Extensive Serum Cytokine Analysis in Patients with Macrophage Activation Syndrome Complicating Systemic Juvenile Idiopathic Arthritis

Mao Mizuta¹, Masaki Shimizu¹, Natsumi Inoue¹, Kazuko Kasai², Yasuo Nakagishi³ and Akihiro Yachie⁴, ¹Department of Pediatrics, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan, ²Department of Pediatric Rheumatology, Hyogo Prefectural Kobe Children’s Hospital, kobe, Japan, ³Department of Pediatric Rheumatology, Hyogo Prefectural Kobe Children’s Hospital, Kobe, Japan, ⁴Department of Pediatrics, Graduate School of Medical Sciences, Kanazawa University,, Kanazawa, Japan

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: macrophage activation syndrome and tocilizumab, Systemic JIA

Session Information

Date: Tuesday, November 7, 2017

Title: Pediatric Rheumatology – Pathogenesis and Genetics Poster

Session Type: ACR Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose:

The pathogenesis of Macrophage activation syndrome (MAS) complicating systemic juvenile idiopathic arthritis (s-JIA) is still unknown, but overproduction of proinflammatory cytokines from activated T lymphocytes and macrophages plays an important role to develop MAS. To understand the pathogenesis of MAS and to identify serum biomarker for the diagnosis of MAS, we employed an antibody array that simultaneously detects 174 serum cytokines.

Methods:

Twenty five patients with s-JIA and 4 healthy controls (HCs) were analyzed. Among 25 s-JIA patients, 15 patients including 5 patients receiving tocilizumab (TCZ) were complicated with MAS. Serum cytokine levels were quantified by Raybio Human Cytokine Antibody Array. Serum CXCL9 levels were quantified by enzyme-linked immunosorbent assay. The results were compared with the clinical features of MAS.

Results:

We identified fourteen cytokines whose levels increased in MAS compared to those in active phase of s-JIA. Of which, CXCL9, an interferon-γ induced chemokine, increased most significantly with the development of MAS. The cytokine profile during active phase of s-JIA was quite different between those in s-JIA patients with MAS and without MAS. Eighteen cytokines and 72 cytokines were lower in patients receiving TCZ compared to those in patients not receiving TCZ in active phase of s-JIA and in MAS, respectively. Serum CXCL9 levels were significantly elevated in MAS compared to those in the acute phase of s-JIA. Serum CXCL9 levels profoundly and rapidly increased as MAS developed and correlated positively with disease activity. Serum CXCL9 levels were significantly lower in patients receiving TCZ but those reflected disease activity.

Conclusion:

The elevated levels of CXCL9 and their correlation with disease activity of MAS indicate a pivotal role of IFN-γ in MAS. Monitoring of serum CXCL9 is useful for the evaluation of disease activity in s-JIA and MAS. The expression of many inflammatory cytokines decreased in patients receiving TCZ, suggesting suppress of many cytokines other than IL-6 by TCZ is closely related to masking of clinical symptoms of MAS and s-JIA during TCZ therapy.

Disclosure: M. Mizuta, None; M. Shimizu, None; N. Inoue, None; K. Kasai, None; Y. Nakagishi, None; A. Yachie, None.

To cite this abstract in AMA style:

Mizuta M, Shimizu M, Inoue N, Kasai K, Nakagishi Y, Yachie A. Extensive Serum Cytokine Analysis in Patients with Macrophage Activation Syndrome Complicating Systemic Juvenile Idiopathic Arthritis [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/extensive-serum-cytokine-analysis-in-patients-with-macrophage-activation-syndrome-complicating-systemic-juvenile-idiopathic-arthritis/. Accessed .

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