Reduced Serum B7-H3 Levels in Patients with Ankylosing Spondylitis

Yan, Rui; Hu, Yae; Pan, Yu; Wen, Hongtao; Feng, Ping; Yang, Shun Fa

doi:10.1007/s10753-014-0103-z

Cited by 11 publications

(6 citation statements)

References 17 publications

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“…This suggests that mB7‐H3 may be cleaved to form sB7‐H3, this cleavage may be result in lower expression on the cellular membrane in AITD. Supporting this hypothesis, sB7‐H3 has been found in serum 13 and sB7‐H3 level has been associated with autoimmune diseases such as MS, AS, and RA 14–16 . In this study, however, we did not find any association between plasma sB7‐H3 levels and AITD development (Figure 2).…”

Section: Discussionsupporting

confidence: 42%

“…sB7‐H3 is cleaved from mB7‐H3 13 . Both mB7‐H3 and sB7‐H3 are associated with various autoimmune diseases such as rheumatoid arthritis (RA), multiple sclerosis (MS) and ankylosing spondylitis (AS) 14–16 …”

Section: Introductionmentioning

confidence: 99%

“…13 Both mB7-H3 and sB7-H3 are associated with various autoimmune diseases such as rheumatoid arthritis (RA), multiple sclerosis (MS) and ankylosing spondylitis (AS). [14][15][16] B7-H4, also known as VTCN1, is a co-inhibitory molecule of the B7 family that inhibits T-cell proliferation, cytokine secretion, and cytotoxicity. 7 A putative B7-H4 receptor has not yet been identified, but it was recently reported that B7-H4Ig binds to Sema3a/Nrp-1/ Plexin A4 complex.…”

Section: Introductionmentioning

confidence: 99%

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Association of B7H3 and B7H4 gene polymorphisms and protein expression with the development and prognosis of autoimmune thyroid diseases

Ozaki

Inoue

Iwatani

et al. 2023

Clinical Endocrinology

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Background: The prognosis of autoimmune thyroid diseases (AITDs), including Graves' disease (GD) and Hashimoto's disease (HD), varies among patients. B7-H3 and B7-H4, members of the B7 family of proteins, regulate immune response. To clarify the association of B7-H3 and B7-H4 with the pathogenesis and prognosis of AITDs, we examined the expression of the soluble and membrane form of B7-H3 and B7-H4 and genotyped single nucleotide polymorphisms (SNPs) in the B7H3 and B7H4 genes. Methods:We examined the expression of the membrane form of B7-H3 and B7-H4 by flow cytometry and their soluble forms by enzyme-linked immunosorbent assay. We genotyped SNPs in B7H3 and B7H4 in 187 GD patients, 217 HD patients, and 110 healthy volunteers using the PCR-RFLP method.Results: The frequency of the B7H3 rs3816661 CC genotype was higher in patients with severe HD. G carriers of B7H4 rs10754339 A/G and B7H4 rs13505 T/G were more frequent in patients with AITD. A carrier of B7H4 rs10158166 A/G and C carriers of B7H4 rs3806373 C/T were more frequent in patients with intractable GD. The proportion of B7-H3 + monocytes was higher in the CC genotype of B7H3 rs3816661 C/T than in the other genotypes and was lower in patients with GD and HD than in healthy controls. The concentration of soluble B7-H4 was lower in the TG genotype of B7H4 rs13505 T/G than in the TT genotype and was higher in patients with AITD than in healthy controls. Conclusion:B7H3 and B7H4 are associated with AITD susceptibility and prognosis.

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Section: Discussionsupporting

confidence: 42%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Association of B7H3 and B7H4 gene polymorphisms and protein expression with the development and prognosis of autoimmune thyroid diseases

Ozaki

Inoue

Iwatani

et al. 2023

Clinical Endocrinology

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“…The cellular role of B7-H3 remains controversial until now [10] . Earlier studies, including our previous study, have shown that B7-H3 is associated with autoimmune diseases, such as RA, myasthenia gravis, ankylosing spondylitis, and systemic lupus erythematosus [11][12][13][14] . The expression of B7-H3 on peripheral blood monocytes of RA patients is closely related to clinical manifestations, although the mechanism of action of B7-H3 in RA remains unclear.…”

Section: Introductionmentioning

confidence: 66%

B7-H3 blockade decreases macrophage inflammatory response and alleviates clinical symptoms of arthritis

et al. 2022

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Background: The costimulatory molecule B7-H3 is an immunoregulatory protein that plays an important role in the course of autoimmune diseases. It is also involved in the regulation of in ammatory responses in the body. Studies have shown that B7-H3 is highly expressed in peripheral blood monocytes of rheumatoid arthritis (RA) patients and its expression is closely related to the clinical parameters of the disease. In this study we aimed to determine what the implication of high B7-H3 expression for the disease severity in human RA and mouse model of arthritis is, and whether targeting this molecule could constitute a new therapeutic approach.Methods: We combined histopathological scoring of the joint cavity of collagen-induced arthritis (CIA) mice with immuno uorescent studies of B7-H3 expression on macrophages. We assessed the function of B7-H3 in relation with the pro-in ammatory role of macrophage through small RNA interference. Then we studied the molecular pathways liking B7-H3 with the pro-in ammatory activity of macrophages by multiplex ow cytometry, western blot and quantitative real-time PCR. The therapeutic bene t of anti-B7-H3 blocking was probed in mouse with CIA.Results: Histopathological and histological examination showed a positive correlation between expression of B7-H3 on macrophages and disease activity score, degree of destruction of the joint cavity, and pannus formation. It was also correlated with increased expression of the pro-in ammatory cytokine TNF-α in the joint cavity tissue and TNF-α level in peripheral serum. Knocking down B7-H3 expression through stable expression of small interfering RNA in human and mouse mononuclear phagocytic cell lines weakened the in ammatory response of the cells. Further molecular analyses indicated that the regulation of the in ammatory response through B7-H3 involved NF-κB signaling. Treatment of CIA mice with anti-B7-H3 reduced the clinical manifestation of arthritis and downregulated the expression of proin ammatory cytokines.Conclusions: We con rmed increased expression of B7-H3 in arthritis and established a positive correlation between disease severity and expression of B7-H3 on macrophages. Through functional approaches in vitro and in vivo, we also demonstrated the therapeutic bene ts of targeting B7-H3 for dampening macrophages' in ammatory responses in RA.

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“…Of note, the inhibitory function of B7‐H3 on T‐cell proliferation, activation and cytokine production was also reported in recent studies (Wang et al., 2016; Suh et al., 2003). It was found that serum B7‐H3 levels in AS were significantly lower than healthy individuals, and the reduced serum B7‐H3 levels were negatively correlated with AS Disease Activity Score (ASDAS), implying the potential role of B7‐H3 in AS (Yan et al., 2015).…”

Section: Introductionmentioning

confidence: 99%

Association analysis of B7‐H3 and B7‐H4 gene single nucleotide polymorphisms in susceptibility to ankylosing spondylitis in eastern Chinese Han population

Chen

Yang

et al. 2021

Int J Immunogenetics

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This study was conducted to describe the association between the genetic variation of the recently identified immune checkpoint molecules B7-H3 and B7-H4, and the susceptibility to ankylosing spondylitis (AS). Two single nucleotide polymorphisms (SNPs) of B7-H3 gene and three SNPs of B7-H4 gene were genotyped in 649 AS patients and 646 age-and sex-matched healthy controls. Allele, genotype frequencies and different inheritance models were performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs), and the demographic and clinical parameters of patients were recorded.Our data indicated that B7-H4 rs10801935 and rs3738414 polymorphisms were correlated with AS susceptibility. In the stratification analyses, the minor A allele and GA genotype of B7-H4 rs3738414 increased the risk of AS in male patients (OR = 1.244, 95%CI = 1.026-1.508; OR = 1.453, 95%CI = 1.120-1.886, respectively). However, the association did not reach statistical significance after Bonferroni correction. Furthermore, haplotype analysis revealed that B7-H4 haplotype block TAG was a risk factor for the onset of AS (OR = 1.190, 95%CI = 1.020-1.389). These findings suggested that B7-H4 gene polymorphism may contribute to AS susceptibility in eastern Chinese Han population.

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Reduced Serum B7-H3 Levels in Patients with Ankylosing Spondylitis

Cited by 11 publications

References 17 publications

Association of B7H3 and B7H4 gene polymorphisms and protein expression with the development and prognosis of autoimmune thyroid diseases

Association of B7H3 and B7H4 gene polymorphisms and protein expression with the development and prognosis of autoimmune thyroid diseases

B7-H3 blockade decreases macrophage inflammatory response and alleviates clinical symptoms of arthritis

Association analysis of B7‐H3 and B7‐H4 gene single nucleotide polymorphisms in susceptibility to ankylosing spondylitis in eastern Chinese Han population

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