Comment on: Dysregulated mature IL-1β production in familial Mediterranean fever: reply

Kiyoshi Migita, Yoshika Tsuji, Tadashi Nakamura
2015 Rheumatology  
Comment on: Dysregulated mature IL-1 production in familial Mediterranean fever: reply SIR, We thank Drs Dogan and Agilli for their interest and valuable comments [1] on our recent publication [2] . Serum amyloid A (SAA), an acute phase reactant, and its induction require IL-6 and either IL-1 or TNF-a [3]. SAA is a more sensitive biomarker than CRP that is elevated in response to cardiovascular diseases, which results from a phenomenon known as subclinical vascular inflammation [4].
more » ... on [4]. Furthermore, SAA levels can be influenced by various factors including smoking, diabetes and the use of medications. Circulating SAA levels, which reflect the degree of subclinical inflammation, can fluctuate, but are normally <20 g/ml [4]. However, levels of SAA increase by as much as 1000-fold above baseline levels in cases of both acute inflammation and inflammatory disorders, including autoinflammatory disease and RA, in response to inflammatory cytokines [5]. Consequently, measurements of SAA levels can be imprecise and sometimes misleading without considering these wide ranges. It is possible that the subclinical inflammation that accompanies smoking or metabolic diseases influences SAA levels in FMF patients during an attack-free phase. However, the contribution of subclinical inflammation to the magnitude of SAA elevation is predicted to be minimal during moderate inflammatory phases. It has also been reported that substantial subclinical inflammation occurs widely and over prolonged periods of time (including during the attack phase) in patients with FMF [6]. Furthermore, basal and peak acute phase SAA concentrations are even greater in individuals with MEFV mutations [7]. In contrast, SAA levels were always markedly elevated during symptomatic attacks of FMF. The SAA levels were shown to be massively elevated during the acute inflammatory phase (attack phase), with median values of 633 g/ml (range 1401330) in FMF patients [7]. Similarly, the concentrations of SAA in patients with active RA were markedly elevated [420 g/ml (S.D. 96)] [8], and these values were significantly higher than those in individuals without inflammatory disorders [8]. We measured circulating SAA levels in a few FMF patients during the attack-free phase or in RA patients without active disease activity. However, most of these patients still have substantial ongoing inflammation. Thus subclinical inflammation caused by such accompanying co-morbidities may affect circulating SAA levels; but based on our measurements, these effects are predicted to be marginal in our subjects.
doi:10.1093/rheumatology/kev333 pmid:26342223 fatcat:njrnx6mtbzdofifetp7z3mdcei