Dataset Information

Two circulating biomarkers are associated with the serological status of Rheumatoid Arthritis patients: a tool for precision medicine strategies

ABSTRACT: In the present work, we aimed to carry out a pipeline based on quantitative proteomics tools to discover, verify and validate circulating proteins that are associated with the presence in serum of RF and ACPA and may therefore have potential for the stratification of RA patients and the application of precision medicine strategies based on these molecular signatures.

INSTRUMENT(S): 4800 Proteomics Analyzer

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Plasma

SUBMITTER: Valentina Calamia

LAB HEAD: Valentina Calamia

PROVIDER: PXD037386 | Pride | 2023-03-11

REPOSITORIES: Pride

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Association of the serological status of rheumatoid arthritis patients with two circulating protein biomarkers: A useful tool for precision medicine strategies.

Ruiz-Romero Cristina C Fernández-Puente Patricia P González Lucía L Illiano Anna A Lourido Lucía L Paz Rocío R Quaranta Patricia P Perez-Pampín Eva E González Antonio A Blanco Francisco J FJ Calamia Valentina V

Frontiers in medicine 20221028

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation of the joints and presence of systemic autoantibodies, with a great clinical and molecular heterogeneity. Rheumatoid Factor (RF) and anti-citrullinated protein antibodies (ACPA) are routinely used for the diagnosis of RA. However, additional serological markers are needed to improve the clinical management of this disease, allowing for better patient stratification and the desirable application of precision ...[more]

PMID: 36388911

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Project description:Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation of the joints and presence of systemic autoantibodies, with a great clinical and molecular heterogeneity. Rheumatoid Factor (RF) and anti-citrullinated protein antibodies (ACPA) are routinely used for the diagnosis of RA. However, additional serological markers are needed to improve the clinical management of this disease, allowing for better patient stratification and the desirable application of precision medicine strategies. In the present study, we investigated those systemic molecular changes that are associated with the RF and ACPA status of RA patients. To achieve this objective, we followed a proteomic biomarker pipeline from the discovery phase to validation. First, we performed an iTRAQ-based quantitative proteomic experiment on serum samples from the RA cohort of the Hospital of Santiago de Compostela (CHUS). In this discovery phase, serum samples from the CHUS cohort were pooled according to their RF/ACPA status. Shotgun analysis revealed that, in comparison with the double negative group (RF-/ACPA-), the abundance of 12 proteins was altered in the RF+/ACPA+ pool, 16 in the RF+/ACPA- pool and 10 in the RF-/ACPA+ pool. Vitamin D binding protein and haptoglobin were the unique proteins increased in all the comparisons. For the verification phase, 80 samples from the same cohort were analyzed individually. To this end, we developed a Multiple Reaction Monitoring (MRM) method that was employed in a comprehensive targeted analysis with the aim of verifying the results obtained in the discovery phase. Thirty-one peptides belonging to 12 proteins associated with RF and/or ACPA status were quantified by MRM. In a final validation phase, the serum levels of alpha-1-acid glycoprotein 1 (A1AG1), haptoglobin (HPT) and retinol-binding protein 4 (RET4) were measured by immunoassays in the RA cohort of the Hospital of A Coruña (HUAC). The increase of two of these putative biomarkers in the double seropositive group was validated in 260 patients from this cohort (p = 0.009 A1AG1; p = 0.003 HPT). The increased level of A1AG1 showed association with RF rather than ACPA (p = 0.023), whereas HPT showed association with ACPA rather than RF (p = 0.013). Altogether, this study has allowed a further classification of the RA seropositive patients into two novel clusters: RF+A1AG+ and ACPA+HPT+. The determination of A1AG1 and HPT in serum would provide novel information useful for RA patient stratification, which could facilitate the effective implementation of personalized medicine in routine clinical practice.

			Action	DRS
	FDR_SN80.group	Other
	FDR_SN80_MGFPeaklist.mgf	Mgf
	iTRAQ_13_31_10.mzml	Mzml
	iTRAQ_13_31_2.mzml	Mzml
	iTRAQ_13_31_7.mzml	Mzml