overall KOOS, and functional outcomes. Proteomic analysis identified a non-responder signature characterized by increased immunoglobulin chains, complement-related proteins, acute-phase molecules, extracellular matrix remodeling proteins, and metabolic stress markers. Functional enrichment revealed the activation of immune, inflammatory, and tissue remodeling pathways. IgA levels in PRP-PL were significantly higher in non-responders, consistent with the immunoglobulin-related proteomic findings. Conclusions: PRGF non-response is associated with an inflammatory and immune-related phenotype. Higher IgA levels in PRP-PL were associated with reduced treatment responsiveness and may help identify a biological phenotype less likely to benefit from PRGF treatment.
SN  - 2218-273X
ER  -