Citations

Abstract The link between autoimmune diseases and primary immunodeficiency syndromes has been increasingly appreciated. Immunologic evaluation of a young man with autoimmune enterocolopathy and unexplained infections revealed evidence of immunodeficiency, including IgG subclass deficiency, impaired Ag-induced lymphocyte proliferation, reduced cytokine production by CD8+ T lymphocytes, and decreased numbers of NK cells. Genetic evaluation identified haploinsufficiency of NFAT5, a transcription factor regulating immune cell function and cellular adaptation to hyperosmotic stress, as a possible cause of this syndrome. Inhibition or deletion of NFAT5 in normal human and murine cells recapitulated several of the immune deficits identified in the patient. These results provide evidence of a primary immunodeficiency disorder associated with organ-specific autoimmunity linked to NFAT5 deficiency.

ABSTRACTBACKGROUND AND PURPOSEMild cognitive impairment (MCI) precedes both Alzheimer's disease (AD) dementia and with Lewy bodies (DLB). We investigated proton magnetic resonance spectroscopy (MRS) characteristics of MCI patients who progressed to DLB compared to those who progressed to AD dementia or remained stable.METHODSConsecutive MCI patients who underwent single voxel MRS at baseline and progressed to DLB (n = 10) were identified during a median follow‐up period of 18 months. From the same cohort, we identified age‐ and sex‐matched MCI patients who progressed to AD dementia (n = 27) or remained stable (n = 20) during a similar follow‐up period. This study was approved by the Institutional Review Board and informed consent was from every subject.RESULTSMCI patients who progressed to AD dementia were characterized by lower N‐acetylaspartate (NAA)/Cr ratio in the posterior cingulate voxel compared to those who progressed to DLB (P = .001). Decreased NAA/Cr in the posterior cingulate voxel differentiated MCI patients who progressed to DLB from those who progressed to AD with an area under the receiver operating characteristic curve of .85 (P < .001) on logistic regression analysis.CONCLUSIONSMRS may be useful in differentiating MCI patients with prodromal AD dementia from those with prodromal DLB for early disease‐specific interventions.

SummaryThe MRI technique diffusion tensor imaging (DTI) is reviewed along with microstructural changes associated with prodromal Alzheimer's disease (AD) as a potential biomarker for clinical applications. The prodromal stage of AD is characterized by mild cognitive impairment (MCI), representing a transitional state between normal aging and AD. Microstructural abnormalities on DTI are promising in vivo biomarkers of gray and white matter changes associated with the progression of AD pathology. Elevated mean diffusivity and decreased fractional anisotropy are consistently found in prodromal AD, and even in cognitively normal elderly who progress to MCI. However, quality of parameter maps may be affected by artifacts of motion, susceptibility, and eddy current‐induced distortions. The DTI maps are typically analyzed by region‐of‐interest or voxel‐based analytic techniques such as tract‐based spatial statistics. DTI‐based index of diffusivity is complementary to macrostructural gray matter changes in the hippocampus in detecting prodromal AD. Breakdown of structural connectivity measured with DTI may impact cognitive performance during early AD. Furthermore, assessment of hippocampal connections may help in understanding the cerebral organization and remodeling associated with treatment response.