Novel Protagonists in Autoinflammatory Arthritis of Familial Mediterranean Fever

To clarify mechanisms responsible for the self-limiting and nonerosive features of autoinflammatory joint disease in familial Mediterranean fever (FMF), we performed a study on synovial tissue obtained surgically from an acutely inflamed hip joint from a boy feared to have septic arthritis but later found to be homozygous for mutation M694I in pyrin/marenostrin. We defined by immunohistology the infiltrating cells and examined the in situ expression of plausible protagonists in synovitis of FMF: myeloperoxidase, lysozyme, galectin 1, galectin 3, p65 (RelA)/nuclear factor kappa B, inducible nitric-oxide synthase, cyclooxygenase 2, and cleaved caspase 3. Neutrophils deficient in myeloperoxidase and lysozyme, macrophages, and mast cells outnumbered T and B lymphocytes as well as plasma cells. Among cells of adaptive immunity, B lymphocytes were predominant. Galectin 1 was detected in numerous cells of the innate immune system throughout the synovial tissue, whereas expression of galectin 3 was less abundant and scattered. p65 (RelA)/nuclear factor kappa B and inducible nitric-oxide synthase were both upregulated in most of the infiltrating cells. Cyclooxygenase 2 expression was low, and cleaved caspase 3 was undetectable. We conclude that the exquisitely inflammatory yet nondestructive character of FMF arthritis could correlate with the presence of nonpathogenic neutrophils lacking effector molecules and the widespread expression of anti-inflammatory galectin 1 in regulatory cells of the innate immune system. Intrinsic apoptosis seemed irrelevant for confining synovial autoinflammation, but regulation through pyroptosis or the adaptive immune system remains possible. Pediatrics 2011;128:e464-e470