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Arthritis Research & Therapy
Published in: Arthritis Research & Therapy 1/2020

01-12-2020 | Systemic Lupus Erythematosus | Research article

Higher interferon score and normal complement levels may identify a distinct clinical subset in children with systemic lupus erythematosus

Authors: Alessandra Tesser, Luciana Martins de Carvalho, Paula Sandrin-Garcia, Alessia Pin, Serena Pastore, Andrea Taddio, Luciana Rodrigues Roberti, Rosane Gomes de Paula Queiroz, Virginia Paes Leme Ferriani, Sergio Crovella, Alberto Tommasini

Published in: Arthritis Research & Therapy | Issue 1/2020

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Abstract

Background

Systemic lupus erythematosus (SLE) is a complex multi-system disease, characterized by both autoimmune and autoinflammatory clinical and laboratory features. The role of type I interferon (IFN) in SLE has been demonstrated from the 2000s, by gene expression analyses showing significant over-expression of genes related to type I IFN signalling pathway (IFN signature). However, several studies questioned the role of measuring the intensity of IFN signature (IFN score) to chase SLE activity.
We would assess if the IFN signature can help the clinical and therapeutic stratification of patients with pediatric SLE.

Methods

We measured the IFN score in peripheral whole blood from a series of subjects with childhood-onset SLE and correlated the results with clinical and laboratory parameters.

Results

Thirty-one subjects were included in the study, among which the 87% displayed a positive IFN score. The only significant relation was found for high IFN score in subjects with normocomplementemia. No correlation was observed between IFN score and SLEDAI-2K, BILAG-2004 and SLICC. Patients with high IFN score and normal complement levels also presented lower anti-dsDNA antibodies.

Conclusions

The integration between IFN signature analysis and complement levels may easily distinguish two groups of subjects, in which the autoimmune or autoinflammatory component of the disease seems to be prevalent.
Literature
1.
2.
3.
Silva CA, Avcin T, Brunner HI. Taxonomy for systemic lupus erythematosus with onset before adulthood. Arthritis Care Res (Hoboken). 2012;64(12):1787–93.CrossRef
4.
Malattia C, Martini A. Paediatric-onset systemic lupus erythematosus. Best Pract Res Clin Rheumatol. 2013;27(3):351–62.PubMedCrossRef
5.
Tarr T, Dérfalvi B, Győri N, Szántó A, Siminszky Z, Malik A, et al. Similarities and differences between pediatric and adult patients with systemic lupus erythematosus. Lupus. 2015;24(8):796–803.PubMedCrossRef
6.
Yasutomo K, Horiuchi T, Kagami S, Tsukamoto H, Hashimura C, Urushihara M, et al. Mutation of DNASE1 in people with systemic lupus erythematosus. Nat Genet. 2001;28(4):313–4.PubMedCrossRef
7.
Muñoz LE, Lauber K, Schiller M, Manfredi AA, Herrmann M. The role of defective clearance of apoptotic cells in systemic autoimmunity. Nat Rev Rheumatol. 2010;6(5):280–9.PubMedCrossRef
8.
9.
10.
Tsokos GC, Lo MS, Costa Reis P, Sullivan KE. New insights into the immunopathogenesis of systemic lupus erythematosus. Nat Rev Rheumatol. 2016;12(12):716–30.PubMedCrossRef
11.
12.
Rodero MP, Tesser A, Bartok E, Rice GI, Della Mina E, Depp M, et al. Type i interferon-mediated autoinflammation due to DNASE II deficiency. Nat Commun. 2017;8(1):2176.PubMedPubMedCentralCrossRef
13.
Hooks JJ, Moutsopoulos HM, Geis SA, Stahl NI, Decker JL, Notkins AL. Immune interferon in the circulation of patients with autoimmune disease. N Engl J Med. 1979;301(1):5–8.PubMedCrossRef
14.
Kim T, Kanayama Y, Negoro N, Okamura M, Takeda T, Inoue T. Serum levels of interferons in patients with systemic lupus erythematosus. Clin Exp Immunol. 1987;70(3):562–9.PubMedPubMedCentral
15.
Vallin H, Blomberg S, Alm GV, Cederblad B, Rönnblom L. Patients with systemic lupus erythematosus (SLE) have a circulating inducer of interferon-alpha (IFN-alpha) production acting on leucocytes resembling immature dendritic cells. Clin Exp Immunol. 1999;115(1):196–202.PubMedPubMedCentralCrossRef
16.
Farkas L, Beiske K, Lund-Johansen F, Brandtzaeg P, Jahnsen FL. Plasmacytoid dendritic cells (natural interferon-alpha/beta-producing cells) accumulate in cutaneous lupus erythematosus lesions. Am J Pathol. 2001;159(1):237–43.PubMedPubMedCentralCrossRef
17.
Nzeusseu Toukap A, Galant C, Theate I, Maudoux AL, Lories RJ, Houssiau FA, et al. Identification of distinct gene expression profiles in the synovium of patients with systemic lupus erythematosus. Arthritis Rheum. 2007;56(5):1579–88.PubMedCrossRef
18.
Baechler EC, Batliwalla FM, Karypis G, Gaffney PM, Ortmann WA, Espe KJ, et al. Interferon-inducible gene expression signature in peripheral blood cells of patients with severe lupus. Proc Natl Acad Sci U S A. 2003;100(5):2610–5.PubMedPubMedCentralCrossRef
19.
Bennett L, Palucka AK, Arce E, Cantrell V, Borvak J, Banchereau J, et al. Interferon and granulopoiesis signatures in systemic lupus erythematosus blood. J Exp Med. 2003;197(6):711–23.PubMedPubMedCentralCrossRef
20.
Yao Y, Higgs BW, Morehouse C, de Los RM, Trigona W, Brohawn P, et al. Development of potential pharmacodynamic and diagnostic markers for anti-ifn-α monoclonal antibody trials in systemic lupus erythematosus. Hum Genomics Proteomics. 2009;2009.
21.
Crow YJ, Black DN, Ali M, Bond J, Jackson AP, Lefson M, et al. Cree encephalitis is allelic with Aicardi-Goutiéres syndrome: implications for the pathogenesis of disorders of interferon alpha metabolism. J Med Genet. 2003;40(3):183–7.PubMedPubMedCentralCrossRef
22.
Crow YJ. Type i interferonopathies: a novel set of inborn errors of immunity. Ann N Y Acad Sci. 2011;1238:91–8.PubMedCrossRef
23.
Rice GI, Forte GM, Szynkiewicz M, Chase DS, Aeby A, Abdel-Hamid MS, et al. Assessment of interferon-related biomarkers in aicardi-goutières syndrome associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, and ADAR: a case-control study. Lancet Neurol. 2013;12(12):1159–69.PubMedPubMedCentralCrossRef
24.
Rice GI, Melki I, Frémond ML, Briggs TA, Rodero MP, Kitabayashi N, et al. Assessment of type i interferon signaling in pediatric inflammatory disease. J Clin Immunol. 2017;37(2):123–32.PubMedCrossRef
25.
Kim H, de Jesus AA, Brooks SR, Liu Y, Huang Y, VanTries R, et al. Development of a validated interferon score using nanostring technology. J Interf Cytokine Res. 2018;38(4):171–85.CrossRef
26.
Kirou KA, Lee C, George S, Louca K, Peterson MG, Crow MK. Activation of the interferon-alpha pathway identifies a subgroup of systemic lupus erythematosus patients with distinct serologic features and active disease. Arthritis Rheum. 2005;52(5):1491–503.PubMedCrossRef
27.
Landolt-Marticorena C, Bonventi G, Lubovich A, Ferguson C, Unnithan T, Su J, et al. Lack of association between the interferon-alpha signature and longitudinal changes in disease activity in systemic lupus erythematosus. Ann Rheum Dis. 2009;68(9):1440–6.PubMedCrossRef
28.
Petri M, Fu W, Ranger A, Allaire N, Cullen P, Magder LS, et al. Association between changes in gene signatures expression and disease activity among patients with systemic lupus erythematosus. BMC Med Genet. 2019;12(1):4.
29.
Ting TV, Barnett K, Lynch-Jordan A, Whitacre C, Henrickson M, Kashikar-Zuck S. 2010 American College of Rheumatology adult fibromyalgia criteria for use in an adolescent female population with juvenile fibromyalgia. J Pediatr. 2016;169:181–7 e1.PubMedCrossRef
30.
Hochberg MC. Updating the american college of rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1997;40(9):1725.PubMedCrossRef
31.
Petri M, Orbai AM, Alarcón GS, Gordon C, Merrill JT, Fortin PR, et al. Derivation and validation of the systemic lupus international collaborating clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum. 2012;64(8):2677–86.PubMedPubMedCentralCrossRef
32.
Gladman DD, Ibañez D, Urowitz MB. Systemic lupus erythematosus disease activity index 2000. J Rheumatol. 2002;29(2):288–91.PubMed
33.
Marks SD, Pilkington C, Woo P, Dillon MJ. The use of the British Isles Lupus Assessment Group (BILAG) index as a valid tool in assessing disease activity in childhood-onset systemic lupus erythematosus. Rheumatology (Oxford). 2004;43(9):1186–9.CrossRef
34.
Gladman D, Ginzler E, Goldsmith C, Fortin P, Liang M, Urowitz M, et al. The development and initial validation of the systemic lupus international collaborating clinics/American College Of Rheumatology damage index for systemic lupus erythematosus. Arthritis Rheum. 1996;39(3):363–9.PubMedCrossRef
35.
Castrejón I, Tani C, Jolly M, Huang A, Mosca M. Indices to assess patients with systemic lupus erythematosus in clinical trials, long-term observational studies, and clinical care. Clin Exp Rheumatol. 2014;32(5 Suppl 85):S-85–95.
36.
Pin A, Monasta L, Taddio A, Piscianz E, Tommasini A, Tesser A. An easy and reliable strategy for making type I interferon signature analysis comparable among research centers. Diagnostics (Basel). 2019;9(3):113.CrossRef
37.
Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(−delta delta c(t)) method. Methods. 2001;25(4):402–8.PubMedCrossRef
38.
Hartigan JAaMAW. Algorithm as 136: A k-means clustering algorithm. Journal of the Royal Statistical Society. Series C (Applied Statistics). United Kingdom: Wiley for the Royal Statistical Society. 1979. p. 100–108.
39.
R Core Team. R: A language and environment for statistical computing. 2014.
40.
Jesus AA, Liphaus BL, Silva CA, Bando SY, Andrade LE, Coutinho A, et al. Complement and antibody primary immunodeficiency in juvenile systemic lupus erythematosus patients. Lupus. 2011;20(12):1275–84.PubMedCrossRef
41.
42.
Lee-Kirsch MA, Gong M, Chowdhury D, Senenko L, Engel K, Lee YA, et al. Mutations in the gene encoding the 3'-5' dna exonuclease TREX1 are associated with systemic lupus erythematosus. Nat Genet. 2007;39(9):1065–7.PubMedCrossRef
43.
Al-Mayouf SM, Sunker A, Abdwani R, Abrawi SA, Almurshedi F, Alhashmi N, et al. Loss-of-function variant in DNASE1L3 causes a familial form of systemic lupus erythematosus. Nat Genet. 2011;43(12):1186–8.PubMedCrossRef
44.
Ramos-Casals M, Campoamor MT, Chamorro A, Salvador G, Segura S, Botero JC, et al. Hypocomplementemia in systemic lupus erythematosus and primary antiphospholipid syndrome: prevalence and clinical significance in 667 patients. Lupus. 2004;13(10):777–83.PubMedCrossRef
45.
Gandino IJ, Scolnik M, Bertiller E, Scaglioni V, Catoggio LJ, Soriano ER. Complement levels and risk of organ involvement in patients with systemic lupus erythematosus. Lupus Sci Med. 2017;4(1):e000209.PubMedPubMedCentralCrossRef
46.
Mathian A, Mouries-Martin S, Dorgham K, et al. Ultrasensitive serum interferon-α quantification during SLE remission identifies patients at risk for relapse. Ann Rheum Dis. 2019;78(12):1669–76.PubMedCrossRef
47.
Catalina MD, Bachali P, Geraci NS, Grammer AC, Lipsky PE. Gene expression analysis delineates the potential roles of multiple interferons in systemic lupus erythematosus. Commun Biol. 2019;2:140 Published 2019 Apr 23.PubMedPubMedCentralCrossRef
48.
Piscianz E, Cuzzoni E, Sharma R, Tesser A, Sapra P, Tommasini A. Reappraisal of antimalarials in interferonopathies: new perspectives for old drugs. Curr Med Chem. 2018;25(24):2797–810.PubMedCrossRef
49.
Sanchez GAM, Reinhardt A, Ramsey S, Wittkowski H, Hashkes PJ, Berkun Y, et al. Jak1/2 inhibition with baricitinib in the treatment of autoinflammatory interferonopathies. J Clin Invest. 2018;128(7):3041–52.PubMedPubMedCentralCrossRef
50.
An J, Minie M, Sasaki T, Woodward JJ, Elkon KB. Antimalarial drugs as immune modulators: new mechanisms for old drugs. Annu Rev Med. 2017;68:317–30.PubMedCrossRef
51.
Schwartz DM, Kanno Y, Villarino A, Ward M, Gadina M, O'Shea JJ. Jak inhibition as a therapeutic strategy for immune and inflammatory diseases. Nat Rev Drug Discov. 2017;16(12):843–62.PubMedCrossRef
52.
Wallace DJ, Furie RA, Tanaka Y, Kalunian KC, Mosca M, Petri MA, et al. Baricitinib for systemic lupus erythematosus: a double-blind, randomised, placebo-controlled, phase 2 trial. Lancet. 2018;392(10143):222–31.PubMedCrossRef
53.
Idborg H, Zandian A, Sandberg AS, Nilsson B, Elvin K, Truedsson L, et al. Two subgroups in systemic lupus erythematosus with features of antiphospholipid or sjögren's syndrome differ in molecular signatures and treatment perspectives. Arthritis Res Ther. 2019;21(1):62.PubMedPubMedCentralCrossRef
Metadata
Title
Higher interferon score and normal complement levels may identify a distinct clinical subset in children with systemic lupus erythematosus
Authors
Alessandra Tesser
Luciana Martins de Carvalho
Paula Sandrin-Garcia
Alessia Pin
Serena Pastore
Andrea Taddio
Luciana Rodrigues Roberti
Rosane Gomes de Paula Queiroz
Virginia Paes Leme Ferriani
Sergio Crovella
Alberto Tommasini
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 1/2020
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/s13075-020-02161-8

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