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Inorg Chem ; 57(2): 633-640, 2018 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-29278324


Two new, isostructural members of the title material class, [PPh4]4[Cu2Bi2I12] (1) and [PPh4]4[Ag2Bi2I12] (2), have been prepared via a facile solution route. The crystal structure of both compounds features a tetranuclear [M2Bi2I12]4- (M = Cu, Ag) anion that displays an unprecedented face-sharing mode of connection between BiI6 octahedra and MI4 tetrahedra, enabling close Bi···M contacts. The two compounds allow for a direct experimental and quantum chemical investigation of the influence of group 11 metal cations on the optical and electronic properties of ternary iodido bismuthate anions, indicating that Cu+ is a better electronic match than Ag+, resulting in a significantly lower optical band gap of the copper compound.

Front Immunol ; 8: 964, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28861081


BACKGROUND: Inducible co-stimulator (ICOS) deficiency was the first monogenic defect reported to cause common variable immunodeficiency (CVID)-like disease in 2003. Since then, 16 patients have been reported worldwide with an increasing range of clinical phenotypes. OBJECTIVE: We sought to compare the clinical and immunological phenotype and provide clinical follow-up and therapeutic approaches for treating ICOS-deficient patients. METHODS: We describe the clinical and laboratory data of 15 patients with available clinical data. Previous publications and clinical assessment were used as data sources. RESULTS: The observed ICOS gene mutations were all deletions leading to undetectable protein expression. The clinical phenotype of ICOS deficiency is much broader than initially anticipated and includes not only CVID-like disease but an increased susceptibility to viral and opportunistic infections, as well as cancer. Impaired B-cell development led to decreased memory B-cells in all patients, and hypogammaglobulinemia in all but one patient. Circulating CXCR5+ CD4+ follicular T-helper-cell numbers were also reduced in all patients. Treatment included immunoglobulin replacement, regular antibiotic prophylaxis, corticosteroids, and steroid-sparing agents. Three patients underwent hematopoietic stem cell transplantation; one of them died due to capillary leak syndrome on day 5 posttransplantation. CONCLUSION: The disease spectrum of ICOS deficiency is expanding from solely B-cell to combined B- and T-cell immunodeficiency, suggesting genetic and environmental modifiers. Genetic diagnosis is the only tool to distinguish ICOS deficiency from other immunological defects. Patients with antibody deficiency, autoimmunity, and combined immunodeficiency should be screened for ICOS mutations.

Arthritis Rheumatol ; 69(8): 1689-1700, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28493328


OBJECTIVE: We aimed to test the relevance of deficiency of adenosine deaminase 2 (DADA2) in patients with antibody deficiency and describe the clinical picture of the disease in adulthood. METHODS: We screened for DADA2 in a cohort of 181 patients with antibody deficiency with or without vascular lesions using next-generation sequencing and targeted Sanger sequencing. All mutations were confirmed by determining the ADA2 enzymatic activity levels in dried plasma spots. Clinical data and laboratory values were collected in a standardized format. RESULTS: Following the diagnosis of 2 siblings in the index family, we identified 9 additional affected patients with compound heterozygous or homozygous CECR1 mutations, containing 6 novel and 4 previously published mutations. The patients' age at evaluation ranged from 13 to 51 years, with a median age of 22 years. Clinically, we saw a broad phenotype, ranging from isolated antibody deficiency to recurrent strokes. All but 1 patient had low numbers of memory B cells. Moreover, B cell function seemed to correlate with inflammation. CONCLUSION: Taken together, our findings indicate that DADA2 presents not only with vasculopathy but also with an immunodeficiency of the B cell compartment. Therefore, patients with antibody deficiency should be screened for DADA2. Anti-tumor necrosis factor treatment might improve immunologic features over time and might be considered in patients without vascular manifestations but with elevated inflammation markers. Conservative management has so far proven to be the choice for our less severely affected adolescent and adult DADA2 patients; however, in patients with severe cytopenias and bone marrow failure, hematopoietic stem cell transplantation should be considered.

Adenosina Desaminase/genética , Síndromes de Imunodeficiência/genética , Peptídeos e Proteínas de Sinalização Intercelular/genética , Acidente Vascular Cerebral/genética , Adenosina Desaminase/imunologia , Adenosina Desaminase/metabolismo , Adolescente , Adulto , Linfócitos B/imunologia , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Homozigoto , Humanos , Síndromes de Imunodeficiência/imunologia , Peptídeos e Proteínas de Sinalização Intercelular/imunologia , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Mutação , Fenótipo , Análise de Sequência de DNA , Doenças Vasculares/genética , Adulto Jovem
J Clin Immunol ; 36(3): 179-86, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26922074


PURPOSE: Determining the monogenic cause of antibody deficiency and immune dysregulation in a non-consanguineous family with healthy parents, two affected children, and one unaffected child. METHODS: Whole Exome Sequencing (WES) was performed in the index family. WES results were confirmed by Sanger Sequencing. Dried plasma spots of the male patient and his mother were analyzed for ADA2 enzymatic activity. RESULTS: Following data analysis of WES, we found a compound heterozygous mutation in CECR1 (encoding adenosine deaminase 2, ADA2) that segregated in the two affected children. Enzyme activity measurement confirmed a severely diminished ADA2 activity in our patient. The 32 year old index patient was suffering from recurrent respiratory infections and was previously diagnosed with common variable immunodeficiency (CVID), showing no signs of vasculitis. His sister had a systemic lupus erythematosus (SLE)-like phenotype and died at age 17. CONCLUSIONS: Deficiency of ADA2 (DADA2) has been reported to cause vasculopathy and early-onset stroke. Our case suggests that it should also be considered when evaluating patients with antibody deficiencies and immune dysregulation syndromes.

Adenosina Desaminase/deficiência , Imunodeficiência de Variável Comum/diagnóstico , Imunoglobulina A/genética , Imunoglobulina G/genética , Peptídeos e Proteínas de Sinalização Intercelular/deficiência , Adenosina Desaminase/genética , Adolescente , Adulto , Criança , Imunodeficiência de Variável Comum/genética , Imunodeficiência de Variável Comum/patologia , Teste em Amostras de Sangue Seco , Exoma , Feminino , Expressão Gênica , Heterozigoto , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Peptídeos e Proteínas de Sinalização Intercelular/genética , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/patologia , Masculino , Mutação , Linhagem , Fenótipo