Download PDF
CC BY 4.0 · Journal of Child Science 2021; 11(01): e163-e169
DOI: 10.1055/s-0041-1731303
Original Article

Clinical Implications of S100A12 and Resolvin D1 Serum Levels, and Related Genes in Children with Familial Mediterranean Fever

Zeinab Y. Abdallah
1   Division of Human Genetics and Genome Research, Department of Biochemical Genetics, National Research Centre, Cairo, Egypt
,
Mona Ibrahim
1   Division of Human Genetics and Genome Research, Department of Biochemical Genetics, National Research Centre, Cairo, Egypt
,
Manal M. Thomas 
2   Division of Human Genetics and Genome Research, Department of Clinical Genetics, National Research Centre, Cairo, Egypt
,
Hisham Megahed
2   Division of Human Genetics and Genome Research, Department of Clinical Genetics, National Research Centre, Cairo, Egypt
,
Ghada Nour Eldeen
3   Division of Human Genetics and Genome Research, Department of Molecular Genetics and Enzymology, National Research Centre, Cairo, Egypt
,
Khaled Hamed
2   Division of Human Genetics and Genome Research, Department of Clinical Genetics, National Research Centre, Cairo, Egypt
,
Mohamed Fares
4   Division of Engineering Research, Department of Informatics and Systems, Biomedical Informatics and Chemoinformatics Group, National Research Centre, Cairo, Egypt
5   Division of The Veterinary Medicine, National Research Centre, Cairo, Egypt
,
Mahmoud ElHefnawi
4   Division of Engineering Research, Department of Informatics and Systems, Biomedical Informatics and Chemoinformatics Group, National Research Centre, Cairo, Egypt
,
Hala T. El-Bassyouni 
2   Division of Human Genetics and Genome Research, Department of Clinical Genetics, National Research Centre, Cairo, Egypt
› Author Affiliations Funding None.
› Further Information
   Permissions and Reprints

Abstract

The aim of this article was to study the role of S100A12 and resolvin D1-related genes and serum levels in the diagnosis and detection of subclinical inflammation in children with familial Mediterranean fever (FMF) during the quiescent stage of the disease. Seventy-eight children with FMF during the silent state and 60 healthy control were studied. Serum S100A12 and resolvin D1 were quantitatively measured using enzyme-linked immunosorbent assay. In addition, the levels of C-reactive protein, erythrocyte sedimentation rate, and hemoglobin were determined. The clinical severity was evaluated. The link between the Mediterranean fever (MEFV) gene and the genes related to the two studied biomarkers was also assessed. Correlation between S100A12 and resolvin D1 and the clinical severity was assessed. The mean serum levels of S100A12 and resolvin D1 were 847.4 and 793.3, respectively, which were highly significantly increased (p = 0.001) compared with the controls (324.3 and 235.1, respectively). The receiver operating characteristic curve test showed that S100A12 had a sensitivity of 97.4% and specificity of 80% with cutoff value of 529.5, while resolvin D1 showed a sensitivity of 100% and specificity of 50% with cutoff value of 231.2. A correlation was detected between the clinical severity and S100A12 and resolvin D1. This study delineated that S100A12 and resolvin D1 are sensitive biomarkers to detect the degree of inflammation in children with FMF during the silent period. Consequently, we recommend adjusting the colchicine dose to ameliorate the disease's symptoms and to improve the quality of life in these patients.

Keywords

familial Mediterranean fever - inflammation - MEFV gene - S100A12 protein - resolvin D1


Publication History

Received: 06 February 2021

Accepted: 18 April 2021

Article published online:
26 June 2021

© 2021. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Guler T, Garip Y, Dortbas F, Dogan YP. Quality of life in Turkish patients with familial Mediterranean fever: association with fatigue, psychological status, disease severity and other clinical parameters. Egypt Rheumatol 2018; 40: 117-121
    CrossrefPubMedGoogle Scholar
  • 2 Salah S, Talaat HS, El Basha NR, Marzouk H, Abd Elhamid S, Shafie ES. Comparing D-dimer status in children with familial Mediterranean fever during and in between acute attacks. Egypt Rheumatol 2018; 40: 107-110
    CrossrefPubMedGoogle Scholar
  • 3 Ozen S, Batu ED, Demir S. Familial Mediterranean Fever: recent developments in pathogenesis and new recommendations for management. Review ARTICLE. Front Immunol 2017; •••: 23
    PubMedGoogle Scholar
  • 4 Mohamed R, El-Bassyouni HT, Elwan SH. et al. Carotid intima-media thickness, lipid profile, serum amyloid A and vitamin D status in children with familial Mediterranean fever. Egypt Rheumatol 2020; 42: 237-240
    CrossrefPubMedGoogle Scholar
  • 5 El-Shanti H, Majeed HA, El-Khateeb M. Familial Mediterranean fever in Arabs. Lancet 2006; 367 (9515): 1016-1024
    CrossrefPubMedGoogle Scholar
  • 6 Aksentijevich I, Centola M, Deng Z. et al; The International FMF Consortium. Ancient missense mutations in a new member of the RoRet gene family are likely to cause familial Mediterranean fever. Cell 1997; 90 (04) 797-807
    CrossrefPubMedGoogle Scholar
  • 7 Pietzsch J, Hoppmann S. Human S100A12: a novel key player in inflammation?. Amino Acids 2009; 36 (03) 381-389
    CrossrefPubMedGoogle Scholar
  • 8 Kallinich T, Wittkowski H, Keitzer R, Roth J, Foell D. Neutrophil-derived S100A12 as novel biomarker of inflammation in familial Mediterranean fever. Ann Rheum Dis 2010; 69 (04) 677-682
    CrossrefPubMedGoogle Scholar
  • 9 Kessel C, Holzinger D, Foell D. Phagocyte-derived S100 proteins in autoinflammation: putative role in pathogenesis and usefulness as biomarkers. Clin Immunol 2013; 147 (03) 229-241
    CrossrefPubMedGoogle Scholar
  • 10 Serhan CN, Chiang N. Endogenous pro-resolving and anti-inflammatory lipid mediators: a new pharmacologic genus. Br J Pharmacol 2008; 153 (Suppl. 01) S200-S215
    CrossrefPubMedGoogle Scholar
  • 11 Recchiuti A, Codagnone M, Pierdomenico AM. et al. Immunoresolving actions of oral resolvin D1 include selective regulation of the transcription machinery in resolution-phase mouse macrophages. FASEB J 2014; 28 (07) 3090-3102
    CrossrefPubMedGoogle Scholar
  • 12 Taylan A, Gurler O, Toprak B. et al. S1000A12, Chitotriosidase, and resolvin D1 as potential biomarkers of familial Mediterranean fever. J Korean Med Sci 2015; 30 (09) 1241-1245
    CrossrefPubMedGoogle Scholar
  • 13 Marzouka H, Mostafa N, Khalifa I, Badawi N. Effect of an increased dose of colchicine on microalbuminuria in children with familial Mediterranean Fever. Egypt Rheumatol 2020; 42: 141-145
    CrossrefPubMedGoogle Scholar
  • 14 Kisla Ekinci RM, Balci S, Dogruel D, Altintas DU, Yilmaz M. Canakinumab in children with familial Mediterranean fever: a single-center, retrospective analysis. Paediatr Drugs 2019; 21 (05) 389-395
    CrossrefPubMedGoogle Scholar
  • 15 Pras E, Livneh A, Balow Jr JE. et al. Clinical differences between North African and Iraqi Jews with familial Mediterranean fever. Am J Med Genet 1998; 75 (02) 216-219
    CrossrefPubMedGoogle Scholar
  • 16 Ozen S, Aktay N, Lainka E, Duzova A, Bakkaloglu A, Kallinich T. Disease severity in children and adolescents with familial Mediterranean fever: a comparative study to explore environmental effects on a monogenic disease. Ann Rheum Dis 2009; 68 (02) 246-248
    CrossrefPubMedGoogle Scholar
  • 17 Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988; 16 (03) 1215
    CrossrefPubMedGoogle Scholar
  • 18 Zarouk WA, El-Bassyouni HT, Ramadan A. et al. Screening of the most common MEFV mutations in a large cohort of Egyptian patients with familial Mediterranean fever. Gen Rep. 2018; 11: 23-28
    PubMedGoogle Scholar
  • 19 Mejtoute T, Sayel H, El-Akhal J. et al. The detection of a novel insertion mutation in exon 2 of the MEFV gene associated with familial Mediterranean fever in a Moroccan family. Hum Genome Var 2017; 4: 17023
    CrossrefPubMedGoogle Scholar
  • 20 Warde-Farley D, Donaldson SL, Comes O. et al. The GeneMANIA prediction server: biological network integration for gene prioritization and predicting gene function. Nucleic Acids Res 2010; 38 (Web Server issue): W214-20
    CrossrefPubMedGoogle Scholar
  • 21 Pandurangan AP, Ochoa-Montaño B, Ascher DB, Blundell TL. SDM: a server for predicting effects of mutations on protein stability. Nucleic Acids Res 2017; 45 (W1): W229-W235
    CrossrefPubMedGoogle Scholar
  • 22 Wittkowski H, Frosch M, Wulffraat N. et al. S100A12 is a novel molecular marker differentiating systemic-onset juvenile idiopathic arthritis from other causes of fever of unknown origin. Arthritis Rheum 2008; 58 (12) 3924-3931
    CrossrefPubMedGoogle Scholar
  • 23 Gohar F, Orak B, Kallinich T. et al. Correlation of secretory activity of neutrophils with genotype in patients with familial Mediterranean fever. Arthritis Rheumatol 2016; 68 (12) 3010-3022
    CrossrefPubMedGoogle Scholar
  • 24 Ben-Zvi I, Livneh A. Chronic inflammation in FMF: markers, risk factors, outcomes and therapy. Nat Rev Rheumatol 2011; 7 (02) 105-112
    CrossrefPubMedGoogle Scholar
  • 25 Serhan CN. Novel lipid mediators and resolution mechanisms in acute inflammation: to resolve or not?. Am J Pathol 2010; 177 (04) 1576-1591
    CrossrefPubMedGoogle Scholar
  • 26 Ozen S, Uckan D, Baskin E. et al. Increased neutrophil apoptosis during attacks of familial Mediterranean fever. Clin Exp Rheumatol 2001; 19 (05, Suppl 24): S68-S71
    PubMedGoogle Scholar
  • 27 Kholoussi S, Kholoussi N, Zaki ME. et al. Immunological evaluation in patients with familial Mediterranean fever. Open Access Maced J Med Sci 2018; 6 (02) 310-313
    CrossrefPubMedGoogle Scholar
  • 28 Lofty HM, Marzouk H, Farag Y. et al. Serum amyloid A level in Egyptian children with familial Mediterranean fever. Int J Rheumatol 2016; 7354018
    PubMedGoogle Scholar
  • 29 Duzova A, Bakkaloglu A, Besbas N. et al. Role of A-SAA in monitoring subclinical inflammation and in colchicine dosage in familial Mediterranean fever. Clin Exp Rheumatol 2003; 21 (04) 509-514
    PubMedGoogle Scholar
  • 30 Lachmann HJ, Sengül B, Yavuzşen TU. et al. Clinical and subclinical inflammation in patients with familial Mediterranean fever and in heterozygous carriers of MEFV mutations. Rheumatology (Oxford) 2006; 45 (06) 746-750
    CrossrefPubMedGoogle Scholar
  • 31 Berkun Y, Padeh S, Reichman B. et al. A single testing of serum amyloid a levels as a tool for diagnosis and treatment dilemmas in familial Mediterranean fever. Semin Arthritis Rheum 2007; 37 (03) 182-188
    CrossrefPubMedGoogle Scholar
  • 32 Korkmaz C, Ozdogan H, Kasapçopur O, Yazici H. Acute phase response in familial Mediterranean fever. Ann Rheum Dis 2002; 61 (01) 79-81
    CrossrefPubMedGoogle Scholar