Personalized medicine approach in mycobacterial disease

Mirsaeidi, Mehdi

doi:10.1016/j.ijmyco.2012.03.001

Cited by 8 publications

(7 citation statements)

References 38 publications

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“…A confirmed molecular diagnosis directs potential treatment approaches such as the indication for stem cell therapy. Moreover, genetic predisposition combined with protein dysfunction studies are already used to tailor-make patient-specific approaches in mycobacterial disease ( 49 ). In the era of personalized medical treatment, based on unique genetic features, it is realistic to anticipate that this will also be extended to the specific treatment of variants of genetically susceptible TB.…”

Section: Discussionmentioning

confidence: 99%

Exome Sequencing Identifies a Novel MAP3K14 Mutation in Recessive Atypical Combined Immunodeficiency

et al. 2017

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Primary immunodeficiency disorders (PIDs) render patients vulnerable to infection with a wide range of microorganisms and thus provide good in vivo models for the assessment of immune responses during infectious challenges. Priming of the immune system, especially in infancy, depends on different environmental exposures and medical practices. This may determine the timing and phenotype of clinical appearance of immune deficits as exemplified with early exposure to Bacillus Calmette-Guérin (BCG) vaccination and dissemination in combined immunodeficiencies. Varied phenotype expression poses a challenge to identification of the putative immune deficit. Without the availability of genomic diagnosis and data analysis resources and with limited capacity for functional definition of immune pathways, it is difficult to establish a definitive diagnosis and to decide on appropriate treatment. This study describes the use of exome sequencing to identify a homozygous recessive variant in MAP3K14, NIKVal345Met, in a patient with combined immunodeficiency, disseminated BCG-osis, and paradoxically elevated lymphocytes. Laboratory testing confirmed hypogammaglobulinemia with normal CD19, but failed to confirm a definitive diagnosis for targeted treatment decisions. NIKVal345Met is predicted to be deleterious and pathogenic by two in silico prediction tools and is situated in a gene crucial for effective functioning of the non-canonical nuclear factor-kappa B signaling pathway. Functional analysis of NIKVal345Met- versus NIKWT-transfected human embryonic kidney-293T cells showed that this mutation significantly affects the kinase activity of NIK leading to decreased levels of phosphorylated IkappaB kinase-alpha (IKKα), the target of NIK. BCG-stimulated RAW264.7 cells transfected with NIKVal345Met also presented with reduced levels of phosphorylated IKKα, significantly increased p100 levels and significantly decreased p52 levels compared to cells transfected with NIKWT. Ideally, these experiments would have been conducted in patient-derived immune cells, but we were unable to source these cells from the patient. The functional analysis described in this paper supports previous illustrations of the importance of NIK in human immune responses and demonstrates the involvement of function-altering mutations in MAP3K14 in PIDs. The genomic approach used for this patient demonstrates its value in the diagnosis of an unusual PID and as a tool for detecting rarer mutations to help guide treatment approaches.

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Section: Discussionmentioning

confidence: 99%

Exome Sequencing Identifies a Novel MAP3K14 Mutation in Recessive Atypical Combined Immunodeficiency

et al. 2017

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“…Genetic abnormalities in the cell immunity pathway like interleukin-12/interferon-γ synthesis, cystic fibrosis transmembrane conductance regulator (CFTR) mutations, human leukocyte antigen (HLA) alleles, polymorphisms of solute carrier 11A1, and the vitamin D receptor cause increased vulnerability to systemic NTM disease [42–45]. Impaired IFN-gamma pathway such as IFN-γ deficiency may also play a role for increasing susceptibility to NTM [46–48].…”

Section: Methodsmentioning

confidence: 99%

Management of nontuberculous mycobacterial infection in the elderly

Mirsaeidi

Farshidpour

Ebrahimi

et al. 2014

European Journal of Internal Medicine

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The incidence of nontuberculous mycobacteria (NTM) has increased over the last decades. Elderly people are more susceptible to NTM and experience increased morbidities. NTM incidence is expected to rise due to an increasing elderly population at least up to 2050. Given the importance of NTM infection in the elderly, an increasing interest exists in studying NTM characteristics in aged population. In this review, we summarize the characteristics of NTM infection among elderly patients. We focus on epidemiology, clinical presentation, and treatment options of NTM in this age group. We highlight the differences in the diagnosis and treatment between rapid and slow growing mycobacterial infections. The current recommendation for treatment of NTM is discussed. We debate if in vitro susceptibility testing has a role in treatment of NTM. Drug-drug interaction between antibiotics used to treat NTM and other medications, particularly warfarin, is another important issue that we discuss. Finally, we review the prognosis of NTM disease in elderly patients.

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“…Even in seemingly normal hosts, some level of immunodeficiency or preexistent pulmonary disease probably exists [38]. Four categories of susceptible persons for NTM infection have been identified [23].…”

Section: Pathogenesis and Risk Factorsmentioning

confidence: 99%

“…Although for this reason NTM are considered opportunistic pathogens, they frequently cause infection in patients with no known underlying diseases. Even in seemingly normal hosts, some level of immunodeficiency or preexistent pulmonary disease probably exists [ 38 ]. Four categories of susceptible persons for NTM infection have been identified [ 23 ].…”

Section: Pathogenesis and Risk Factorsmentioning

confidence: 99%

Highlight on Advances in Nontuberculous Mycobacterial Disease in North America

Mirsaeidi

Farshidpour

Allen

et al. 2014

BioMed Research International

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Nontuberculous mycobacteria (NTM) are ubiquitous in the environment and exist as an important cause of pulmonary infections in humans. Pulmonary involvement is the most common disease manifestation of NTM and the incidence of NTM is growing in North America. Susceptibility to NTM infection is incompletely understood; therefore preventative tools are not well defined. Treatment of pulmonary nontuberculous mycobacterial (NTM) infection is difficult and entails multiple antibiotics and an extended treatment course. Also, there is a considerable variation in treatment management that should be considered before initiating treatment. We highlight the new findings in the epidemiology diagnosis and treatment of mycobacterial infections. We debate new advances regarding NTM infection in cystic fibrosis patients and solid organ transplant recipients. Finally, we introduce a new epidemiologic model for NTM disease based on virulence-exposure-host factors.

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Personalized medicine approach in mycobacterial disease

Cited by 8 publications

References 38 publications

Exome Sequencing Identifies a Novel MAP3K14 Mutation in Recessive Atypical Combined Immunodeficiency

Exome Sequencing Identifies a Novel MAP3K14 Mutation in Recessive Atypical Combined Immunodeficiency

Management of nontuberculous mycobacterial infection in the elderly

Highlight on Advances in Nontuberculous Mycobacterial Disease in North America

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