Serum calgranulin C is a highly sensitive autoinflammation activity indicator in patients with familial periodic fevers

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Aim. To determine the possibility of using the serum proinflammatory calcium-binding protein, or calgranulin C (S100A12), to assess activity and therapeutic efficiency in patients with periodic disease (PD) and other familial periodic fevers (FPFs). Subjects and methods. Thirty-five patients with PD and other FPDs, which were verified by molecular genetic study, were examined. In accordance with the disease activity, the patients were divided into 2 groups. The investigators determined the concentration of S100A12 by solid-phase enzyme immunoassay and that of other acute-phase inflammatory markers (erythrocyte sedimentation rate (ERT), neutrophil counts, and fibrinogen and C-reactive protein (CRP) concentrations). Results. The serum concentration of S100A12 in the stage of disease activity was 466.7 (265.22—851.7) ng/ml, which was significantly higher than in remission (244.29 (118.93—409.85) ng/ml (p=0.000002). The highest S100A12 concentrations were noted in the patients with PD; these were 758.95 (434.80—1035.95) ng/ml; the S100A12 level in the majority of PD patients even during remission remained moderately higher. An investigation of the relationship of A100A12 to genetic variants found no differences between the patients homozygous for M694V and those with other genotypes (p=0.37). Estimation of the time course of therapy-induced changes in the serum S100A12 concentration revealed its considerable reduction (р=0.0018). However, normalization of S100A12 levels was not achieved in PD. The remaining increased S100A12 concentration in these patients may be suggestive of the activity of PD despite the absence of its clinical manifestations. S100A12 as a highly sensitive marker allows more exact evaluation of the anti-inflammatory effect of therapy. The S100A12 identification of the subclinical activity of autoinflammatory diseases made all the more important since traditional inflammatory markers, such as ERT, CRP, fibrinogen, and leukocyte counts, are less sensitive for these purposes. In our study, these markers were within the reference range in remission. No differences were found in the S100A12 levels between the groups with and without amyloidosis (p=0.62). Conclusion. S100A12 is a highly sensitive marker for the activity of autoinflammatory diseases and the efficiency of their therapy. The serum level of S100A12 in PD may be used to diagnose the subclinical activity of inflammation, which is of importance in monitoring the risk of amyloidosis.

Keywords:

autoinflammation

periodic disease

cryopyrinopathies

Muckle-Wells syndrome

NOMID

TRAPS

inflammatory activity

AA-amyloidosis

calgranulin C (S100A12)

Authors:

Bogdanova M.V.

Pervyĭ MGMU im. I.M. Sechenova

Rameev V.V.

Kafedra terapii i profzabolevaniĭ MPF, Pervyĭ MGMU im. I.M. Sechenova Minzdrava Rossii

Kozlovskaia L.V.

Pervyĭ Moskovskiĭ gosudarstvennyĭ meditsinskiĭ universitet im. I.M. Sechenova

Fedorov E.S.

V.A. Nasonova Research Institute of Rheumatology, Moscow, Russia ,

Salugina S.O.

V.A. Nasonova Research Institute of Rheumatology, Moscow, Russia ,

List of references:

French FMF Consortium. A candidate gene for familial Mediterranean fever. Nat Genet. 1997;17(1):25-31. doi:10.1038/ng0997-25.
Ombrello MJ, Kastner DL. Autoinflammation in 2010: expanding clinical spectrum and broadening therapeutic horizons. Nat Rev Rheumatol. 2011;7(2):82-84. doi:10.1038/nrrheum.2010.229.
Kanazawa N. Rare hereditary autoinflammatory disorders: towards an understanding of critical in vivo inflammatory pathways. J Dermatol Sci. 2012;66(3):183-189. doi:10.1016/j.jdermsci.2012.01.004.
Masters SL, Simon A, Aksentijevich I, Kastner DL. Horror autoinflammaticus: the molecular pathophysiology of autoinflammatory disease. Annu Rev Immunol. 2009;27:621-668. doi:10.1146/annurev.immunol.25.022106.141627.
Martinon F, Pétrilli V, Mayor A, Tardivel A, Tschopp J. Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature. 2006;440(7081):237-241. doi:10.1038/nature04516.
Виноградова О.М. Периодическая болезнь. Москва: Медицина; 1973.
Aganna E, Martinon F, Hawkins PN et al. Association of mutations in the NALP3/CIAS1/PYPAF1 gene with a broad phenotype including recurrent fever, cold sensitivity, sensorineural deafness, and AA amyloidosis. Arthritis Rheum. 2002;46(9):2445-2452. doi:10.1002/art.10509.
Aksentijevich I, Galon J, Soares M et al. The tumor-necrosis-factor receptor-associated periodic syndrome: new mutations in TNFRSF1A, ancestral origins, genotype-phenotype studies, and evidence for further genetic heterogeneity of periodic fevers. Am J Hum Genet. 2001;69(2):301-314. doi:10.1086/321976.
Dell’Angelica EC, Schleicher CH, Santomé JA. Primary structure and binding properties of calgranulin C, a novel S100-like calcium-binding protein from pig granulocytes. J Biol Chem. 1994;269(46):28929-28936.
Haley KP, Delgado AG, Piazuelo MB et al. The Human Antimicrobial Protein Calgranulin C Participates in Control of Helicobacter pylori Growth and Regulation of Virulence. Infect Immun. 2015;83(7):2944-2956. doi:10.1128/IAI.00544-15.
Yeh CH, Sturgis L, Haidacher J et al. Requirement for p38 and p44/p42 mitogen-activated protein kinases in RAGE-mediated nuclear factor-kappaB transcriptional activation and cytokine secretion. Diabetes. 2001;50(6):1495-1504. doi:10.2337/diabetes.50.6.1495.
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(4):677-682. doi:10.1136/ard.2009.114363.
Kuemmerle-Deschner JB, Tyrrell PN, Koetter I et al. Efficacy and safety of anakinra therapy in pediatric and adult patients with the autoinflammatory Muckle-Wells syndrome. Arthritis Rheum. 2011;63(3):840-849. doi:10.1002/art.30149.
Foell D, Wittkowski H, Hammerschmidt I et al. Monitoring neutrophil activation in juvenile rheumatoid arthritis by S100A12 serum concentrations. Arthritis Rheum. 2004;50(4):1286-1295. doi:10.1002/art.20125.
Bae C-B, Suh C-H, An J-M et al. Serum S100A12 may be a useful biomarker of disease activity in adult-onset Still’s disease. J Rheumatol. 2014;41(12):2403-2408. doi:10.3899/jrheum.140651.
Hofmann MA, Drury S, Hudson BI et al. RAGE and arthritis: the G82S polymorphism amplifies the inflammatory response. Genes Immun. 2002;3(3):123-135. doi:10.1038/sj.gene.6363861.
Livneh A, Langevitz P, Zemer D et al. Criteria for the diagnosis of familial Mediterranean fever. Arthritis Rheum. 1997;40(10):1879-1885. doi:10.1002/1529-0131(199710)40:10<1879::AID-ART23>3.0.CO;2-M.
Sibley CH, Plass N, Snow J et al. Sustained response and prevention of damage progression in patients with neonatal-onset multisystem inflammatory disease treated with anakinra: a cohort study to determine three- and five-year outcomes. Arthritis Rheum. 2012;64(7):2375-2386. doi:10.1002/art.34409.
Pras E, Livneh A, Balow JE et al. Clinical differences between North African and Iraqi Jews with familial Mediterranean fever. Am J Med Genet. 1998;75(2):216-219. doi:10.1002/(SICI)1096-8628(19980113)75:2<216::AID-AJMG20>3.0.CO;2-R.
Piram M, Koné-Paut I, Lachmann HJ et al. Validation of the auto-inflammatory diseases activity index (AIDAI) for hereditary recurrent fever syndromes. Ann Rheum Dis. 2014;73(12):2168-2173. doi:10.1136/annrheumdis-2013-203666.
Dinarello CA. A clinical perspective of IL-1β as the gatekeeper of inflammation. Eur J Immunol. 2011;41(5):1203-1217. doi:10.1002/eji.201141550.
Mukhin NA, Kozlovskaya LV, Bogdanova MV, Rameev VV, Moiseev SV, Simonyan AK. Predictors of AA amyloidosis in familial Mediterranean fever. Rheumatol Int. 2015;35(7):1257-1261. doi:10.1007/s00296-014-3205-x.
Rameev V, Simonyan A, Sarkisova I, Rameeva A, Kozlovskaya L. Amyloidosis and hereditary periodic autoinflammatory diseases. Klinitsist. 2008;(2):6-15. (In Russ.)
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(4):509-514.
Korkmaz C, Ozdogan H, Kasapçopur O, Yazici H. Acute phase response in familial Mediterranean fever. Ann Rheum Dis. 2002;61(1):79-81. doi:10.1136/ard.61.1.79.
Duzova A, Ozaltin F, Ozon A et al. Bone mineral density in children with familial Mediterranean fever. Clin Rheumatol. 2004;23(3):230-234. doi:10.1007/s10067-004-0874-y.
Yuksel S, Samli H, Colbay M et al. Increased serum osteoprotegerin levels associated with decreased bone mineral density in familial Mediterranean fever. Tohoku J Exp Med. 2009;217(4):321-327.
Ehrenfeld M, Brzezinski A, Levy M, Eliakim M. Fertility and obstetric history in patients with familial Mediterranean fever on long-term colchicine therapy. Br J Obstet Gynaecol. 1987;94(12):1186-1191. doi:10.1111/j.1471-0528.1987.tb02320.x.
Ismajovich B, Zemer D, Revach M, Serr DM, Sohar E. The causes of sterility in females with familial Mediterranean fever. Fertil Steril. 1973;24(11):844-847. doi:10.1097/00006254-197406000-00024.
Ofir D, Levy A, Wiznitzer A, Mazor M, Sheiner E. Familial Mediterranean fever during pregnancy: an independent risk factor for preterm delivery. Eur J Obstet Gynecol Reprod Biol. 2008;141(2):115-118. doi:10.1016/j.ejogrb.2008.07.025.
Caliskan M, Gullu H, Yilmaz S et al. Impaired coronary microvascular function in familial Mediterranean fever. Atherosclerosis. 2007;195(2):e161-e167. doi:10.1016/j.atherosclerosis.2007.06.014.
Tavil Y, Ureten K, Oztürk MA et al. The detailed assessment of left and right ventricular functions by tissue Doppler imaging in patients with familial Mediterranean fever. Clin Rheumatol. 2008;27(2):189-194. doi:10.1007/s10067-007-0676-0.
Akdogan A, Calguneri M, Yavuz B et al. Are familial Mediterranean fever (FMF) patients at increased risk for atherosclerosis? Impaired endothelial function and increased intima media thickness are found in FMF. J Am Coll Cardiol. 2006;48(11):2351-2353. doi:10.1016/j.jacc.2006.09.013.
Yilmaz MI, Demirkaya E, Acikel C et al. Endothelial function in patients with familial Mediterranean fever-related amyloidosis and association with cardiovascular events. Rheumatol Oxf Engl. 2014;53(11):2002-2008. doi:10.1093/rheumatology/keu231.
Bilginer Y, Ozaltin F, Basaran C et al. Evaluation of intima media thickness of the common and internal carotid arteries with inflammatory markers in familial Mediterranean fever as possible predictors for atherosclerosis. Rheumatol Int. 2008;28(12):1211-1216. doi:10.1007/s00296-008-0605-9.
Ugurlu S, Seyahi E, Cetinkaya F, Ozbakir F, Balci H, Ozdogan H. Intima-media thickening in patients with familial Mediterranean fever. Rheumatol Oxf Engl. 2009;48(8):911-915. doi:10.1093/rheumatology/kep131.
Deger SM, Ozturk MA, Demirag MD et al. Health-related quality of life and its associations with mood condition in familial Mediterranean fever patients. Rheumatol Int. 2011;31(5):623-628. doi:10.1007/s00296-009-1334-4.
Gimeno D, Kivimäki M, Brunner EJ et al. Associations of C-reactive protein and interleukin-6 with cognitive symptoms of depression: 12-year follow-up of the Whitehall II study. Psychol Med. 2009;39(3):413-423. doi:10.1017/S0033291708003723.
Kucuk A, Gezer IA, Ucar R, Karahan AY. Familial Mediterranean Fever. Acta Medica Hradec Král Univ Carol Fac Medica Hradec Král. 2014;57(3):97-104. doi:10.14712/18059694.2014.47.
Lachmann HJ, Goodman HJB, Gilbertson JA et al. Natural history and outcome in systemic AA amyloidosis. N Engl J Med. 2007;356(23):2361-2371. doi:10.1056/NEJMoa070265.

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