Complete IFN-gamma receptor ligand-binding chain (IFNgammaR1) deficiency is a life-threatening autosomal recessive immune disorder. Affected children invariably die of mycobacterial infection, unless bone marrow transplantation is undertaken. Pathogenic IFNGR1 mutations identified to date include nonsense and splice mutations and frameshift deletions and insertions. All result in a premature stop codon upstream from the segment encoding the transmembrane domain, precluding cell surface expression of the receptors. We report herein two sporadic and two familial cases of a novel form of complete IFNgammaR1 deficiency in which normal numbers of receptors are detected at the cell surface. Two in-frame deletions and two missense IFNGR1 mutations were identified in the segment encoding the extracellular ligand-binding domain of the receptor. Eight independent IFNgammaR1-specific mAb's, including seven blocking antibodies, gave recognition patterns that differed between patients, suggesting that different epitopes were altered by the mutations. No specific binding of (125)I-IFN-gamma to cells was observed in any patient, however, and the cells failed to respond to IFN-gamma. The mutations therefore cause complete IFNgammaR1 deficiency by disrupting the IFN-gamma-binding site without affecting surface expression. The detection of surface IFNgammaR1 molecules by specific antibodies, including blocking antibodies, does not exclude a diagnosis of complete IFNgammaR1 deficiency. 相似文献
Primary antibody deficiencies (PAD) are the most common subtype of primary immunodeficiencies, characterized by increased susceptibility to infections and autoimmunity, allergy, or malignancy predisposition. PAD syndromes comprise of immune system genes highlighted the key role of B cell activation, proliferation, migration, somatic hypermutation, or isotype switching have a wide spectrum from agammaglobulinemia to selective Ig deficiency. In this study, we describe the molecular and the clinical aspects of fifty-two PAD patients. The most common symptoms of our cohort were upper and lower respiratory infections, bronchiectasis, diarrhea, and recurrent fever. Almost all patients (98%) had at least one of the symptoms like autoimmunity, lymphoproliferation, allergy, or gastrointestinal disease. A custom-made next-generation sequencing (NGS) panel, which contains 24 genes, was designed to identify well-known disease-causing variants in our cohort. We identified eight variants (15.4%) among 52 PAD patients. The variants mapped to BTK (n?=?4), CD40L (n?=?1), ICOS (n?=?1), IGHM (n?=?1), and TCF3 (n?=?1) genes. Three novel variants were described in the BTK (p.G414W), ICOS (p.G60*), and IGHM (p.S19*) genes. We performed Sanger sequencing to validate pathogenic variants and check for allelic segregation in the family. Targeted NGS panel sequencing can be beneficial as a suitable diagnostic modality for diagnosing well-known monogenic PAD diseases (only 2–10% of PADs); however, screening only the coding regions of the genome may not be adequately powered to solve the pathogenesis of PAD in all cases. Deciphering the regulatory regions of the genome and better understanding the epigenetic modifications will elucidate the molecular basis of complex PADs.
Actinomycotic infections of the cervicofacial region are not uncommon. However, actinomycosis of the tongue is rare. A mass that may mimic both benign and malignant neoplasms can be seen at clinical presentation and may mislead the diagnosis. We report a patient who presented with a tumour-like tongue mass causing speech disturbance, diagnosed as actinomycosis. 相似文献
Before use of the pneumococcal conjugate vaccine PCV7 became widespread in Turkey, 202 invasive pneumococcus isolates were analyzed. The most common serotypes were 19F and 6B. In children ≤2 years of age, the potential coverage rate of PCV7 was 69.5%. The most frequent non-PCV7 serotypes were 19A, 3, 1, 6A, and 8. 相似文献
Systemic lupus erythematosus (SLE) is a rheumatologic disease characterized by an inflammatory destruction of the target organ systems of the body in an unknown way by autoantibodies formed against self-antigens. Infectious agents like Epstein–Barr virus (EBV), cytomegalovirus and parvovirus B19 may have a role in the occurrence or the exacerbation of the SLE. In this report, the clinical follow-up of a 14-year-old girl diagnosed with SLE following an EBV infection with bicytopenia, lymphadenomegaly and hepatomegaly is discussed. This case could support the role of viral infections in the etiology of SLE. 相似文献
BACKGROUND: This study aims to determine the relation between anabolic hormones, Insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 (IGFBP-3), growth parameters, and clinical status in prepubertal cystic fibrosis (CF) patients. This prospective study comprises age/sex-matched control subjects and was set in a tertiary care teaching hospital. METHODS: Serum concentrations of IGF-I and IGFBP-3 were measured in 37 CF and 23 healthy subjects, whose mean ages were 5.02 +/- 3.06 and 5.27 +/- 2.82, respectively. The results were analyzed in relation to body mass index standard deviation scores (BMISD), height standard deviation scores (HSD), growth velocity standard deviation scores (GVSD), and clinical status assessed by Shwachman scores and pulmonary function parameters. RESULTS: Serum IGFBP-3 of CF patients showed significantly lower concentrations than healthy subjects (2457 vs. 3249 ng/mL) (P < 0.05), whereas IGF-I levels did not (123.35 vs. 149.8 ng/mL). There was significant positive correlation between IGF-I and IGFBP-3 with HSD (r = 0.62; r = 0.79) and BMISD (r = 0.39; r = 0.50). The pulmonary function tests in 14 CF subjects were not statistically worse than in nine healthy cases. The mean HSD (-0.67, SD 1.06) and BMISD (-0.28, SD 0.71) of CF patients were not significantly lower than those of healthy subjects (-0.02, SD 0.86 and 0.03, SD 0.49), respectively. CONCLUSION: Decreased serum IGF-I and IGFBP-3 levels may reflect growth retardation in CF. IGFBP-3 seems like a more sensitive parameter than IGF-I for growth monitoring in this study. Growth parameters of Turkish prepubertal CF patients are not markedly below national standards. Different genetic backgrounds of relevant populations certainly play an important role for the variable clinical course. 相似文献