Thematic stream: inflammatory arthritis (PP01-PP31): PP01. Autoinflammatory Synovitis in Familial Mediterranean Fever is Characterized by Numerous Neutrophils Lacking Myeloperoxidase and Lysozyme, Macrophages, Mast Cells and B Cells, Up-Regulation of Galectin-1, P65 (REL A)/NF-KB and Inos, but not COX-2

Background: Arthritis in familial Mediterranean fever (FMF) is typically monoarticular, of sudden onset, self-limiting, rarely destructive, and a frequent manifestation of FMF. The mechanisms governing the initiation and resolution of this highly inflammatory disease entity are not fully understood. Therefore, to decipher the complexity of articular autoinflammation, we defined inflammatory cells and some mediators of inflammation and apoptosis in the synovial membrane of a patient with FMF. Methods: A synovial tissue sample obtained from an inflamed hip joint of a boy homozygous for mutation M694I in pyrin/marenostrin was studied by immunohistochemistry using commercially available antibodies specific for tryptase, CD68, CD3, CD20 and CD138. With the same technique, we also analyzed the expression and distribution of myeloperoxidase, lysozyme, galectin-1, galectin-3, p65 (RelA)/NF-κB, iNOS, COX-2 and activated caspase-3. Results: Abundant neutrophils, macrophages and mast cells, but also B cells were observed, which were more numerous than T lymphocytes or plasma cells. Neutrophils had no granules containing myeloperoxidase or lysozyme in their cytoplasm. Galectin-1 was found in many mononuclear cells sparse throughout the synovial tissue, whereas the expression of galectin-3 was less prominent and scattered. Neither of the galectins was detected in neutrophils. p65 (RelA)/NF-κB and iNOS were both up-regulated in most of the inflammatory cells, whereas COX-2 expression was low, and cleaved caspase-3, used as proxy to demonstrate intrinsic apoptosis, was undetectable. Conclusions: The exquisitely inflammatory, yet non-destructive character of FMF arthritis may correlate with the presence of non-pathogenic neutrophils lacking effector molecules and the preferential expression of iNOS and anti-inflammatory galectin-1 in regulatory cells of the innate immune system, most likely in macrophages. Intrinsic apoptosis seemed irrelevant for controlling synovial autoinflammation, but regulation through pyroptosis, mast cells and the adaptive immune system are possible alternatives.