T Cell Numbers Relate to Bone Involvement in Gaucher Disease

Lacerda, Lúcia; Arosa, Fernando A.; Lacerda, Rosa; Cabeda, José Manuel; Porto, Graça; Amaral, Olga; Fortuna, A; Pinto, Rui; Oliveira, Pedro; McLaren, C. E.; Miranda, Clara Sá; Sousa, Maria de

doi:10.1006/bcmd.1999.0237

Cited by 52 publications

(45 citation statements)

References 29 publications

(22 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…We did not find disturbed absolute CD8+ cell counts, either in patients with or in those without bone involvement. This finding argues with what other studies have reported, namely, that GD patients with bone involvement have reduced absolute CD8 + cell counts (Lacerda et al 1999). This discrepancy might be attributed to the relatively small number of osteopathic patients included in our study (n ¼ 5).…”

Section: Discussionsupporting

confidence: 88%

“…Among few studies, Balreira et al (2005) demonstrated that patients, either under enzyme replacement therapy (ERT) or not, have decreased proportion of CD4+ cells and increased proportion of CD8+ cells. Lacerda et al (1999), however, found that both CD4+ and CD8+ absolute numbers were decreased in patients with bone manifestations. Moreover, Burstein et al (1987) reported decreased number of NKT cells, whereas Braudeau et al (2013) demonstrated that untreated patients exhibit low NK, T gd2 , and naive CD4+ cells and high CD4+ memory T-cell counts.…”

Section: Introductionmentioning

confidence: 86%

See 1 more Smart Citation

Severe Impairment of Regulatory T-Cells and Th1-Lymphocyte Polarization in Patients with Gaucher Disease

et al. 2014

View full text Add to dashboard Cite

We investigated peripheral blood T-lymphocyte subpopulations and intracellular expression of IFN-g, IL-4, IL-10, and IL-13, by whole blood flow cytometry, in 22 type I Gaucher disease (GD) patients. Results were compared with those of 19 sex-and age-matched controls. Patients with GD exhibited decreased frequencies and absolute numbers of CD3+/CD4+ helper T lymphocytes (40.8 AE 9.8% vs. 49.4 AE 5.7%, p ¼ 0.002, and 0.77 AE 0.33 vs. 1.04 AE 0.28 Â 10 9 /mL, p ¼ 0.011), as well as increased frequencies of CD3+CD8+ suppressor T lymphocytes (23.8 AE 8.0% vs. 18.4 AE 3.8%, p ¼ 0.010), resulting in a significantly decreased CD4/CD8 cell ratio (p < 0.001). Moreover, they had significantly increased percentages of IFNg-producing both CD4+ and CD8+ T cells (p ¼ 0.0003 and p ¼ 0.023, respectively), implying a TH-1 polarization pattern. Finally, patients with GD had decreased percentages and absolute numbers of CD4 +CD25 dim T lymphocytes (p ¼ 0.033 and p ¼ 0.007, respectively), of CD4+CD25 high T lymphocytes (p ¼ 0.039 and p ¼ 0.016, respectively), and of CD4+CD25 high FOXP3+ regulatory T cells (p ¼ 0.036 and p ¼ 0.019, respectively). Our results demonstrate that patients with GD have a significant numerical impairment of T-helper lymphocytes and a constitutive TH1 direction pattern of activation of both CD4+ and CD8+ cells, associated with a significant decrease of T-regs. Ineffective T-cell control may explain the chronic inflammatory reaction and the increased incidence of lymphoid malignancies, which have been repeatedly reported among patients with GD.

show abstract

Section: Discussionsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 86%

Severe Impairment of Regulatory T-Cells and Th1-Lymphocyte Polarization in Patients with Gaucher Disease

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Of particular relevance to the process of FL transformation is whether the transformed lymphoma arises directly from FL, or might arise from additional genetic events in a lymphoma progenitor cell. Such a model is supported in findings by Carlotti et al 4 and those of Ruminy et al 5 wherein intraclonal diversity, as defined by the patterns of somatic hypermutation occurring in FL and transformed lymphoma, is more complex than previously described.…”

supporting

confidence: 55%

“…on March 28, 2019. by guest www.bloodjournal.org From bone involvement, but it is uncertain whether this is a primary or secondary phenomenon. 4 Adipocytes are significant players in bone metabolism, but little is known about the interactions between Gaucher cells and fat cells and how they might influence bone mineralization. Altered glucose metabolism, insulin resistance, and abnormal adiponectin levels that may affect bone mineralization have been reported in untreated GD1 patients, but their clinical importance is unclear.…”

Section: O C T O B E R 2 0 0 9 I V O L U M E 1 1 4 N U M B E R 1 mentioning

confidence: 99%

Mesenchymal gaucho homing on the range

Weinreb

2009

Blood

View full text Add to dashboard Cite

show abstract

“…The involvement of immune cells has been implicated, but the underlying molecular defect is poorly understood (6)(7)(8)(9). For example, GD has been associated with impaired host-defense against microbial infections (10,11), up-regulation of T-helper (Th)1 and Th2 cytokines (6,12,13), dysfunction of monocytes (14), and an increased risk for lymphoid malignancies, most strikingly for multiple myeloma (15)(16)(17)(18).…”

mentioning

confidence: 99%

Gaucher disease geneGBAfunctions in immune regulation

Liu

Halene

Yang

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Inherited deficiency of acid β-glucosidase (GCase) due to biallelic mutations in the GBA (glucosidase, β, acid) gene causes the classic manifestations of Gaucher disease (GD) involving the viscera, the skeleton, and the lungs. Clinical observations point to immune defects in GD beyond the accumulation of activated macrophages engorged with lysosomal glucosylceramide. Here, we show a plethora of immune cell aberrations in mice in which the GBA gene is deleted conditionally in hematopoietic stem cells (HSCs). The thymus exhibited the earliest and most striking alterations reminiscent of impaired T-cell maturation, aberrant B-cell recruitment, enhanced antigen presentation, and impaired egress of mature thymocytes. These changes correlated strongly with disease severity. In contrast to the profound defects in the thymus, there were only limited cellular defects in peripheral lymphoid organs, mainly restricted to mice with severe disease. The cellular changes in GCase deficiency were accompanied by elevated T-helper (Th)1 and Th2 cytokines that also tracked with disease severity. Finally, the proliferation of GCase-deficient HSCs was inhibited significantly by both GL1 and Lyso-GL1, suggesting that the “supply” of early thymic progenitors from bone marrow may, in fact, be reduced in GBA deficiency. The results not only point to a fundamental role for GBA in immune regulation but also suggest that GBA mutations in GD may cause widespread immune dysregulation through the accumulation of substrates.

show abstract

T Cell Numbers Relate to Bone Involvement in Gaucher Disease

Cited by 52 publications

References 29 publications

Severe Impairment of Regulatory T-Cells and Th1-Lymphocyte Polarization in Patients with Gaucher Disease

Severe Impairment of Regulatory T-Cells and Th1-Lymphocyte Polarization in Patients with Gaucher Disease

Mesenchymal gaucho homing on the range

Gaucher disease geneGBAfunctions in immune regulation

Contact Info

Product

Resources

About