A Functional Polymorphism in B and T Lymphocyte Attenuator Is Associated with Susceptibility to Rheumatoid Arthritis

Oki, Mie; Watanabe, Norihiko; Owada, Takayoshi; Oya, Yoshihiro; Ikeda, Kei; Saitō, Yasushi; Matsumura, Ryutaro; Seto, Yohei; Iwamoto, Itsuo; Nakajima, Hiroshi

doi:10.1155/2011/305656

Cited by 37 publications

(43 citation statements)

References 48 publications

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“…Like for other immune checkpoint markers PD-1 and CTLA-4, there is a polymorphism of the btla gene that results in less inhibition, and that is associated with rheumatoid arthritis [25]. Several autoimmune diseases, including those with obvious B cell driven pathogenesis, display unequal incidence between sexes, and it possible that this involves differences related to the inhibitory receptors.…”

Section: Discussionmentioning

confidence: 99%

A combination of the activation marker CD86 and the immune checkpoint marker B and T lymphocyte attenuator (BTLA) indicates a putative permissive activation state of B cell subtypes in healthy blood donors independent of age and sex

et al. 2020

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Background: The use of anti-B cell based therapies in immune-mediated diseases targeting general B cell markers or molecules important for B cell function has increased the clinical needs of monitoring B cell subpopulations. Results: We analyzed the expression profile of cell surface markers CD86 and B and T lymphocyte attenuator (BTLA) in B cell subtypes using flow cytometry, including naïve, transitional, switched memory, non-switched memory and double-negative memory B cells and plasmablasts, and investigated the dependence of age and sex in a healthy adult blood donor population. The switched memory B cell subtype displayed a divergent expression of the markers, with increased CD86 and decreased BTLA as compared to non-switched and double negative memory cells, as well as compared to naïve B cells. Plasmablasts expressed highly increased CD86 compared to all other subtypes and a decreased expression of BTLA compared to naïve cells, but still higher compared to the memory cell populations. Transitional B cells had CD86 and BTLA expression similar to the other naïve cells. Conclusions: We show divergent expression of CD86 and BTLA in memory cells and plasmablasts compared to naïve B cells independent of age and sex. Furthermore, a similarly divergent difference of expression pattern was seen between the memory cell subtypes, altogether indicating that the combination of CD86 and BTLA might be markers for a permissive activation state. We suggest the combination of CD86 and BTLA expression on B cell subtypes as a potentially important tool in monitoring the status of B cell subtypes before and after treatments influencing the B cell compartment.

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Section: Discussionmentioning

confidence: 99%

A combination of the activation marker CD86 and the immune checkpoint marker B and T lymphocyte attenuator (BTLA) indicates a putative permissive activation state of B cell subtypes in healthy blood donors independent of age and sex

et al. 2020

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“…Scale bar=20 μm. [21]. Despite this information, the expression and distribution of BTLA in synovium have not been reported.…”

Section: Discussionmentioning

confidence: 99%

The Expression and Anatomical Distribution of BTLA and Its Ligand HVEM in Rheumatoid Synovium

et al. 2011

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Co-inhibitory signaling from B and T lymphocyte attenuator (BTLA) can suppress lymphocyte activation and maintain peripheral tolerance. However, the expression and anatomical distribution of BTLA and its ligand, herpesvirus entry mediator (HVEM), in rheumatoid arthritis (RA) synovium have not been reported. In this study, we analyzed the expression of HVEM and BTLA in RA synovium by immunohistochemistry, and our results showed that both factors were observed in all four cases of RA samples. At the cellular level, both HVEM and BTLA were found on the cell membrane and in the cytoplasm. Fluorescence dual staining demonstrated that HVEM was chiefly on CD3(+) T cells, CD68(+) macrophages, and to a lesser extent was found on CD31(+) endothelial cells. Similarly, the expression of BTLA was observed on infiltrated CD3(+) T cells and CD68(+) macrophages. The co-expression of HVEM and BTLA with some members of the B7 family in these sections was also analyzed, and the results showed that HVEM antigen was also found on B7-H3(+) capillaries, while it was absent on B7-H1(+), B7-DC(+), B7-H4(+), and Z39Ig(+) cells. Interestingly, BTLA was observed on B7-H1(+), B7-H4(+), and HVEM(+) cells in the synovium. The characteristic expression and distribution of BTLA/HVEM in the synovium indicated that their signaling probably affects the pathogenesis of RA, and a clear understanding of their functional roles may further elucidate the pathogenesis of this disease.

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“…In the intracellular region, there are two immunoreceptor tyrosine-based inhibitory motifs (ITIMs). Tyrosine phosphorylation of ITIM motifs induces the recruitment of the phosphatases SHP-1 and SHP-2, which leads to inhibitory effects [28, 30]. We selected two functional SNPs located in exons 4 and 5.…”

Section: Discussionmentioning

confidence: 99%

The Influence of B and T Lymphocyte Attenuator Genetic Variants on Susceptibility to Chronic Hepatitis B Virus Infection

Tang

Fei

et al. 2018

Cell Physiol Biochem

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Background/Aims: B and T lymphocyte attenuator (BTLA) is an immune inhibitory receptor involved in the pathogenesis of chronic viral infections. Little is known about the effects of BTLA gene polymorphisms on chronic hepatitis B virus (HBV) infections. In this study, we investigated whether the polymorphisms of BTLA are associated with the progression of chronic HBV infection. Methods: A total of 382 chronic HBV carriers and 170 healthy individuals in the same region were recruited for this study. The chronic HBV carriers were divided into three groups: asymptomatic HBV carriers (ASC), moderate chronic hepatitis B group (MCHB), and severe chronic hepatitis B group (SCHB). Two BTLA functional single nucleotide polymorphisms (SNPs; rs76844316 and rs9288952) were genotyped by polymerase chain reaction and sequenced directly. Results: The results showed that the frequency of the G allele of rs76844316 was significantly lower in the SCHB group than in the other three groups. Subjects bearing at least one G allele (TG or GG genotype) at rs76844316 had decreased susceptibility to severe chronic hepatitis B compared with those bearing the TT genotype. Haplotype analysis of the two SNPs revealed that the frequency of the G-G haplotype was significantly lower in SCHB patients than in controls. Moreover, in the SCHB group, patients carrying the G allele of rs76844316 tended to have lower ALT levels than those without it. Conclusion: Our findings suggest that the genetic variants of rs76844316 in BTLA influence the susceptibility to severe chronic hepatitis B and might play a protective role against the progression of chronic hepatitis B.

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A Functional Polymorphism in B and T Lymphocyte Attenuator Is Associated with Susceptibility to Rheumatoid Arthritis

Cited by 37 publications

References 48 publications

A combination of the activation marker CD86 and the immune checkpoint marker B and T lymphocyte attenuator (BTLA) indicates a putative permissive activation state of B cell subtypes in healthy blood donors independent of age and sex

A combination of the activation marker CD86 and the immune checkpoint marker B and T lymphocyte attenuator (BTLA) indicates a putative permissive activation state of B cell subtypes in healthy blood donors independent of age and sex

The Expression and Anatomical Distribution of BTLA and Its Ligand HVEM in Rheumatoid Synovium

The Influence of B and T Lymphocyte Attenuator Genetic Variants on Susceptibility to Chronic Hepatitis B Virus Infection

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