Allergic and Immunologic Parameters in Patients with Fanconi`s Anemia

Roxo, Pérsio; Arruda, L. Karla; Nagao, A. T.; Carneiro-Sampaio, Magda; Ferriani, Virgínia Paes Leme

doi:10.1159/000053837

Cited by 11 publications

(9 citation statements)

References 18 publications

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“…Prior publications suggested that immunoglobulins were decreased 15 or normal 10,16 in patients with FA, but did not separate children and adults or adjust for other variables. In our study, most children with FA had normal levels of immunoglobulins, while half of the adults had decreased levels.…”

Section: Discussionmentioning

confidence: 99%

Immune status of patients with inherited bone marrow failure syndromes

et al. 2015

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Immune function abnormalities have been reported in patients with Fanconi anemia (FA), dyskeratosis congenita (DC) and, rarely, in Shwachman-Diamond syndrome (SDS) and Diamond-Blackfan anemia (DBA), but large systematic studies are lacking. We assessed immunological parameters in 118 patients with these syndromes and 202 unaffected relatives. We compared results in patients with reference values, and with values in relatives after adjusting for age, sex, corticosteroid-treatment and severe bone marrow failure (BMF). Adult patients (≥18 years) with FA had significantly lower immunoglobulins (IgG, IgA and IgM), total lymphocytes and CD4 T-cells than reference values or adult relatives (p<0.001); children with FA had normal values. Both children and adults with FA had lower B- and NK-cells (p<0.01) than relatives or reference values. Patients with DC had essentially normal immunoglobulins but lower total lymphocytes than reference values or relatives, and lower T-, B- and NK-cells; these changes were more marked in children than adults (p<0.01). Most patients with DBA and SDS had normal immunoglobulins and lymphocytes. Lymphoproliferative responses, serum cytokine levels, including TNF-α and IFN-γ, and cytokine levels in supernatants from phytohemagglutinin-stimulated cultures were similar across patient groups and relatives. Only patients with severe BMF, particularly those with FA and DC, had higher serum G-CSF and Flt3-ligand and lower RANTES levels compared with all other groups or relatives (p<0.05). Overall, immune function abnormalities were seen mainly in adult patients with FA, which likely reflects their disease-related progression, and in children with DC, which may be a feature of early-onset severe disease phenotype.

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Section: Discussionmentioning

confidence: 99%

Immune status of patients with inherited bone marrow failure syndromes

et al. 2015

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“…Of note, some studies concerning the immunological response of FA patients demonstrated lymphocyte dysfunction and high levels of TNF-α [45]. Low production of IL including IL1, IL2, and IL6, as well as IFN-γ and granulocyte-macrophage colony stimulating factor have also been reported [46]. …”

Section: Discussionmentioning

confidence: 99%

Improvement of genetic stability in lymphocytes from Fanconi anemia patients through the combined effect of α-lipoic acid and N-acetylcysteine

Ponte

Sousa

Fernandes

et al. 2012

Orphanet J Rare Dis

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Fanconi Anemia (FA) is a rare genetic disorder, characterized by progressive bone marrow failure and increased predisposition to cancer. Despite being highly heterogeneous, all FA patients are hypersensitive to alkylating agents, in particular to 1,2:3,4-diepoxybutane (DEB), and to oxidative damage. Recent studies point to defective mitochondria in FA cells, which is closely related with increased production of reactive oxygen species (ROS) and concomitant depletion of antioxidant defenses, of which glutathione is a well-known biomarker.The objective of the present work is to evaluate the putative protective effect of α-lipoic acid (α-LA), a mitochondrial protective agent, and N-acetylcysteine (NAC), a direct antioxidant and a known precursor for glutathione synthesis, in spontaneous and DEB-induced chromosome instability (CI) in lymphocyte cultures from FA patients.For that purpose, lymphocyte cultures from 15 FA patients and 24 healthy controls were pre-treated with 20 μM α-LA, 500 μM NAC and α-LA plus NAC at the same concentrations, and some of them were exposed to DEB (0.05 μg/ml). A hundred metaphases per treatment were scored to estimate the relative frequency of spontaneous and DEB-induced chromosome breakage.The obtained results revealed that a cocktail of α-LA and NAC can drastically improve the genetic stability in FA lymphocytes in vitro, decreasing CI by 60% and 80% in cultures from FA patients and FA mosaic/chimera patients, respectively. These results suggest that the studied cocktail can be used as a prophylactic approach to delay progressive clinical symptoms in FA patients caused by CI, which can culminate in the delay of the progressive bone marrow failure and early cancer development.

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“…Along with lymphocyte dysfunction (Froom et al , 1987; Petridou & Barrett, 1990; Lebbe et al , 1993), high levels of tumour necrosis factor alpha (TNF-α) (Schultz & Shahidi, 1993; Rosselli et al , 1994), and low production of interleukins (IL) including IL1, IL2, and IL6, as well as interferon gamma (IFN-γ) and granulocyte-macrophage colony stimulating factor (GM-CSF) have also been reported (Roxo et al , 2001). In this study we performed a systematic assessment of adaptive immunity in 10 children with FA.…”

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confidence: 99%

Impaired immune function in children with Fanconi anaemia

Myers¹,

Bleesing²,

Davies³

et al. 2011

Br J Haematol

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Summary Fanconi anaemia is an autosomal recessive or X-linked disease characterized by progressive bone marrow failure, variable congenital abnormalities and a predisposition to malignancy. Reports of immune function in this population are limited, and include only specific areas of immune performance, showing variable defects. We report a cross-sectional immunological assessment in 10 children with FA. Absolute numbers of B cells and natural killer (NK) cells were reduced compared to controls (P = 0·048 and P = 0·0002, respectively), while absolute number of T cells were within normal range. Perforin and granzyme content of NK cells was reduced (P < 0·00001 and P = 0·0057, respectively) along with the NK cell cytotoxicity (P < 0·001). Antigen proliferation in response to tetanus was decreased (P = 0·008) while responses to candida and phytohaemagglutinin were not. Cytotoxic T cell function was also reduced (P < 0·0001). Immunoglobulin G levels were normal in those evaluated. Our series represents the first attempt at a comprehensive quantitative and functional evaluation of immune function in this rare group of patients and demonstrates a significant deficit in the NK cell compartment, a novel quantitative B cell defect, along with abnormal cytotoxic function. These findings may be especially relevant in this patient population with known predisposition to DNA damage and malignancy.

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Allergic and Immunologic Parameters in Patients with Fanconi`s Anemia

Cited by 11 publications

References 18 publications

Immune status of patients with inherited bone marrow failure syndromes

Immune status of patients with inherited bone marrow failure syndromes

Improvement of genetic stability in lymphocytes from Fanconi anemia patients through the combined effect of α-lipoic acid and N-acetylcysteine

Impaired immune function in children with Fanconi anaemia

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