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Macrophage function changes following rituximab treatment in patients with rheumatoid arthritis
  1. E Toubi (elias.toubi{at}b-zion.org.il)
  1. Division of Clinical Immunology and Allergy, Bnai Zion Medical Center, Technion, Haifa, Israel
    1. A Kessel
    1. Division of Clinical Immunology and Allergy, Bnai Zion Medical Center, Technion, Haifa, Israel
      1. G Slobodin
      1. Rheumatology Unit,Bnai Zion Medical Center, Technion, Haifa, Israel
        1. N Boulman
        1. Rheumatology Unit,Bnai Zion Medical Center, Technion, Haifa, Israel
          1. E Pavlotzky
          1. Division of Clinical Immunology and Allergy, Bnai Zion Medical Center, Technion, Haifa, Israel
            1. D Zisman
            1. Rheumatology Unit,Bnai Zion Medical Center, Technion, Haifa, Israel
              1. M Rozenbaum
              1. Rheumatology Unit,Bnai Zion Medical Center, Technion, Haifa, Israel
                1. I Rosner
                1. Rheumatology Unit,Bnai Zion Medical Center, Technion, Haifa, Israel

                  Abstract

                  Objective: To assess changes in macrophage phenotype and function following rituximab-induced B cell depletion in rheumatoid arthritis (RA) patients.

                  Patients: Ten patients suffering from RA were treated with rituximab achieving significant B cell depletion four months later. Clinical improvement, rheumatoid factor [RF], anti-cyclic citrullinated peptide [anti-CCP] antibodies, mRNA of BAFF, IL10 and CD86 in human monocyte derived macrophages (HMDM) and TNF-á secretion from cultured HMDM were assessed at baseline and following depletion.

                  Results: A clinical response of ACR 50 was noted in six patients, and another 2 patients responded with moderate improvement, equivalent to ACR 20-50. RF and anti-CCP antibodies were positive at baseline in seven out of ten patients. Four months following therapy, RF disappeared or declined in 6 patients, correlating with clinical improvement. In contrast, anti-CCP remained unchanged in six. Following rituximab treatment, and in association with clinical improvement, BAFF, IL-10, and CD86 mRNA expression in HMDM, was significantly up- regulated compared with values at baseline. A significant decrease in TNF-á in the supernatant of cultured HMDM was also noted.

                  Conclusions: In addition to B cell depletion and attenuation in some of the specific autoantibodies, clinical improvement in rituximab treated RA patients occurred in association with macrophage function changes.

                  • B cells
                  • macrophages
                  • rheumatoid arthritis
                  • rituximab

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