KIR genes and HLA class I ligands in Gaucher disease

Vairo, Filippo Pinto e; Portela, Pâmela; Salim, Patrícia Hartstein; Jobim, Mariana; Netto, Cristina; Dorneles, Alicia; Mittlestadt, Suzana; Jobim, Luiz Fernando Job; Schwartz, Ida Vanessa Döederlein

doi:10.1016/j.gene.2012.12.014

Cited by 5 publications

(5 citation statements)

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“…Although the mechanisms by which GBA1 gene mutations influence GD phenotype remain largely unknown, the main pathogenesis of this disorder is believed to be the lysosomal accumulation of glucocerebroside in mononuclear phagocytes. This process triggers the expression of cytokines and other inflammatory molecules which, in turn, engage other immune cells and ultimately lead to a systemic immune response ( Barak et al , 1999 ; Cox, 2001 ; Boven et al , 2004 ; Liu et al , 2012 ; Pandey and Grabowski, 2013 ; Vairo et al , 2013 ; Thomas et al , 2014 ). Several circulating molecules thought to be secreted by these lipidladen macrophages have been studied as biological markers of disease burden and/or response to enzyme replacement therapy (ERT) ( Aerts et al, 2005 ; Cox, 2006 ).…”

Section: Introductionmentioning

confidence: 99%

The prognostic value of the serum ferritin in a southern Brazilian cohort of patients with Gaucher disease

et al. 2016

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The clinical utility of serum ferritin as a biomarker of disease severity and prognosis in Gaucher disease (GD) is still debated. Here, we aimed to evaluate ferritin and its relation to clinicolaboratory parameters of GD patients seen at the Reference Center for Gaucher Disease of Rio Grande do Sul, Brazil, so as to gather evidence on the utility of ferritin as a biomarker of this condition. A retrospective chart review was performed collecting pre-and posttreatment data from GD patients. Eighteen patients with ferritin levels available before and after treatment were included in the study. Nine of these participants were males, and seventeen had type I GD. All patients were given either enzyme replacement (n = 16) or substrate reduction therapy (n = 2), and ferritin was found to decrease from 756 [318-1441] ng/mL at baseline to 521 [227-626] ng/mL (p=0.025) after 28.8 month soft treatment. Serum ferritin levels did not correlate with measures of disease severity, but showed an association with age at onset of treatment (ρ= 0.880; n = 18; p < 0.001). In conclusion, although serum ferritin did not correlate with disease severity, after a median 28.8 months of treatment, clinical outcomes had clearly improved, and ferritin levels had decreased.

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Section: Introductionmentioning

confidence: 99%

The prognostic value of the serum ferritin in a southern Brazilian cohort of patients with Gaucher disease

et al. 2016

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“…In addition to allelic variation, KIR diversity is characterized by the presence/absence of genes, resulting in the expansion and contraction of KIR haplotypes. The presence or absence of certain KIR genes, as well as of some KIR-HLA receptor-ligand combinations, have been shown to be associated with disease prognosis [8,11,12].…”

Section: Introductionmentioning

confidence: 99%

Association between KIR genotypes and HLA-B alleles on viral load in Southern Brazilian individuals infected by HIV-1 subtypes B and C

et al. 2016

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“…Much is being studied about secondary modifier genes in Mendelian disorders, including GD [[13], [14], [15]]; however, still little is known about how strong is the genotype-phenotype association in GD. In the presented case, both patients harboured the same variants in GBA1 , and although quite similar overall, there were some differences between the two sisters' phenotypes: while patient 2's bone phenotype may be considered somewhat more severe, patient 1's chitotriosidase – a biomarker for GD activity – was more than three times higher at admission than patient 2's.…”

Section: Phenotypementioning

confidence: 99%

Rare GBA1 genotype associated with severe bone disease in Gaucher disease type 1

Paskulin

Starosta

Zizemer

et al. 2019

Molecular Genetics and Metabolism Reports

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IntroductionGaucher disease (GD) type 1 is a lysosomal disease characterised by hepatosplenomegaly, anemia, thrombocytopenia, bone changes, and bone marrow infiltration. The disease is caused by biallelic pathogenic variants in GBA1 which codes for glucocerebrosidase, an enzyme involved in the catabolic pathway of complex lipids.AimsTo report on the case of two sisters with GD type 1 who bear a genotype never reported in the literature.Case reportPatient 1 is a 47-year-old female diagnosed at 42 years of age with chronic lumbar pain, mild splenomegaly, slightly reduced platelets and normal hemoglobin values, severe Bone Marrow Burden (BMB) score, high chitotriosidase activity, and low glucocerebrosidase. Patient 2 is a 50-year-old female, sister of patient 1, who was diagnosed after familial screening. At 45 years of age, she had osteonecrosis of the left femur and a total hysterectomy because of uncontrollable bleeding. At first evaluation, she had bone pain with a high BMB score, mild splenomegaly, normal hemoglobin, normal platelets count, elevated chitotriosidase activity, and low glucocerebrosidase activity. Both patients were found to be compound heterozygotes for the p.Glu388Lys and the p.Ser405Asn variants in GBA1.ConclusionsThis is the first family with GD and this combination of variants which causes a phenotype remarkable for severe bone disease with no or mild hematological manifestations.

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KIR genes and HLA class I ligands in Gaucher disease

Abstract: Although exploratory our data suggest a possible association of KIR/HLA variants and the severity of GD. Further study of KIR/HLA variants is required, as they seem to be a phenotype-modifying factor in this disease.

Cited by 5 publications

References 56 publications

The prognostic value of the serum ferritin in a southern Brazilian cohort of patients with Gaucher disease

The prognostic value of the serum ferritin in a southern Brazilian cohort of patients with Gaucher disease

Association between KIR genotypes and HLA-B alleles on viral load in Southern Brazilian individuals infected by HIV-1 subtypes B and C

Rare GBA1 genotype associated with severe bone disease in Gaucher disease type 1

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