A Peripheral Blood Signature of Increased Th1 and Myeloid Cells Combined with Serum Inflammatory Mediators Is Associated with Response to Abatacept in Rheumatoid Arthritis Patients
Panagiota Goutakoli,
Garyfalia Papadaki,
Argyro Repa,
Nestor Avgoustidis,
Eleni Kalogiannaki,
Irini Flouri,
Antonios Bertsias,
Jerome Zoidakis,
Martina Samiotaki,
George Bertsias,
Maria Semitekolou,
Panayotis Verginis,
Prodromos Sidiropoulos
Affiliations
Panagiota Goutakoli
Laboratory of Rheumatology, Autoimmunity and Inflammation, Medical School, University of Crete, 71003 Heraklion, Greece
Garyfalia Papadaki
Laboratory of Rheumatology, Autoimmunity and Inflammation, Medical School, University of Crete, 71003 Heraklion, Greece
Argyro Repa
Rheumatology and Clinical Immunology, University Hospital of Heraklion, 71003 Heraklion, Greece
Nestor Avgoustidis
Rheumatology and Clinical Immunology, University Hospital of Heraklion, 71003 Heraklion, Greece
Eleni Kalogiannaki
Rheumatology and Clinical Immunology, University Hospital of Heraklion, 71003 Heraklion, Greece
Irini Flouri
Rheumatology and Clinical Immunology, University Hospital of Heraklion, 71003 Heraklion, Greece
Antonios Bertsias
Rheumatology and Clinical Immunology, University Hospital of Heraklion, 71003 Heraklion, Greece
Jerome Zoidakis
Department of Biotechnology, Biomedical Research Foundation, Academy of Athens, 11527 Athens, Greece
Martina Samiotaki
Protein Chemistry Facility, Biomedical Sciences Research Center “Alexander Fleming”, 16672 Athens, Greece
George Bertsias
Laboratory of Rheumatology, Autoimmunity and Inflammation, Medical School, University of Crete, 71003 Heraklion, Greece
Maria Semitekolou
Laboratory of Rheumatology, Autoimmunity and Inflammation, Medical School, University of Crete, 71003 Heraklion, Greece
Panayotis Verginis
Laboratory of Immune Regulation and Tolerance, Division of Basic Sciences, Medical School, University of Crete, 71003 Heraklion, Greece
Prodromos Sidiropoulos
Laboratory of Rheumatology, Autoimmunity and Inflammation, Medical School, University of Crete, 71003 Heraklion, Greece
Abatacept (CTLA4-Ig)—a monoclonal antibody which restricts T cell activation—is an effective treatment for rheumatoid arthritis (RA). Nevertheless, only 50% of RA patients attain clinical responses, while predictors of response are rather limited. Herein, we aimed to investigate for early biomarkers of response to abatacept, based on a detailed immunological profiling of peripheral blood (PB) cells and serum proteins. We applied flow cytometry and proteomics analysis on PB immune cells and serum respectively, of RA patients starting abatacept as the first biologic agent. After 6 months of treatment, 34.5% of patients attained response. At baseline, Th1 and FoxP3+ T cell populations were positively correlated with tender joint counts (p-value = 0.047 and p-value = 0.022, respectively). Upon treatment, CTLA4-Ig effectively reduced the percentages of Th1 and Th17 only in responders (p-value = 0.0277 and p-value = 0.0042, respectively). Notably, baseline levels of Th1 and myeloid cell populations were significantly increased in PB of responders compared to non-responders (p-value = 0.009 and p-value = 0.03, respectively). Proteomics analysis revealed that several inflammatory mediators were present in serum of responders before therapy initiation and strikingly 10 amongst 303 serum proteins were associated with clinical responses. Finally, a composite index based on selected baseline cellular and proteomics’ analysis could predict response to abatacept with a high sensitivity (90%) and specificity (88.24%).
