Evaluation of S100A12 protein levels in children with Familial Mediterranean Fever

Background:Autoinflammatory diseases (AIDs) are a group of rare, genetically determined diseases characterized by a periodic events of inflammation, fever, and clinical symptoms that mimic rheumatic pathology. Laboratory serological markers of AIDs are C reactive protein (CRP) and serum amyloid A (SAA) protein.Objectives:We investigated whether SAA1 gene polymorphism -13T/C (rs12218) may affect the susceptibility to pediatric FMF and CAPS patients (pts). We also evaluate whether this polymorphism can affect CRP and SAA protein levels.Methods:26 FMF pts - 8 boys, 18 girls; age - M(SD) 7.37(5.32) years and 24 CAPS pts - 12 girls, 12 boys; age – 4.76(5.83) years, and 95 healthy individuals (controls) were included in this study. The diagnosis of FMF was based on Turkish paediatric criteria for the diagnosis of familial Mediterranean fever [1] and was confirmed by the detection of pathogenic mutations of the MEFV gene in the homozygous or compound-heterozygous states. The diagnose of CAPS was made on the basis of characteristic clinical signs and was confirmed by the detection of a pathogenic mutation in the NLRP3 gene. SAA1 gene polymorphism -13T/C was genotyped using allele-specific RT-PCR assay. SAA protein concentration was measured using nephelometry in FMF and CAPS pts.Results:Table 1 shows the genotypic and allelic frequencies of SSA1 gene in FMF, CAPS and controls. There were no significant differences between FMF pts and controls in the genotypic and allelic distributions of -13T/C gene polymorphism. The frequency of -13C allele was significantly higher in CAPS pts compared with controls (OR=2.03 [CI 1.02-4.03], p=0.03). Moreover, a statistically significant difference was revealed in the genotypic and allelic distributions between FMF and CAPS pts groups (p=0.047 and p=0.02 respectively). The CRP levels did not correlate with SAA1 - 13T/C polymorphism. The SAA protein concentration was associated with SAA1 gene polymorphism in FMF pts (p=0.036).Table 1.The distribution of genotypes and alleles of SAA1 gene polymorphism -13T/C in FMF, CAPS and control groups.Genotypes/AllelesFMFn=26 (%)CAPSn=24 (%)Controlsn=95 (%)TT12 (46,2)4 (16,7)39 (41,1)TC12 (46,2)14 (58,3)42 (44,2)CC2 (7,7)6 (25,0)14 (14,7)P (pts vs controls)>0,05>0,08T24 (63,2)21 (50,0)80 (61,5)C14 (36,8)21 (50,0)50 (38,5)P (pts vs controls)>0,050.03Conclusion:Our preliminary study in small groups of pediatric FMF and CAPS pts revealed that SAA1 gene polymorphism -13T/C (rs12218) is associated with susceptibility to CAPS, but not FMF. The influence of this polymorphism on SAA protein levels in FMF pts was also shown. Further investigations are required to clarify the role of SAA1 gene polymorphism -13T/C in susceptibility to FMF and CAPS in large studies in different ethnic and population groups.References:[1]Yalcinkaya F, Ozen S, Ozcakar ZB, et al. Rheumatology (Oxford). 2009,48(4): 395-8. doi: 10.1093/rheumatology/ken509.Disclosure of Interests:None declared.

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Anti-Interleukin 1 Treatment for Patients with Familial Mediterranean Fever Resistant to Colchicine: Table 1.

The Journal of Rheumatology ◽

10.3899/jrheum.100718 ◽

2010 ◽

Vol 38 (3) ◽

pp. 516-518 ◽

Cited By ~ 94

Author(s):

SEZA ÖZEN ◽

YELDA BILGINER ◽

NURAY AKTAY AYAZ ◽

MERAL CALGUNERI

Keyword(s):

Familial Mediterranean Fever ◽

Acute Phase ◽

Interleukin 1 ◽

Acute Phase Reactants ◽

Laboratory Findings ◽

Protein Levels ◽

Reactive Protein ◽

Small Series ◽

Mediterranean Fever ◽

Colchicine Therapy

Objective.Familial Mediterranean fever (FMF) is a recessively inherited autoinflammatory disorder characterized by recurrent attacks of fever and serositis. Although colchicine is the standard therapy for preventing attacks and suppressing inflammation, 5%–10% of compliant patients are colchicine-resistant. We report the effect of anti-tumor necrosis factor therapy (etanercept) and anti-interleukin 1 (IL-1) treatment (anakinra) in 6 cases resistant to colchicine therapy.Methods.Five children and an adult patient (3 female, 3 male) who were experiencing at least 2 attacks per month and had consistently elevated C-reactive protein levels despite regular colchicine therapy were given either etanercept or anakinra.Results.Although etanercept lowered the number of attacks (from 3–4 attacks per month to 2 attacks per month), attacks still recurred and acute-phase reactants remained high in 2 patients; thus etanercept was considered ineffective. All 4 patients were switched to anakinra. In 2 patients anakinra completely resolved clinical and laboratory findings. The other 4 patients have been switched to anakinra recently; to date anakinra has reduced the number of attacks (to < 1 per month) and lowered the levels of acute-phase reactants.Conclusion.In this small series, anakinra was succesful in suppressing inflammation and decreasing the number of attacks in FMF. This may be explained by the role of pyrin in the regulation of IL-1ß activation.

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