Dysregulation of unfolded protein response associated with common variable immunodeficiency. / A desregulação da via UPR associada à imunodeficiência comum variável.

AUTOR(ES)

Juliana Sayuri Kuribayashi

DATA DE PUBLICAÇÃO

2007

RESUMO

Common Variable Immunodeficiency (CVID) is characterized by hypogammaglobulinemia and recurrent infections. Herein we addressed the role of Unfolded Protein Response (UPR) in the pathogenesis of the disease. Augmented unspliced XBP-1 mRNA concurrent with co-localization of IgM and BiP was found in one CVID patient. Sequencing of RT-PCR amplicons did not reveal any mutation on XBP-1 neither on the kinase/endonuclease domains of IRE-1a. Q-PCR analysis of spliced XBP-1, IRE-1a and BiP after LPS or Brefeldin A treatment showed that, unlike healthy controls that respond to these ER stressors by presenting waves of transcription of these three genes, the cells presented lower rates of transcription, not reaching the same level of response of healthy subjects. Our findings associate diminished splicing of XBP-1 mRNA with accumulation of IgM within the ER and lower rates of chaperone transcription, therefore providing a mechanism to explain the observed hypogammaglobulinemia.

ASSUNTO(S)

retículimunodeficiência comum variávelo endoplasmático imunoglobulinas imunologia b cells common variable immunodeficiency unfolded portein response pathway endoplasmic reticulum linfócitos b via upr. immunoglobulins. immunology

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