ABSTRACT
PURPOSE: Mendelian susceptibility to mycobacterial disease is a rare clinical condition characterized by a predisposition to infectious diseases caused by poorly virulent mycobacteria. Other infections such as salmonellosis and candidiasis are also reported. The purpose of this article is to describe a young boy affected with various infectious diseases caused by Mycobacterium tuberculosis complex, Salmonella sp, Klebsiella pneumonie, Citrobacter sp., and Candida sp, complicated with severe enteropathy and transient hypogammaglobulinemia. METHODS: We reviewed medical records and performed flow cytometry staining for lymphocyte populations, lymphocyte proliferation in response to PHA, and intracellular IFN-γ production in T cell PHA blasts in the patient and a healthy control. Sanger sequencing was used to confirm the genetic variants in the patient and relatives. RESULTS: Genetic analysis revealed a bi-allelic mutation in IL12RB1 (C291Y) resulting in complete IL-12Rß1 deficiency. Functional analysis demonstrated the lack of intracellular production of IFN-γ in CD3+ T lymphocytes from the patient in response to rhIL-12p70. CONCLUSIONS: To our knowledge, this is the third patient with MSMD due to IL-12Rß1 deficiency complicated with enteropathy and hypogammaglobulinemia and the first case of this disease to be described in Colombia.
Subject(s)
Agammaglobulinemia/genetics , Candidiasis/genetics , Enteritis/genetics , Gram-Negative Bacterial Infections/genetics , Receptors, Interleukin-12/deficiency , Receptors, Interleukin-12/genetics , Agammaglobulinemia/drug therapy , BCG Vaccine , Candidiasis/drug therapy , Drug Resistance, Bacterial , Enteritis/drug therapy , Genetic Predisposition to Disease , Gram-Negative Bacterial Infections/drug therapy , Humans , Infant , Mutation , Mycobacterium tuberculosisABSTRACT
Los informes de la literatura apoyan el papel de la arginina como mecanismo regulador de la respuesta inmune. Se ha descrito la correlación entre disminución de la arginina y reducción de la proliferación y la activación de los linfocitos T en trasplante hepático, trauma grave, sepsis y cáncer. Entre los efectos se describen la disminución en la expresión de la cadena CD3z (traducción de la señal de activación en el linfocito T). La disminución de la arginina está relacionada con la producción de arginasa 1 (ARG1) por parte de las células mieloides supresoras. Se han propuesto dos posibles mecanismos por medio de los cuales el aumento de la actividad de ARG1 podría estar actuando en un proceso tumoral. El primero es la disminución de la proliferación de los linfocitos y el freno del ciclo celular. El segundo es promover el crecimiento tumoral al transformar la arginina en precursores de poliaminas. Se presentan en este artículo los principales conceptos del papel de la arginina en la respuesta antitumoral.
Recent findings support the potential role of arginine as a regulator of the immune response. Correlation between decreased arginine and decreased proliferation and activation of T lymphocytes has been described in liver transplantation, severe trauma, sepsis and cancer. Among the effects, decrease in the CD3z chain expression (activation signal in the T cell) has been described. Arginine is reduced in relation to the production of arginase 1 (ARG1) by myeloid suppressor cells. Two possible mechanisms have been postulated by which the increased activity of ARG1 could be acting on a tumor. The first is the reduction of lymphocyte proliferation and cell cycle arrest. The second is to promote tumor growth by transforming arginine in precursors of polyamines. We present in this article the main concepts on the role of arginine in antitumor response.
