Clinical significance of serum IL-18 levels for the diagnosis and monitoring of disease activity

Clinical significance of serum IL-18 levels for the diagnosis and monitoring of disease activity

@SJIA_Foundation

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2 weeks ago 284

Other #nextgen2024 #cureSJIA #stillsdisease #sjia

Clinical significance of serum IL-18 levels for the diagnosis and monitoring of disease activity

@SJIA_Foundation2 weeks ago

Clinical significance of serum IL-18 levels
for the diagnosis and monitoring of disease activity …

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Systemic juvenile idiopathic arthritis (s-JIA)
a systemic inflammatory disorder of unknown etiolog…

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Role of cytokines in the pathogenesis of s-JIA
Mellins ED, et al. Nat Rev Rheumatol. 2011;7:416-26…

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Macrophage activation syndrome (MAS)
s-JIA
Viral infections
Drugs
IFN-γ ↑↑
• Continuous fever
…

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The hallmark of MAS is uncontrolled immune response involving continual activation and expansion of…

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Fever
Rash
Cervical lymphadenopathy
Arthritis
Coronary artery dilation
CRP↑ GOT↑ Complication …

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Kinjo N et al J Clin Apher. 2018；33：117-120
CRP
(mg/dl)
Feve
rRas
h
IVI
G
IF
X
mPS
L
T…

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CQ1.　
What is a useful biomarker for the diagnosis of s-JIA？

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Serum cytokine levels in patients with s-JIA
Serum IL-6 and sTNF-RII levels were significantly ele…

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Serum cytokine levels in patients with s-JIA
Mizuta M, et al. Rheumatology. 2021;60:231-238.
Mizu…

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Serum IL-18 level (pg/ml)
median / range Cutoff value AUC
s-JIA 34,750 (3,000-340,000)
KD 360 (6…

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Serum IL-18 levels
as a biomarker for the diagnosis of s-JIA
ILAR criteria PRINTO criteria
ILAR…

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CQ2.
Is serum IL-18 level useful
for the monitoring of disease activity in s-JIA?

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Disease courses of s-JIA
Singh-Grewal D et al. Arthritis Rheum. 2006;54:1595–1601
Disease activit…

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Serum IL-18 levels
as an indicator of disease activity of s-JIA
MAS MAS MAS relapses relapse
Se…

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106
105
104
103
102
Disease activity
polycyclic
(days)
106
105
104
103
102
Systemic sy…

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0
0.
2
0.
4
0.
6
0.
8
1
0 5 1
0
1
5
persistent（n=18）
Monophasic and polycyclic
（n=4…

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CQ3.
Are there different subtypes of s-JIA
based on cytokine expression pattern?

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● MAS
Distinct clinical features of the 2 s-JIA subsets
based on their serum IL-6 and IL-18 leve…

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CQ4.
Are Serum IL-18 levels useful
for the prediction and diagnosis of MAS?

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Interleukin-18
for predicting the development of MAS
Cut off value 47750 pg/ml
Sensitivity 86.7…

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Interleukin-18
for predicting the development of MAS
P<0.0001
P<0.0001
MAS -
MAS +
MAS
phas…

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CQ5.
What is a useful biomarker for the diagnosis of MAS？

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Low middle high
MAS
Active
TCZ(+)
MAS
Active(MAS+)
Active(MAS-)
TCZ(-)
Extensive cytokine e…

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Biomarkers Cut off values Area under the ROC curve values
Neopterin 19.5 0.9465
CXCL9 3130 0.9333…

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Schulert GS et al. Arthritis Care Res 2018; 70: 409-419より引用一部改変
Biologics modify clinical and labo…

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Shimizu M et al. Cytokine 2012; 58: 287-294
The diagnostic significance of IL-18
as a biomarker…

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Is this episode MAS?
Patient 1: 8 years old boy with s-JIA receiving canakinumab and in remission …

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Is this episode MAS?
Patient 2: 5 years old girl with s-JIA receiving tocilizumab and in remission…

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Is this episode MAS?
Patient 1 Patient 2
IL6
IL-1
8
103
3x103
3x104
105
50
30
10
100
…

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CQ5.
What is the role of IL-18 in the pathogenesis of MAS?

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Day1 Day8 Day10
Pump insert 　　 CpG injection
C57BL/6
Normal Sarine
IL-1β
IL-18
IL-1β+IL-18
M…

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*** ***
IL-18+IL-1β+CpG
IL-1β+CpG
Body weight was significantly decreased in the IL-1β and the c…

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Laboratory findings after CpG injection
WBC (x 10
2/μL)
RBC (x 10
4/μL)
*
ferritin (ng/mL)
N…

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IL-18+IL-1β
IL-18
IL-1β
NS
Untreated
IFN-γ/GAPDH
*
***
*
**
*** ***
IL-18+IL-1β
IL-18
…

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*
***
**
**
*
TNFα/GAPDH
* ***
IFN-γ/GAPDH
TNF-α/GAPDH
Cytokine mRNA levels were regulated…

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Distinct roles of IL-18 and IL-1β
in murine model of MAS
Mizuta M, et al. J Allergy Clin Immunol…

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Conclusions
• Serum IL-18 level is a useful biomarker for the diagnosis and monitoring of disease …

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Thank you for your attentions.
Pediatric Rheumatology and Nephrology Team
in Kanazawa University …

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@SJIA_Foundation

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Comments 1 Info

- @jonathan
- 2w
Awesome

Clinical significance of serum IL-18 levels for the diagnosis and monitoring of disease activity

@SJIA_Foundation

Presentation from Dr. Masaki Shimizu for NextGen 2024. Dr. Shimizu was the Keynote Speaker and talked about his IL-18 lab work.

Other

#nextgen2024 #cureSJIA #stillsdisease #sjia

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