Serum Soluble Interleukin-2 Receptor Is a Biomarker for Pneumocystis jirovecii Pneumonia among Patients with Rheumatoid Arthritis under Methotrexate Therapy

Serum Soluble Interleukin-2 Receptor Is a Biomarker for Pneumocystis jirovecii Pneumonia among Patients with Rheumatoid Arthritis under Methotrexate Therapy

NORIHO SAKAMOTO,¹ SHINTARO HARA,^1,2 HIROSHI ISHIMOTO,¹ SHOTA NAKASHIMA,¹ HIROKAZU YURA,¹ TAKUTO MIYAMURA,¹ DAISUKE OKUNO,¹ ATSUKO HARA,¹ TOMOYUKI KAKUGAWA,¹ HIROYUKI YAMAGUCHI,¹ YASUSHI OBASE,¹ HISAKO KUSHIMA,³ HIROSHI ISHII,³ SHINGO NOGUCHI,⁴ TAKASHI KIDO,⁴ TSUTOMU KOBAYASHI,⁵ YOSHIFUMI SOEJIMA,⁵ SUMAKO YOSHIOKA,⁶ YUJI ISHIMATSU,⁷ KAZUHIRO YATERA,⁴ JUN-ICHI KADOTA8 AND HIROSHI MUKAE¹

¹Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Nagasaki, Japan
²Department of Respiratory Medicine, Aino Memorial Hospital, Unzen, Nagasaki, Japan
³Department of Respiratory Medicine, Fukuoka University Hospital, Fukuoka, Fukuoka, Japan
⁴Department of Respiratory Medicine, School of Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu, Fukuoka, Japan
⁵Department of Respiratory Medicine, Sasebo Chuo Hospital, Sasebo, Nagasaki, Japan
⁶Department of Respiratory Medicine, Nagasaki Harbor Medical Center, Nagasaki, Nagasaki, Japan
⁷Department of Nursing, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Nagasaki, Japan
⁸Department of Respiratory Medicine and Infectious Diseases, Oita University Faculty of Medicine, Yufu, Oita, Japan

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by systemic joint inflammation and may manifest as interstitial pneumonia (IP). Methotrexate (MTX) is one of the main therapeutic drugs used for RA, but MTX could cause severe side effects, including Pneumocystis jirovecii pneumonia (PCP) and IP. Owing to similar symptoms, it is sometimes difficult to discriminate MTX therapy-associated PCP (MTX-PCP) and MTX therapy-associated IP (MTX-IP). Soluble interleukin-2 receptor (sIL-2R) is considered a marker of T-cell activation, and serum sIL-2R levels are elevated in RA and PCP. This led us to hypothesize that serum sIL-2R is a potential biomarker for discriminating MTX-PCP and MTX-IP. Accordingly, we carried out a retrospective analysis of 20 MITX-PCP cases, 30 MTX-IP cases, and as controls, 16 patients with RA-associated IP (RA-IP) and 13 patients with PCP without MTX treatment (PCP group). C-reactive protein and alveolar-arterial oxygen differences were higher in the MTX-PCP group than those in the RA-IP and MTX-IP groups. Importantly, serum levels of sIL-2R in MTX-PCP were significantly higher than those in other three groups. Based on the receiver operating characteristic curve, the cut-off level of sIL-2R resulting in the highest diagnostic accuracy for MTX-PCP was 1,311.5 U/mL, discriminating between MTX-PCP and other groups with 91.7% sensitivity and 78.6% specificity. Thus, patients with MTX-PCP show a higher degree of systemic inflammation, severe hypoxemia, and increased sIL-2R levels compared with those in MTX-IP cases. In conclusion, serum sIL-2R could be a biomarker for PCP diagnosis among patients with RA under MTX therapy.

keywords —— drug-induced pneumonia; interleukin-2 receptor; methotrexate; Pneumocystis jirovecii pneumonia; rheumatoid arthritis

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Tohoku J. Exp. Med., 2019, 248, 209-216

Correspondence: Noriho Sakamoto, M.D., Ph.D., Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, Nagasaki 852-8501, Japan.

e-mail: nsakamot@nagasaki-u.ac.jp