Restoration of the Immune Balance by Autologous Bone Marrow Transplantation in Juvenile Idiopathic Arthritis

Eveline      Delemarre; Sarah      Roord; Nico      Wulffraat; Femke      van Wijk; Berent      Prakken

doi:10.2174/157488811794480726

Abstract

Juvenile idiopathic arthritis (JIA) is one of the most frequent autoimmune diseases in childhood and is characterized by chronic inflammation of the synovial fluid in joints. Several drugs are available for the treatment of JIA, including various biological agents that interfere with critical cytokine pathways. Though very effective in suppressing disease activity, none of these drugs can cure the disease and induce a lasting medication free remission. A small proportion of JIA patients will become or are unresponsive to any form of medical treatment. For these severely ill patients autologous bone marrow transplantation (aBMT) is a last resort treatment. aBMT is remarkably effective in suppressing disease activity, with beneficial outcome reported in around 70% of these previously refractory patients. Moreover aBMT is the only treatment that can induce a lasting medication-free-disease remission in these patients. In the very long term (after 7 years of remission) however, some disease relapses are observed, with the disease returning in a less severe form compared to prior aBMT. The exact mechanism of how aBMT is inducing this lasting disease remission is still largely unknown, but data from both animal models and humans suggest a prominent role for regulatory T cells.

In this review we reviewed the current views of the cellular mechanisms that lay beneath disease induction of JIA and the disease remission caused by aBMT therapy.

Keywords: Juvenile idiopathic arthritis, autologous bone marrow transplantation, regulatory T cells, T helper 17 cells, autoimmune diseases, synovial fluid, cytokine, rheumatic diseases, arthritis, anorexia, spiking fever, hepatosplenomegaly, non-steroidal anti-inflammatory drugs, disease modifying drugs, anti-interleukin 1, anti-interleukin 6, anti-TNF, CD4, glucocorticoid-induced tumor necrosis factor receptor (GITR), FOXP3, peripheral immune system, im-mune dysregulation, polyendocrinopathy, enterpathy, homeosta-sis, autoimmunity, immunopathogenesis, Experimental Autoimmune Enceohalomyelitis, Multiple Sclerosis (MS), Systemic Lupus Erythematosus, chemotherapy, lymphocytes, macrophage activation syn-drome, Varicella Zoster Virus, Epstein Barr virus, Cytomegalie Virus, disseminated Adenovirus reactivation, corticosteroids, immunobiology, phenotype, proteo-glycan, proteoglycan induced ar-thritis (PGIA), histopathological resemblance, polyarthritis, immune tolerance, white blood cell count (WBC), anti-CD25 monoclonal antibody, immunologi-cal mechanism