Interaction between a serum factor and T lymphocytes in gaucher disease

Bassan, Renato; Montanelli, Alessandro; Barbui, Tiziano

doi:10.1002/ajh.2830180407

Cited by 21 publications

(11 citation statements)

References 13 publications

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“…It has been postulated that progressive glucocerebroside accumulation may cause chronic stimulation of the immune system and consequent lymphoproliferation [32]. Ferritin release from Gaucher cells has been identified as involved in reducing T-cell function and immunoglobulin M release from B-cells [33]. …”

Section: Discussionmentioning

confidence: 99%

Mapping the genetic and clinical characteristics of Gaucher disease in the Iberian Peninsula

Giraldo

Alfonso

Irún

et al. 2012

Orphanet J Rare Dis

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BackgroundGaucher disease (GD) is due to deficiency of the glucocerebrosidase enzyme. It is panethnic, but its presentation reveals ethnicity-specific characteristics.MethodsWe evaluated the distribution, and clinical and genetic characteristics of GD patients in the Iberian Peninsula (IP). We analysed geographical distribution, demographic, genetic and clinical data, age at diagnosis, type, and years of therapy in 436 GD patients from the IP.ResultsThe prevalence of GD was 1/149,000 inhabitants; 88.3% were type 1, 6.7% type 2, and 5.0% type 3. The mean age at diagnosis in type 1 was 28.7 years. A total of 72.7% were classified as having mild forms, 25.5% moderate, and 1.7% severe. Anemia and thrombocytopenia were present in 56% and 55%, respectively. Bone disease and hepatomegaly were reported in 62% and 68%, respectively, and were more likely in asplenic than in non-splenectomized patients. Sixty-nine mutant alleles were identified, and five mutations accounted for 75% of the GBA alleles. Several patients described in our series had interesting phenotypes. A total of 58.7% of patients had received enzyme replacement therapy and 12.6% were treated with miglustat.ConclusionsA broad spectrum of GBA mutations is present in the IP, with 98.2% of type 1 GD being mild and 23.0% never treated. These data highlight genetic and phenotypic heterogeneities among geographic populations.

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Section: Discussionmentioning

confidence: 99%

Mapping the genetic and clinical characteristics of Gaucher disease in the Iberian Peninsula

Giraldo

Alfonso

Irún

et al. 2012

Orphanet J Rare Dis

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“…Deficiency of lysosomal GCase in GD leads to progressive accumulation of glucocerebroside and glucosylsphingosine in the lysosomes of tissue macrophages. It seems evident that lysosomal lipids eventually exit the lysosomal compartment [22] and thereby trigger macrophage activation and subsequent engagement of the innate and adaptive immune system [23][24][25][26]. Frequent occurrence of gammopathies in GD suggests chronic stimulation of the immune system and consequent lymphoproliferation [27,28].…”

Section: Discussionmentioning

confidence: 99%

Expanding spectrum of the association between Type 1 Gaucher disease and cancers: A series of patients with up to 3 sequential cancers of multiple types—Correlation with genotype and phenotype

Stein

Mullaly³

et al. 2010

American J Hematol

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In Gaucher disease (GD), inherited deficiency of lysosomal glucocerebrosidase due to mutations in GBA1 gene results in accumulation of glucosylceramide in tissue macrophages, systemic macrophage activation, and a complex multisystemic phenotype. We and others have reported an increased risk of multiple myeloma and other malignancies in non-neuronopathic Type 1 GD (GD1). Here, we describe a subset of GD1 patients with multiple malignancies. In our cohort of 403 patients with GD1, nine patients (2.2%) developed two or three different types of cancers either consecutively or simultaneously. Patients were characterized by age at diagnosis of GD1, GBA1 genotype, disease severity, age at cancer diagnosis, enzyme replacement therapy (ERT) status, and splenectomy status. Of the nine patients, six developed two types of malignancies and three had three cancers each. Overall, the hematologic malignancies comprised lymphoma/leukemia (4) and multiple myeloma (4). Nonhematologic malignancies included colon (2), lung (2), thyroid (2), and prostate cancer (1). Of the seven patients who received ERT, the first cancer was diagnosed before initiation of ERT in all but one. Asplenic patients were more likely to have single or multiple cancers compared with patients with intact spleens (P < 0.0072 and P < 0.0203, respectively). Our data strengthen the association of GD1 and cancer and suggest that patients may be at risk of developing multiple malignancies. We found an association between splenectomy and multiple cancers in GD1. It will be of interest to determine whether timely ERT and declining rates of splenectomy will translate into declining rates of multiple and single cancers. Am. J. Hematol. 85:340-345, 2010. V

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“…48 Ferritin release from Gaucher cells has been implicated in reducing T-cell function and immunoglobulin M (IgM) release from B cells. 49 Interleukin 6 (IL-6) is a significant putative signal transduction cytokine in multiple myeloma, 50 and IL-6 levels are increased in some patients with Gaucher disease. 51 Although recent histochemical analysis of GD splenic tissue suggests that classic Gaucher cells most closely resemble anti-inflammatory alternatively activated macrophages and do not produce typical proinflammatory molecules, there is nonetheless variable expression of IL-6 by Gaucher cells which also appear to induce a vigorous inflammatory response in surrounding classically activated red pulp macrophages.…”

Section: Discussionmentioning

confidence: 99%

Gaucher disease and cancer incidence: a study from the Gaucher Registry

Rosenbloom

Weinreb

Zimran

et al. 2005

Blood

216

187

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Patients with Gaucher disease (GD) are alleged to be at an increased risk of malignant disorders, possibly due to potential chronic stimulation of the immune system and lymphoproliferation associated with storage of glucocerebroside in tissue macrophages. Because previous reports of increased risk of malignancy in GD may have been affected by small patient numbers and ascertainment bias, 2742 patients with GD from the International Gaucher Registry were studied. The number of cancers identified among patients in the registry was compared with that expected in the US population of similar attained age and sex. The majority of patients were young or middle-aged adults at the time of last follow-up, with only 14% older than age 60. There were 10 patients with multiple myeloma, yielding an estimated relative risk of 5.

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Interaction between a serum factor and T lymphocytes in gaucher disease

Cited by 21 publications

References 13 publications

Mapping the genetic and clinical characteristics of Gaucher disease in the Iberian Peninsula

Mapping the genetic and clinical characteristics of Gaucher disease in the Iberian Peninsula

Expanding spectrum of the association between Type 1 Gaucher disease and cancers: A series of patients with up to 3 sequential cancers of multiple types—Correlation with genotype and phenotype

Gaucher disease and cancer incidence: a study from the Gaucher Registry

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