Lack of Correlation between Amyloid a Protein Levels and Clinical Parameters in Aspirated Fat Tissue of Familial Mediterranean Fever Patients with Secondary Amyloidosis

Familial Mediterranean fever (FMF) is the most frequent autoinflammatory disorder characterized by short, repeated, and self-limiting crises of fever and serositis. The disease was described as autosomal recessive hereditary transmission secondary to variants of the MEFV (MEditerranean FeVer) gene, even though a variable proportion of patients only present a heterozygous variant. FMF is very common in certain ethnic groups (Turkish, Armenian, Arab, and Jewish), even though it has been described throughout the Mediterranean and elsewhere in the world. The clinical manifestations are variable, with secondary amyloidosis being the most serious complication of the disorder. Treatment and prophylaxis are mainly based on the administration of colchicine, which prevents the crises and avoids complications in most cases. This study reviews the course of seven pediatric patients diagnosed with FMF during the period 2010–2018 at a district hospital. Most of the patients were of Caucasian origin, with onset at an early age in the form of fever as the main symptom, and some patients moreover presented less frequent manifestations (pericardial effusion, sensorineural hearing loss). Two cases presented plasmatic amyloid A protein elevation that subsided with the treatment. All the patients initially received colchicine, and one of them required prescription of anakinra, which was replaced by canakinumab due to a serious adverse reaction. There were no cases of consanguinity, and all the patients were of Mediterranean origin. The subjects showed a favorable course over the years, which was attributed to the early diagnosis and treatment provided.

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POS0073 ASSOCIATION OF SAA1 GENE POLYMORPHISM -13T/C (RS12218) WITH CRYOPYRIN ASSOCIATED PERIODIC SYNDROMES (CAPS), BUT NOT FAMILIAL MEDITERRANEAN FEVER (FMF)

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.3910 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 243.2-243

Author(s):

I. Guseva ◽

E. Fedorov ◽

S. Salugina ◽

M. Krylov ◽

E. Samarkina

Keyword(s):

Familial Mediterranean Fever ◽

Gene Polymorphism ◽

Protein Concentration ◽

Clinical Symptoms ◽

Clinical Signs ◽

Compound Heterozygous ◽

Protein Levels ◽

Amyloid A ◽

Significant Difference ◽

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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Amyloidosis and Glomerular Diseases in Familial Mediterranean Fever

Medicina ◽

10.3390/medicina57101049 ◽

2021 ◽

Vol 57 (10) ◽

pp. 1049

Author(s):

Rossella Siligato ◽

Guido Gembillo ◽

Vincenzo Calabrese ◽

Giovanni Conti ◽

Domenico Santoro

Keyword(s):

Nephrotic Syndrome ◽

Familial Mediterranean Fever ◽

Periodic Fever ◽

Rapid Progression ◽

Secondary Amyloidosis ◽

Aa Amyloidosis ◽

Glomerular Diseases ◽

Amyloid A ◽

Serum Amyloid A Protein ◽

Mediterranean Fever

Familial Mediterranean fever (FMF) is a genetic autoinflammatory disease with autosomal recessive transmission, characterized by periodic fever attacks with self-limited serositis. Secondary amyloidosis due to amyloid A renal deposition represents the most fearsome complication in up to 8.6% of patients. Amyloidosis A typically reveals a nephrotic syndrome with a rapid progression to end-stage kidney disease still. It may also involve the cardiovascular system, the gastrointestinal tract and the central nervous system. Other glomerulonephritis may equally affect FMF patients, including vasculitis such as IgA vasculitis and polyarteritis nodosa. A differential diagnosis among different primary and secondary causes of nephrotic syndrome is mandatory to determine the right therapeutic choice for the patients. Early detection of microalbuminuria is the first signal of kidney impairment in FMF, but new markers such as Neutrophil Gelatinase-Associated Lipocalin (NGAL) may radically change renal outcomes. Serum amyloid A protein (SAA) is currently considered a reliable indicator of subclinical inflammation and compliance to therapy. According to new evidence, SAA may also have an active pathogenic role in the regulation of NALP3 inflammasome activity as well as being a predictor of the clinical course of AA amyloidosis. Beyond colchicine, new monoclonal antibodies such as IL-1 inhibitors anakinra and canakinumab, and anti-IL-6 tocilizumab may represent a key in optimizing FMF treatment and prevention or control of AA amyloidosis.

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Familial Mediterranean Fever: an unusual cause of liver disease

Italian Journal of Pediatrics ◽

10.1186/s13052-019-0712-0 ◽

2019 ◽

Vol 45 (1) ◽

Cited By ~ 1

Author(s):

Maria Cristina Maggio ◽

Maria Castiglia ◽

Giovanni Corsello

Keyword(s):

Abdominal Pain ◽

Liver Disease ◽

Familial Mediterranean Fever ◽

Serum Amyloid A ◽

Mefv Gene ◽

Serum Amyloid ◽

Aphthous Stomatitis ◽

Homozygous Mutation ◽

Amyloid A ◽

Mediterranean Fever

Abstract Background Familial Mediterranean Fever is an autoinflammatory disease typically expressed with recurrent attacks of fever, serositis, aphthous stomatitis, rash. Only a few reports describe the association with hepatic involvement. Case presentation We describe the clinical case of a child affected, since the age of 1 year, by recurrent fever, aphthous stomatitis, rash, arthralgia, associated with abdominal pain, vomiting, lymphadenopathy. The diagnosis of Familial Mediterranean Fever was confirmed by the genetic study of MEFV gene; the homozygous mutation M694 V in exon was documented. A partial control of attacks was obtained with colchicine. The child continued to manifest only recurrent episodes of abdominal pain without fever, however serum amyloid A persisted high, in association with enhanced levels of CRP, AST and ALT (1.5 x n.v.). The dosage of colchicine was increased step by step and the patient achieved a better control of symptoms and biochemical parameters. However, the patient frequently needed an increase in the dose of colchicine, suggesting the possible usefulness of anti-interleukin-1 beta treatment. Conclusions The unusual presentation of Familial Mediterranean Fever with liver disease suggests the role of inflammasome in hepatic inflammation. Colchicine controls systemic inflammation in most of the patients; however, subclinical inflammation can persist in some of them and can manifest with increased levels of CRP, ESR, serum amyloid A also in attack-free intervals.

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