ABSTRACT
The presence of autoantibodies to multiple-islet autoantigens confers high risk for the development of type 1 diabetes. Four major autoantigens are established (insulin, glutamate decarboxylase, IA2, and zinc transporter-8), but the molecular identity of a fifth, a 38-kDa membrane glycoprotein (Glima), is unknown. Glima antibodies have been detectable only by immunoprecipitation from extracts of radiolabeled islet or neuronal cells. We sought to identify Glima to enable efficient assay of these autoantibodies. Mouse brain and lung were shown to express Glima. Membrane glycoproteins from extracts of these organs were enriched by detergent phase separation, lectin affinity chromatography, and SDS-PAGE. Proteins were also immunoaffinity purified from brain extracts using autoantibodies from the sera of patients with diabetes before SDS-PAGE. Eluates from gel regions equivalent to 38 kDa were analyzed by liquid chromatography-tandem mass spectrometry for protein identification. Three proteins were detected in samples from the brain and lung extracts, and in the immunoaffinity-purified sample, but not in the negative control. Only tetraspanin-7, a multipass transmembrane glycoprotein with neuroendocrine expression, had physical characteristics expected of Glima. Tetraspanin-7 was confirmed as an autoantigen by demonstrating binding to autoantibodies in type 1 diabetes. We identify tetraspanin-7 as a target of autoimmunity in diabetes, allowing its exploitation for diabetes prediction and immunotherapy.
Subject(s)
Autoantibodies/immunology , Diabetes Mellitus, Type 1/immunology , Membrane Glycoproteins/immunology , Tetraspanins/immunology , Adolescent , Adult , Animals , Autoantibodies/blood , Autoantigens/immunology , Brain/immunology , Humans , Lung/immunology , Mice , Middle AgedABSTRACT
Disorders of sex development (DSD) encompass a range of conditions, and the management of infants with DSD can be extremely complex. However, the misdiagnosis of a normal infant as a case of DSD may lead to unfortunate long-term consequences for the individual and the family. We report a case of confined blood chimerism masking as 46 XY gonadal dysgenesis in a female from a twin pair with discordant genders, which led to incorrect sex determination at birth. The potentially serious consequences of a wrong DSD diagnosis are discussed, including the removal of normal ovaries. This case emphasises the importance of confirming a blood karyotype where there is discordance with the clinical phenotype and, where possible, identifying whether functional gonadal tissue is present.
Subject(s)
Chimerism , Diagnostic Errors , Gonadal Dysgenesis, 46,XY/diagnosis , Karyotype , Female , Gonadal Dysgenesis, 46,XY/blood , Humans , Karyotyping , PhenotypeABSTRACT
A 2-year-old boy with hypoplastic left heart syndrome and previous hemi-Fontan palliation surgery was referred for cardiovascular magnetic resonance evaluation because of progressive cyanosis. This case report illustrates the advantages of non-invasive four-dimensional magnetic resonance imaging for comprehensive identification and quantification of venovenous collaterals in patients with palliated hemi-Fontan staged surgery.
