The levels of serum soluble CD86 are correlated with the expression of CD86 variant 3 gene and are prognostic indicators in patients with myeloma

• Published in: Experimental hematology Vol. 121; pp. 38 - 47.e2
• Main Authors: Kinoshita, Ryosuke, Ishibashi, Mariko, Handa, Hiroshi, Sasaki, Makoto, Imai, Yoichi, Tanaka, Norina, Ito, Shigeki, Sunakawa-Kii, Mika, Kaito, Yuta, Asayama, Toshio, Komatsu, Norio, Tanaka, Junji, Odajima, Takeshi, Sugimori, Hiroki, Yamaguchi, Hiroki, Inokuchi, Koiti, Tamura, Hideto
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.05.2023
• Subjects: B7-2 Antigen - blood; B7-2 Antigen - genetics; Disease Progression; Humans; Multiple Myeloma - diagnosis; Multiple Myeloma - genetics; Prognosis
• ISSN: 0301-472X; 1873-2399
• DOI: 10.1016/j.exphem.2023.01.006

•Soluble forms of CD86 (sCD86) were detected in serum from patients with multiple myeloma.•Patients with high concentrations of sCD86 had aggressive clinical disease.•Patients with high concentrations of sCD86 had a shorter overall survival time.•Transcripts of CD86 variant 3 were detectable in primary myeloma cells.•The levels of serum sCD86 were correlated with the messenger RNA (mRNA) levels of CD86 variant 3. We previously showed that cell-surface CD86 expressed on multiple myeloma (MM) cells contributed to not only tumor growth but also antitumor cytotoxic T-lymphocyte responses mediated by induction of IL-10-producing CD4+ T cells. The soluble form of CD86 (sCD86) was also detected in serum from patients with MM. Thus, to determine whether sCD86 levels are a useful prognostic factor, we investigated the association of serum sCD86 levels with disease progression and prognosis in 103 newly diagnosed patients with MM. Serum sCD86 was detected in 71% of the patients with MM but was only rarely detected in patients with monoclonal gammopathy of undetermined significance and healthy controls, and the level was significantly increased in patients with advanced-stage MM. When we examined differences in clinical characteristics according to the level of serum sCD86, those in the high (≥2.18 ng/mL, n = 38) group exhibited more aggressive clinical characteristics, with shorter overall survival times compared with those in the low (<2.18 ng/mL, n = 65) group. On the other hand, it was difficult to stratify the patients with MM into different risk groups based on the expression levels of cell-surface CD86. The levels of serum sCD86 were significantly correlated with the expression levels of the messenger RNA (mRNA) transcripts of CD86 variant 3, which lack exon 6, resulting in a truncated transmembrane region, and its variant transcripts were upregulated in the high group. Thus, our findings suggest that sCD86 can be easily measured in peripheral blood samples and is a useful prognostic marker in patients with MM.