Volume 5 • Number 2 • June 2018

Original Article

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Vol. 5No. 2pp. 35–47
Severe bacterial infection (SBI) poses a significant clinical problem as its mortality and morbidity is still unacceptably high. A systematic literature analysis was performed with an emphasis on recent meta analyses examining the specificity and sensitivity of conventional inflammation biomarkers (C-reactive protein, procalcitonin, interleukin-6, interleukin-8) for diagnosing SBI. Most inflammation biomarkers do not show high sensitivity and are of limited value regarding SBI detection. To the practicing clinician, the sole use of inflammation markers is not useful for differentiating between viral or bacterial origin of infection in an individual patient. Thus, only in combination with clinical biometric markers, taken from patient history and physical examination, is the analysis of inflammation biomarkers to some degree helpful in clinical practice. To date, their sensitivity and specificity have been best captured in the field of neonatology, where levels of interleukin-6 have been measured in combination with relevant perinatal factors. The indiscriminate use of inflammation biomarkers for the diagnosis of SBI may lead to over diagnosis. Novel technologies for pathogen detection and more precise measurement of the host-response using microarrays, allowing for simultaneous detection of multiple genes or proteins, promise to improve the value of laboratory biomarkers for the diagnosis of SBI.Statement of novelty: Presented here is an up-to-date systematic analysis of C-reactive protein and inflammation biomarkers with regard to their use in the diagnosis of SBI. I question whether a broad use of C-reactive protein is useful in patients presenting with infection. The results of the systematic analysis are put into context with recent concerns about over-diagnosing in medicine. This paper is adapted from a publication in the German journal Monatsschrift Kinderheilkunde.
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Vol. 5No. 2pp. 49–56
Background: Inherited defects in the function of the purine nucleoside phosphorylase (PNP) enzyme can cause severe T cell immune deficiency and early death from infection, autoimmunity, or malignancy. In addition, more than 50% of patients suffer diverse non-infectious neurological complications. However the cause for the neurological abnormalities are not known.Objectives: Differentiate induced pluripotent stem cells (iPSC) from PNP-deficient patients into neuronal cells to better understand the effects of impaired purine metabolism on neuronal development.Methods: Sendai virus was used to generate pluripotent stem cells from PNP-deficient and healthy control lymphoblastoid cells. Cells were differentiated into neuronal cells through the formation of embryoid bodies.Results: After demonstration of pluripotency, normal karyotype, and retention of the PNP deficiency state, iPSC were differentiated into neuronal cells. PNP-deficient neuronal cells had reduced soma and nuclei size in comparison to cells derived from healthy controls. Spontaneous apoptosis, determined by Caspase-3 expression, was increased in PNP-deficient cells.Conclusions: iPSC from PNP-deficient patients can be differentiated into neuronal cells, thereby providing an important tool to study the effects of impaired purine metabolism on neuronal development and potential treatments.Statement of novelty: We report here the first generation and use of neuronal cells derived from induced pluripotent stem cells to model human PNP deficiency, thereby providing an important tool for better understanding and management of this condition.
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Vol. 5No. 2pp. 57–60
Chronic granulomatous disease is a primary immunodeficiency disease caused by a genetic mutation in any of the 5 genes encoding the different components of the Nicotinamide Adenine Dinucleotide Phosphate reduced (NADPH)-Oxidase enzyme complex. Since primary immunodeficiency diseases are considered to be rare diseases, the genetic diagnosis of a certain primary immunodeficiency leads to the reasonable assumption that all patients with the same disease within the same family will have the same genetic mutation. We report 2 patients with chronic granulomatous disease from the same extended consanguineous family who had different genetic causes of their disease. Therefore, it is crucial to obtain a definitive genetic diagnosis of primary immunodeficiency disease even in patients from the same family, where the same genetic diagnosis is presumed to be the cause of the disease.Statement of novelty: Genetic causes of chronic granulomatous disease may be different in patients from the same family.

Protocols

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Vol. 5No. 2pp. 61–65
The identification of the genetic causes of Common Variable Immune Deficiency (CVID) has led to recognition of the need for biological medications to treat the autoimmune manifestations that CVID patients with LRBA and CTLA4 deficiency experience. Immunologists have not traditionally used biological medications as treatment in CVID patients and may not be familiar with the use of them. We present the process and protocol as well as a nursing checklist used by the Division of Rheumatology for the use of Abatacept.Statement of novelty: The methodology used to develop the order set and nursing checklist may be applied to other biologic medications as they become available.
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