Utility of Macrophage-activated Marker CD163 for Diagnosis and Prognosis in Pulmonary Tuberculosis.
BACKGROUND
Among infectious diseases, tuberculosis (TB) is a leading cause of death worldwide. Accumulated knowledge has revealed that macrophages are deeply involved in the progression and pathogenesis of TB. We hypothesized that the evaluation of a macrophage activation marker may be useful in the diagnosis and assessment of pulmonary TB.


OBJECTIVE
To examine the utility of the macrophage activation marker soluble CD163 (sCD163) as a diagnostic tool and measure of disease severity for pulmonary TB and tuberculous pleurisy.


METHODS
We compared the concentration of sCD163 in serum samples of 180 patients with active pulmonary TB with concentrations in serum samples of 45 age- and sex-matched control subjects. We also measured sCD163 in pleural fluid samples of 100 patients with pleural disease, including 31 patients with tuberculous pleurisy.


RESULTS
We found increased serum concentrations of sCD163 in patients with active pulmonary TB compared with those of control subjects (1,643 ± 1,737 ng/ml vs. 533.9 ± 49.3 ng/ml; P < 0.0001). sCD163 levels were also higher in pleural fluid samples of patients with pulmonary TB than in those of patients with non-TB pleurisy (5,239 ± 2,436 ng/ml vs. 2,877 ± 1,191 ng/ml; P < 0.0001). The levels of sCD163 in pleural effusions were significantly higher than serum levels obtained simultaneously from the same patients, particularly for patients with tuberculous pleurisy. Patients with a serum level of sCD163 above 1,300 ng/ml, had a mortality rate that was five times higher than that of patients with a lower sCD163 level (44.6% vs. 6.6%; P < 0.0001 by log-rank test). Microscopic examination of lung and pleural tissue samples showed concordance of enhanced CD163 expression with the presence of caseating granulomas in tissue obtained from patients with TB.


CONCLUSIONS
The macrophage activation marker CD163 was increased in patients with active pulmonary TB compared with age- and sex-matched control subjects. Increased levels of sCD163 were associated with increased mortality in patients with pulmonary TB. sCD163 also showed promise as a diagnostic tool for tuberculous pleurisy. These results warrant further study of sCD163 as a potentially useful biomarker for the diagnosis and assessment of pulmonary TB. Clinical trial registered with www.umin.ac.jp/ctr/index-j.htm (UMIN000003400).
1 Second Division, Department of Internal Medicine, and.
Yuzo
Y
Suzuki
2 Respiratory Medicine, Tenryu Hospital, National Hospital Organization, Hamamatsu, Japan; and.
Masahiro
M
Shirai
3 Respiratory Medicine, Shizuoka General Hospital, Shizuoka, Japan.
Kazuhiro
K
Asada
2 Respiratory Medicine, Tenryu Hospital, National Hospital Organization, Hamamatsu, Japan; and.
Seiichi
S
Miwa
1 Second Division, Department of Internal Medicine, and.
Masato
M
Karayama
1 Second Division, Department of Internal Medicine, and.
Yutaro
Y
Nakamura
1 Second Division, Department of Internal Medicine, and.
Naoki
N
Inui
3 Respiratory Medicine, Shizuoka General Hospital, Shizuoka, Japan.
Toshihiro
T
Shirai
2 Respiratory Medicine, Tenryu Hospital, National Hospital Organization, Hamamatsu, Japan; and.
Hiroshi
H
Hayakawa
4 Department of Diagnostic Pathology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Satoshi
S
Baba
1 Second Division, Department of Internal Medicine, and.
Takafumi
T
Suda
D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000097:blood*; D015214:Antigens, Differentiation, Myelomonocytic / Q000097:blood*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D011956:Receptors, Cell Surface / Q000097:blood*; D014396:Tuberculosis, Pleural / Q000097:blood* / Q000401:mortality; D014397:Tuberculosis, Pulmonary / Q000097:blood* / Q000401:mortality; D000098902:CD163 Antigen
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D011956:Receptors, Cell Surface
CD163; tuberculosis; tuberculous pleurisy