Mutations of Bruton's tyrosine kinase gene in Brazilian patients with X-linked agammaglobulinemia

Ramalho, Vanessa Domingues; Júnior, Esmeraldina; Tani, Sergio Massayuki; Júnior, Pérsio Roxo; Vilela, M. M. S.

doi:10.1590/s0100-879x2010007500079

Cited by 7 publications

(3 citation statements)

References 17 publications

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“…BTK protein quantification was calculated by flow cytometry [8,28]. PBMC were removed from whole blood using Ficoll-Hypaque and later were stained with a phycoerythrinlabeled anti-CD14 (IgG2a; Dako, Japan) monoclonal antibody to separate monocytes.…”

Section: Flow Cytometry Analysis Of Btk Expressionmentioning

confidence: 99%

“…Mutations have been found in all BTK domains, being spread throughout the gene (http://bioinf.uta.fi/BTKbase) and have been reported in many different countries [6]. Our group has been the first to publish the diagnosis of XLA by analysis of mutations of the BTK gene in Brazilian patients [7,8]. Despite the large number of mutations identified, it has not been possible to correlate the genetic defect with the severity of the resulting clinical phenotype [9].…”

Section: Introductionmentioning

confidence: 99%

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BTK mutations selectively regulate BTK expression and upregulate monocyte XBP1 mRNA in XLA patients

Teocchi

Ramalho

Abramczuk

et al. 2015

Immunity Inflam & Disease

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Mutations in the Bruton agammaglobulinemia tyrosine kinase (BTK) gene are responsible for X-linked agammaglobulinemia (XLA). Unfolded or misfolded proteins can trigger stress pathways in the endoplasmic reticulum (ER), known as unfolded protein response (UPR). The aim was to clarify the involvement of UPR in XLA pathophysiology. By reverse transcription-quantitative PCR, we evaluated the expression of BTK and 12 UPR-related genes in eight patients. Moreover, we assessed the BTK protein expression and pattern in the patients' monocytes by flow cytometry and fluorescence immunocytochemistry. We found a reduced BTK expression in patients with stop codon mutations (P < 0.02). However, missense mutations did not affect BTK expression. Flow cytometry showed a reduction of BTK in patients which was corroborated by an absent or nonfunctional protein synthesis revealed by immunocytochemistry. In contrast with the other UPR-related genes, X-box binding protein 1 (XBP1) was markedly upregulated in the patients (P < 0.01), suggesting Toll-like receptor (TLR) activation since BTK directly interacts with TLRs as a negative regulator and XBP1 can be activated in direct response to TLR ligation. Different BTK mutations can be identified by the BTK expression. Inasmuch as UPR-related genes were downregulated or unaltered in patients, we speculate the involvement of the TLRs-XBP1 axis in the XLA pathophysiology. Such data could be the basis for further studies of this novel pathomechanism concerning XLA.

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Section: Flow Cytometry Analysis Of Btk Expressionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

BTK mutations selectively regulate BTK expression and upregulate monocyte XBP1 mRNA in XLA patients

Teocchi

Ramalho

Abramczuk

et al. 2015

Immunity Inflam & Disease

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show abstract

“…29 Our group has been the first to publish the molecular diagnosis of XLA in Brazilian patients. 30 , 31 Although it has not been possible to correlate the genetic defect with the severity of the clinical phenotype, 7 , 10 , 16 it is possible that the nonsense mutations directing to RNA decay may affect BTK expression with its hypoexpression. 32 …”

Section: Introductionmentioning

confidence: 99%

Human Inborn Errors of Immunity (HIEI): predominantly antibody deficiencies (PADs): if you suspect it, you can detect it

Vilela

2021

Jornal de Pediatria

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Protein Kinases and their Inhibitors Implications in Modulating Disease Progression

Ahsan,

Khan,

Mishra

et al. 2023

Protein J

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Mutations of Bruton's tyrosine kinase gene in Brazilian patients with X-linked agammaglobulinemia

Cited by 7 publications

References 17 publications

BTK mutations selectively regulate BTK expression and upregulate monocyte XBP1 mRNA in XLA patients

BTK mutations selectively regulate BTK expression and upregulate monocyte XBP1 mRNA in XLA patients

Human Inborn Errors of Immunity (HIEI): predominantly antibody deficiencies (PADs): if you suspect it, you can detect it

Protein Kinases and their Inhibitors Implications in Modulating Disease Progression

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