| Popis: |
Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease of the connective tissue preferentially involving joints. It is considered an autoimmune disease. Autoantibodies against immunoglobulins, so called rheumatoid factors, are detected in 80% of the patients. The etiology of the disease is unknown. An interesting association to different HLA types is observed. An overview about pathology and pathogenesis of the arthritis is given. After an initial vasculitis the synovial membrane is colonised by T and B cells. Among the more frequent T cells more CD4+ cells than CD8+ cells are found. Additionally activated cytotoxic T cells and NK cells are present. Migration of the lymphocytes is realised by adhesion molecules. By homing of lymphocytes the synovial membrane is structurally transformed an appears morphologically like a secondary immunoorgan. Enhanced pathogenic humoral and cellular immune responses are going on influenced by activated CD4+ cells associated with macrophages via MHC class II molecules. Rheumatoid factors and antibodies against type II collagen are produced, cytotoxic immune complexes are formed. Cellular interactions induce the expression of proinflammatory cytokines and growth factors, the so called pannus is formed. Aggressiveness of the pannus depends on the HLA pattern. T cell rich synovial tissue is positive for HLA-DR4 in 70% of the cases. Only 15% of B cell rich membranes show this HLA type. The T cell rich type shows a high aggressiveness. Pannus destroys articular cartilage and subchondral bone. Cells at the invasion site of the pannus are classified differently. The majority of the investigators characterizes them as macrophages others as activated fibroblasts. The latter opinion is supported by experiments done in SCID mice. RA is characterized by three pathogenic mechanisms: 1. chronic inflammation of the synovial membrane, 2. enhanced pathogenic T and B cell dependent immunoreactions including autoimmune phenomenons, 3. hyperplasia of synovial tissue. Which mechanisms is on the beginning and induces the others consecutively is an open question. Macrophages and CD4+ cells associated via MHC class II molecules play a central role in the pathogenesis of RA. |
