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Jung, Kim, Son, Kim, Kim, Lee, Park, Lee, and Yoo: Bone Marrow Findings, and TNF-α, IL-18 Expression in Bone Marrow of Adult Onset Still's Disease Patients
Original Article

J Korean Rheum Assoc 2009;16(2):87-94.

Published online: 20 June 2009

DOI: https://doi.org/10.4078/jkra.2009.16.2.87

Bone Marrow Findings, and TNF-α, IL-18 Expression in Bone Marrow of Adult Onset Still's Disease Patients

Kyong Hee Jung1, 4, Hye Yong Kim1, Chang Nam Son1, Joo Hyung Kim1, Won Jun Kim1, Kyeong A Lee1, Ho Hyun Park2, Woong Soo Lee3, Dae Hyun Yoo1, 4

1Department of Internal Medicine, The Hospital for Rheumatic Disease, Hanyang University College of Medicine, Seoul, Korea

2Department of Pathology, The Hospital for Rheumatic Disease, Hanyang University College of Medicine, Seoul, Korea

3Department of Laboratory Medicine, The Hospital for Rheumatic Disease, Hanyang University College of Medicine, Seoul, Korea

4Department of Rheumatology, The Hospital for Rheumatic Disease, Hanyang University College of Medicine, Seoul, Korea

Received 21 August 2009       Revised 24 March 2009       Accepted 25 March 2009

Copyright © 2009 The Korean Rheumatism Association

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Objective

Inflammatory cytokines may play important roles in the pathogenesis of adult onset Still's disease. The enhanced expression of IL-18 was reported in the bone marrow of a Japanese systemic onset juvenile rheumatoid arthritis patient but not in the other organs. To date, there are very few studies relating the bone marrow and AOSD. This study examined the bone marrow findings as well as TNF-α and IL-18 expression in the bone marrow of AOSD patients.

Methods

A retrospective study was performed on 15 AOSD patients who had undergone a bone marrow examination at a university hospital. The clinical and laboratory findings, as well as the bone marrow findings, were analyzed. Immunohistochemistry of IL-18 and TNF-α in bone marrow was performed.

Results

The bone marrow cellularity and myeloid/erythroid cell ratio showed no correlation with the clinical and laboratory findings. TNF-α was expressed at 0.8∼9.8% and IL-18 was expressed at 0.4∼9.8% of bone marrow cells. Cytokine expression was not associated with the clinical patterns of AOSD. The platelet count correlated with the bone marrow TNF-α expression but TNF-α did not correlate with IL-18 expression.

Conclusion

TNF-α and IL-18 expression in bone marrow were observed in some AOSD patients but there was no correlation with the other clinical and laboratory findings except for the platelet count.

Keywords: Adult onset Still's disease, Tumor necrosis factor-alpha, Interleukin-18, Bone marrow

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Fig. 1.
Correlation between bone marrow TNF-α expression and platelet counts (The correlation coefficient was analyzed by Sperman's rank correlation test. n=15, r=0.578, p＜0.005).
jkra-16-87f1.tif
Fig. 2.
Correlation between bone marrow TNF-α and IL-18 expression (r=0.417, p=0.122).
jkra-16-87f2.tif
Table 1.
Clinical characteristics of AOSD patients
  Age Gender Fever Rash Serositis Hepatosplenomegaly Arthralgia/ Arthritis 　　Clinical pattern
A 39 M ＋ － － ＋ ＋ Monocyclic
B 24 F ＋ ＋ － ＋ ＋ Monocyclic
C 26 F ＋ ＋ － － － Monocyclic
D 30 F ＋ － － ＋ ＋ Monocyclic
E 29 F ＋ － － ＋ － Monocyclic
F 38 F ＋ － － － ＋ Monocyclic
G 24 F ＋ ＋ ＋ ＋ ＋ Monocyclic
H 58 F ＋ ＋ － ＋ ＋ Polycyclic
I 19 F ＋ ＋ ＋ ＋ － Polycyclic
J 53 F ＋ － － ＋ ＋ Polycyclic
K 32 M ＋ － － ＋ ＋ Chronic articular
L 50 M ＋ ＋ － ＋ ＋ Chronic articular
M 27 F ＋ ＋ － ＋ ＋ Chronic articular
N 31 F ＋ － － ＋ ＋ Chronic articular
O 33 F ＋ ＋ － － ＋ Chronic articular
Table 2.
Laboratory findings of the AOSD patients
  WBC Hb PLT ESR CRP Ferritin RF ANA M/E Megakaryocyte y Cellularity Storage iron
A 14,300 12.5 213 44 19.5 46,792 – – N adequate 60% NA
B 20,800 12.4 257 76 15.2 ＞2,000 – – N dequate 60% ↓
C 29,100 12.9 518 34 1.8 647 – – N dequate 50% ↓
D 5,200 8.8 163 103 2.4 10,772 – – N adequate 70% NA
E 9,400 12.2 223 61 5.6 22,968 – – ↑ adequate 60% ↑
F 13,300 11.1 216 20 7.3 6,287 – – ↑ adequate 80% adequate
G 17,600 12.5 183 137 18.6 618.5 – – N adequate 60% ↑
H 14,600 11.4 375 59 21.6 ＞2,000 – – ↑ ↓ 40% NA
I 3,000 6.9 99 42 1.5 1,694 – – N ↑ 90% NA
J 12,900 7.8 263 76 4.44 5,137 – – N adequate 70% NA
K 3,600 9.2 144 81 4.26 15,468 – – N adequate 50% adequate
L 11,100 11.3 196 144 15.6 29,229 – – ↑ adequate 70% ↑
M 2,700 10.7 79 46 14 11,272 – – N adequate 50% adequate
N 2,600 9.1 84 31 1.2 10,486 – – N adequate 80% adequate
O 26,600 9.3 346 96 11.2 2,787 – – ↑ adequate 70% adequate

Ferritin (ng/mL), RF (0∼15 IU/mL:－), ANA(＞1：100)

PLT: platelet, RF: rheumatoid factor, M/E: myeloid/erythroid ratio, N: normal, NA: not adequate, ↑: increased, ↓: decreased

Table 3.
TNF-α and IL-18 expression in the bone marrow of AOSD patients
  PATTERN TNF-α (%) IL-18 (%)
A Monocyclic 0.8 0.4
B Monocyclic 2.8 4.2
C Monocyclic 5.8 2.8
D Monocyclic 3.0 1.6
E Monocyclic 6.8 6.4
F Monocyclic 2.0 2.8
G Monocyclic 5.0 9.8
H Polycyclic 9.8 8.2
I Polycyclic 2.8 2.2
J Polycyclic 2.8 3.8
K Chronic articular 1.4 2.2
L Chronic articular 2.8 2.2
M Chronic articular 2.6 0.8
N Chronic articular 2.4 5.4
O Chronic articular 5.4 0.4
Mean±SD 3.7±2.3 3.5±2.8

SD: standard deviation

Table 4.
Mean cytokine expression according to the three clinical patterns of AOSD patients
  Monocyclic Polycyclic Chronic articular
TNF-α 3.7±2.1% 5.1±4.0% 2.9±1.4%
IL-18 4.0±3.1% 4.7±3.1% 2.2±1.9%
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