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C reactive protein (CRP), a member of the pentraxin family, is a widely measured acute phase reactant. CRP concentrations have been shown to be increased in familial Mediterranean fever (FMF), which is the most common autoinflammatory disorder around the world.1–3 Interestingly, CRP is not only increased during the attacks of FMF but in between the attacks as well.3 Serum amyloid A protein levels are also increased in these patients.4
We have observed in our paediatric registry of over 1000 patients with FMF that many rheumatic diseases such as vasculitis and juvenile arthritis accompany FMF; we suggested that this might be due to the increased inflammatory milieu in these patients.1 However, none of the patients had systemic lupus erythematosus (SLE). Conversely, none of our patients with SLE had associated FMF.
Again in a multicentre study including about 3000 Turkish patients, certain inflammatory diseases were markedly increased, whereas SLE was not.5
We suggest that this is because of the high levels of CRP in these patients.1 These molecules are known to play an important part in the removal of apoptotic material by binding to the exposed small nuclear ribonucleoprotein (snRNP) particles. CRP mediates the removal of apoptotic cells.6 Defective disposal of the potential autoantigens presented in the apoptotic blebs is a contributory factor in the pathogenesis of SLE. CRP has also been shown to bind to snRNPs.7 Recently, Russell et al have shown that a polymorphism in the CRP gene associated with lower CRP levels was associated with antinuclear antibody formation and they suggested that reduced basal CRP expression predisposes to the development of SLE.8 The rarity of SLE in patients with FMF may yet be further indirect clinical evidence of the role of CRP in protection against autoimmune diseases.
FMF is a very common disease in people of the eastern Mediterranean. Protection against SLE was probably not the selective advantage of the mutated gene; however, the augmented acute phase response seems to offer these patients at least one advantage.