AUTHOR=Makris Anastasia , Adamidi Sofia , Koutsianas Christos , Tsalapaki Christina , Hadziyannis Emilia , Vassilopoulos Dimitrios 

TITLE=Increased Frequency of Peripheral B and T Cells Expressing Granulocyte Monocyte Colony-Stimulating Factor in Rheumatoid Arthritis Patients

JOURNAL=Frontiers in Immunology

VOLUME=8

YEAR=2018

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2017.01967

DOI=10.3389/fimmu.2017.01967

ISSN=1664-3224

ABSTRACT=<sec id="ST1"><title>Objectives</title><p>Granulocyte monocyte colony-stimulating factor (GM-CSF) is currently considered a crucial inflammatory mediator and a novel therapeutic target in rheumatoid arthritis (RA), despite the fact that its precise cellular sources remain uncertain. We studied the expression of GM-CSF in peripheral lymphocytes from RA patients and its change with antirheumatic therapies.</p></sec><sec id="ST2"><title>Methods</title><p>Intracellular GM-CSF expression was assessed by flow cytometry in stimulated peripheral B (CD19+) and T (CD3+) cells from RA patients (<italic>n</italic> = 40), disease (<italic>n</italic> = 31 including osteoarthritis <italic>n</italic> = 15, psoriatic arthritis <italic>n</italic> = 10, and systemic rheumatic diseases <italic>n</italic> = 6) and healthy (<italic>n</italic> = 16) controls. The phenotype of GM-CSF+ B cells was assessed as well as longitudinal changes in GM-CSF+ lymphocytes during methotrexate (MTX, <italic>n</italic> = 10) or anti-tumor necrosis factor (anti-TNF, <italic>n</italic> = 10) therapy.</p></sec><sec id="ST3"><title>Results</title><p>Among untreated RA patients with active disease (Disease Activity Score 28-C-reactive protein = 5.6 ± 0.89) an expanded population of peripheral GM-CSF+ B (4.1 ± 2.2%) and T (3.4 ± 1.6%) cells was detected compared with both disease (1.7 ± 0.9%, <italic>p</italic> &lt; 0.0001 and 1.7 ± 1.3%, <italic>p</italic> &lt; 0.0001, respectively) and healthy (0.3 ± 0.2%, <italic>p</italic> &lt; 0.0001 and 0.6 ± 0.6%, <italic>p</italic> &lt; 0.0001) controls. RA GM-CSF+ B cells displayed more commonly a plasmablast or transitional phenotype (37.12 ± 18.34% vs. 14.26 ± 9.46%, <italic>p</italic> = 0.001 and 30.49 ± 15.04% vs. 2.45 ± 1.84%, <italic>p</italic> &lt; 0.0001, respectively) and less a memory phenotype (21.46 ± 20.71% vs. 66.99 ± 16.63%, <italic>p</italic> &lt; 0.0001) compared to GM-CSF− cells. GM-CSF expression in RA patients did not correlate to disease duration, activity or serological status. Anti-TNF treatment led to a statistically significant decrease in GM-CSF+ B and T cells while MTX had no significant effect.</p></sec><sec id="ST4"><title>Discussion</title><p>This is the first study showing an expanded population of GM-CSF+ B and T lymphocytes in patients with active RA which declined after anti-TNF therapy.</p></sec>