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Pediatric Rheumatology
Published in: Pediatric Rheumatology 1/2021

Open Access 01-12-2021 | Kawasaki Disease | Research article

The “Intermediate” CD14 + CD16 + monocyte subpopulation plays a role in IVIG responsiveness of children with Kawasaki disease

Authors: Yi Seul Kim, Hyun Jin Yang, Seung-Jung Kee, Insu Choi, Kisoo Ha, Katrina K Ki, In Seok Jeong, Hwa Jin Cho

Published in: Pediatric Rheumatology | Issue 1/2021

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Abstract

Background

Kawasaki disease (KD) is an acute, self-limited febrile illness of unknown cause. Intravenous immunoglobulin (IVIG)-resistance are related to greater risk for permanent cardiac complications. We aimed to determine the correlation between monocytes and the phenotype of KD in relation to IVIG responsiveness in children.

Materials and methods

The study cohort included 62 patients who were diagnosed with KD, 20 non febrile healthy controls (NFC), and 15 other febrile controls (OFC). In all enrolled patients, blood was taken at least 4 times and laboratory tests were performed. In addition, subtypes of monocytes were characterized via flow cytometry.

Results

The numbers of intermediate monocytes were significantly lower in IVIG-resistant group compared to IVIG-responsive group before IVIG infusion (p < 0.0001). After infusion, intermediate monocytes decreased in the responsive group, while a trend of increase was observed in the resistant group. Only intermediate monocytes were significant in logistic regression with adjusted OR of 0.001 and p value of 0.03.

Conclusions

CD14 + CD16 + intermediate monocyte may play an important role in IVIG responsiveness among KD children. Low starting levels of intermediate monocytes, followed by a dramatic increase post-IVIG infusion during acute phase of KD are associated with IVIG-resistance. Functional studies on intermediate monocyte may help to reveal the pathophysiology.
Literature
1.
Kawasaki T, Kosaki F, Okawa S, Shigematsu I, Yanagawa H. A new infantile acute febrile mucocutaneous lymph node syndrome (MLNS) prevailing in Japan. Pediatrics. 1974;54(3):271–6.PubMedCrossRef
2.
Tremoulet AH, Best BM, Song S, Wang S, Corinaldesi E, Eichenfield JR, et al. Resistance to intravenous immunoglobulin in children with Kawasaki disease. J Pediatr. 2008;153(1):117–21.PubMedPubMedCentralCrossRef
3.
McCrindle BW, Rowley AH, Newburger JW, Burns JC, Bolger AF, Gewitz M, et al. Diagnosis, treatment, and long-term management of Kawasaki Disease: a scientific statement for health professionals from the American Heart Association. Circulation. 2017;135(17):e927-e99.
4.
5.
6.
Wang GB, Li CR, Zu Y, Yuan XW. [The role of activation of toll-like receptors in immunological pathogenesis of Kawasaki disease]. Zhonghua Er Ke Za Zhi. 2006;44(5):333–6.PubMed
7.
Koga M, Ishihara T, Takahashi M, Umezawa Y, Furukawa S. Activation of peripheral blood monocytes and macrophages in Kawasaki disease: ultrastructural and immunocytochemical investigation. Pathol Int. 1998;48(7):512–7.PubMedCrossRef
8.
Katayama K, Matsubara T, Fujiwara M, Koga M, Furukawa S. CD14 + CD16 + monocyte subpopulation in Kawasaki disease. Clin Exp Immunol. 2000;121(3):566–70.PubMedPubMedCentralCrossRef
9.
Furukawa S, Matsubara T, Jujoh K, Yone K, Sugawara T, Sasai K, et al. Peripheral blood monocyte/macrophages and serum tumor necrosis factor in Kawasaki disease. Clin Immunol Immunopathol. 1988;48(2):247–51.PubMedCrossRef
10.
Swirski FK, Nahrendorf M, Etzrodt M, Wildgruber M, Cortez-Retamozo V, Panizzi P, et al. Identification of splenic reservoir monocytes and their deployment to inflammatory sites. Science (New York, NY). 2009;325(5940):pp. 612–6.CrossRef
11.
12.
Ziegler-Heitbrock L, Ancuta P, Crowe S, Dalod M, Grau V, Hart DN, et al. Nomenclature of monocytes and dendritic cells in blood. Blood. 2010;116(16):e74–80.PubMedCrossRef
13.
Boyette LB, Macedo C, Hadi K, Elinoff BD, Walters JT, Ramaswami B, et al. Phenotype, function, and differentiation potential of human monocyte subsets. PloS one. 2017;12(4):e0176460.PubMedPubMedCentralCrossRef
14.
Wong KL, Tai JJ, Wong WC, Han H, Sem X, Yeap WH, et al. Gene expression profiling reveals the defining features of the classical, intermediate, and nonclassical human monocyte subsets. Blood. 2011;118(5):e16–31.PubMedCrossRef
15.
Wong KL, Yeap WH, Tai JJ, Ong SM, Dang TM, Wong SC. The three human monocyte subsets: implications for health and disease. Immunol Res. 2012;53(1–3):41–57.PubMedCrossRef
16.
Grip O, Bredberg A, Lindgren S, Henriksson G. Increased subpopulations of CD16(+) and CD56(+) blood monocytes in patients with active Crohn’s disease. Inflamm Bowel Dis. 2007;13(5):566–72.PubMedCrossRef
17.
Rogacev KS, Seiler S, Zawada AM, Reichart B, Herath E, Roth D, et al. CD14 + + CD16 + monocytes and cardiovascular outcome in patients with chronic kidney disease. Eur Heart J. 2011;32(1):84–92.PubMedCrossRef
18.
Rossol M, Kraus S, Pierer M, Baerwald C, Wagner U. The CD14(bright) CD16 + monocyte subset is expanded in rheumatoid arthritis and promotes expansion of the Th17 cell population. Arthritis Rheum. 2012;64(3):671–7.PubMedCrossRef
19.
Gren ST, Grip O. Role of Monocytes and Intestinal Macrophages in Crohn’s Disease and Ulcerative Colitis. Inflamm Bowel Dis. 2016;22(8):1992–8.PubMedCrossRef
20.
Terai M, Kohno Y, Namba M, Umemiya T, Niwa K, Nakajima H, et al. Class II major histocompatibility antigen expression on coronary arterial endothelium in a patient with Kawasaki disease. Hum Pathol. 1990;21(2):231–4.PubMedCrossRef
21.
Sugawara T, Hattori S, Hirose S, Furukawa S, Yabuta K, Shirai T. Immunopathology of the skin lesion of Kawasaki disease. Prog Clin Biol Res. 1987;250:185–92.PubMed
22.
23.
Furukawa S, Matsubara T, Yone K, Hirano Y, Okumura K, Yabuta K. Kawasaki disease differs from anaphylactoid purpura and measles with regard to tumour necrosis factor-alpha and interleukin 6 in serum. Eur J Pediatr. 1992;151(1):44–7.PubMedCrossRef
24.
Maury CP, Salo E, Pelkonen P. Elevated circulating tumor necrosis factor-alpha in patients with Kawasaki disease. J Lab Clin Med. 1989;113(5):651–4.PubMed
25.
Leung DY, Cotran RS, Kurt-Jones E, Burns JC, Newburger JW, Pober JS. Endothelial cell activation and high interleukin-1 secretion in the pathogenesis of acute Kawasaki disease. Lancet. 1989;2(8675):1298–302.PubMedCrossRef
26.
Galeotti C, Kaveri SV, Bayry J. IVIG-mediated effector functions in autoimmune and inflammatory diseases. Int Immunol. 2017;29(11):491–8.PubMedCrossRef
27.
Séïté JF, Hillion S, Harbonnier T, Pers JO. Review: intravenous immunoglobulin and B cells: when the product regulates the producer. Arthritis Rheumatol (Hoboken, NJ). 2015;67(3):595–603.CrossRef
28.
Das M, Karnam A, Stephen-Victor E, Gilardin L, Bhatt B, Kumar Sharma V, et al. Intravenous immunoglobulin mediates anti-inflammatory effects in peripheral blood mononuclear cells by inducing autophagy. Cell Death Dis. 2020;11(1):50.PubMedPubMedCentralCrossRef
29.
30.
Pua HH, Dzhagalov I, Chuck M, Mizushima N, He YW. A critical role for the autophagy gene Atg5 in T cell survival and proliferation. J Exp Med. 2007;204(1):25–31.PubMedPubMedCentralCrossRef
31.
Rockel JS, Kapoor M. Autophagy: controlling cell fate in rheumatic diseases. Nat Rev Rheumatol. 2016;12(9):517–31.PubMedCrossRef
32.
Rioux JD, Xavier RJ, Taylor KD, Silverberg MS, Goyette P, Huett A, et al. Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis. Nat Genet. 2007;39(5):596–604.PubMedPubMedCentralCrossRef
33.
Lin NY, Beyer C, Giessl A, Kireva T, Scholtysek C, Uderhardt S, et al. Autophagy regulates TNFα-mediated joint destruction in experimental arthritis. Ann Rheum Dis. 2013;72(5):761–8.PubMedCrossRef
34.
Yin H, Wu H, Chen Y, Zhang J, Zheng M, Chen G, et al. The Therapeutic and Pathogenic Role of Autophagy in Autoimmune Diseases. Front Immunol. 2018;9:1512.PubMedPubMedCentralCrossRef
35.
Bonam SR, Wang F, Muller S. Autophagy. A new concept in autoimmunity regulation and a novel therapeutic option. J Autoimmun. 2018;94:16–32.PubMedCrossRef
36.
Abe J, Jibiki T, Noma S, Nakajima T, Saito H, Terai M. Gene expression profiling of the effect of high-dose intravenous Ig in patients with Kawasaki disease. J Immunol. 2005;174(9):5837–45.PubMedCrossRef
37.
Kobayashi T, Inoue Y, Takeuchi K, Okada Y, Tamura K, Tomomasa T, et al. Prediction of intravenous immunoglobulin unresponsiveness in patients with Kawasaki disease. Circulation. 2006;113(22):2606–12.PubMedCrossRef
38.
Egami K, Muta H, Ishii M, Suda K, Sugahara Y, Iemura M, et al. Prediction of resistance to intravenous immunoglobulin treatment in patients with Kawasaki disease. J Pediatr. 2006;149(2):237–40.PubMedCrossRef
39.
Sano T, Kurotobi S, Matsuzaki K, Yamamoto T, Maki I, Miki K, et al. Prediction of non-responsiveness to standard high-dose gamma-globulin therapy in patients with acute Kawasaki disease before starting initial treatment. Eur J Pediatr. 2007;166(2):131–7.PubMedCrossRef
40.
Burns JC, Capparelli EV, Brown JA, Newburger JW, Glode MP. Intravenous gamma-globulin treatment and retreatment in Kawasaki disease. US/Canadian Kawasaki Syndrome Study Group. Pediatr Infect Dis J. 1998;17(12):1144–8.PubMedCrossRef
41.
Son MB, Gauvreau K, Ma L, Baker AL, Sundel RP, Fulton DR, et al. Treatment of Kawasaki disease: analysis of 27 US pediatric hospitals from 2001 to 2006. Pediatrics. 2009;124(1):1–8.PubMedCrossRef
42.
Sleeper LA, Minich LL, McCrindle BM, Li JS, Mason W, Colan SD, et al. Evaluation of Kawasaki disease risk-scoring systems for intravenous immunoglobulin resistance. J Pediatr. 2011;158(5):831–5.e3.PubMedCrossRef
43.
Furukawa S, Matsubara T, Jujoh K, Sasai K, Nakachi S, Sugawara T, et al. Reduction of peripheral blood macrophages/monocytes in Kawasaki disease by intravenous gammaglobulin. Eur J Pediatr. 1990;150(1):43–7.PubMedCrossRef
44.
Ichiyama T, Yoshitomi T, Nishikawa M, Fujiwara M, Matsubara T, Hayashi T, et al. NF-kappaB activation in peripheral blood monocytes/macrophages and T cells during acute Kawasaki disease. Clin Immunol (Orlando Fla). 2001;99(3):373–7.CrossRef
Metadata
Title
The “Intermediate” CD14 + CD16 + monocyte subpopulation plays a role in IVIG responsiveness of children with Kawasaki disease
Authors
Yi Seul Kim
Hyun Jin Yang
Seung-Jung Kee
Insu Choi
Kisoo Ha
Katrina K Ki
In Seok Jeong
Hwa Jin Cho
Publication date
01-12-2021
Publisher
BioMed Central
Published in
Pediatric Rheumatology / Issue 1/2021
Electronic ISSN: 1546-0096
DOI
https://doi.org/10.1186/s12969-021-00573-7

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