Single-Center Study of 72 Patients with Severe Combined Immunodeficiency: Clinical and Laboratory Features and Outcomes

Journal of Clinical Immunology - Severe combined immunodeficiency is an inborn error of immunity characterized by impairments in the numbers and functions of T and B lymphocytes due to various...     

Clinical Spectrum of LIG4 Deficiency Is Broadened with Severe Dysmaturity,Primordial Dwarfism,and Neurological Abnormalities

DNA double‐strand break repair via non‐homologous end joining (NHEJ) is involved in recombination of immunoglobulin and T‐cell receptor genes. Mutations in NHEJ components result in syndromes that are characterized by microcephaly and immunodeficiency. We present a patient with lymphopenia, extreme radiosensitivity, severe dysmaturity, corpus callosum agenesis, polysyndactily, dysmorphic appearance, and erythema, which are suggestive of a new type of NHEJ deficiency. We identified two heterozygous mutations in LIG4. The p.S205LfsX29 mutation results in lack of the nuclear localization signal and appears to be a null mutation. The second mutation p.K635RfsX10 lacks the C‐terminal region responsible for XRCC4 binding and LIG4 stability and activity, and therefore this mutant might be a null mutation as well or have very low residual activity. This is remarkable since Lig4 knockout mice are embryonic lethal and so far in humans no complete LIG4 deficiencies have been described. This case broadens the clinical spectrum of LIG4 deficiencies.     

Galactorrhea-associated granulosa cell tumor in a child

Granulosa cell tumor of the ovary is a rare form of ovarian cancer in children. An 11-year-old girl was admitted with complaints of galactorrhea and abdominal mass. Abdomino-pelvic ultrasound and computed tomography revealed an ovarian tumor. Her prolactine and estradiol levels were increased but luteinizing hormone and follicle-stimulating hormone were decreased. An exploratory laparotomy revealed a giant solid mass, which was completely removed and determined as juvenile granulosa cell tumor. The clinical, hormonal, and radiological findings and the therapy of galactorrhea associated with granulosa cell tumor in a child are discussed. To our knowledge, this is first time it has been described in childhood.     

Pulmonary arterial pressure in children with allergic rhinitis

BACKGROUND: Chronic upper airway obstruction may lead to increased pulmonary arterial pressure in childhood. Allergic rhinitis is one of the frequent causes of upper airway obstruction by nasal blockage. The aims of the study were to evaluate the pulmonary arterial pressures in children with allergic rhinitis and the effect of topical corticosteroid therapy. METHODS: Forty-nine children composed of 27 subjects with seasonal and 22 subjects with perennial allergic rhinitis were enrolled in this study. The pulmonary arterial pressures were measured by using Doppler echocardiography. RESULTS: The pretreatment pulmonary arterial systolic, mean, and diastolic pressures of study group were significantly higher than in healthy controls (p < 0.05). The pulmonary arterial systolic and mean pressures of the patient group significantly decreased at the end of study (p < 0.05), whereas the decrease of the diastolic pressure was not statistically significant (p > 0.05) after the treatment of a topical corticosteroid, mometasone furoate (100 microg per day), for 8 weeks. CONCLUSION: Our results showed that children with allergic rhinitis have higher pulmonary arterial pressure levels compared with healthy controls and that increased pulmonary arterial pressure levels due to allergic rhinitis are reversible by using nasal topical corticosteroids. Further studies are needed to determine the clinical aspect of increased pulmonary arterial pressure.     

Primary antibody deficiencies in Turkey: molecular and clinical aspects

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.

     

Correction to: Primary antibody deficiencies in Turkey: molecular and clinical aspects

Immunologic Research -     

Long-Term Experience of Subcutaneous Immunoglobulin Therapy in Pediatric Primary Immunodeficient Patients with Low and Normal Body Weight

Journal of Clinical Immunology - The aim was to review the compliance, side effects and effectiveness of subcutaneous immunoglobulin (SCIG) supplementation in patients with primary...     

Is the beneficial effect of preinfarction angina related to an immune response?

Immune-mediated mechanisms are thought to play a key role in the development of coronary artery disease and its thrombotic complications. Preinfarction angina has been suggested to improve left ventricular function and short-term outcomes. The purpose of the present study was to investigate the relation between the immune response and in-hospital clinical course in preinfarction angina. We prospectively evaluated 93 patients. Forty-three patients exhibited preinfarction angina within 24 hours before the onset of acute myocardial infarction (AMI) (preinfarction angina group) and 50 patients were free from preinfarction angina (sudden onset group). The incidence of complications (heart failure, recurrent angina, arrhythmia and coronary interventions) and in-hospital mortality were assessed in the two study groups. We detected some immune markers, including white blood cells, C-reactive protein, immunoglobulins, and complement. White blood cells and CRP were significantly lower in the preinfarction angina group than in the sudden onset group (P < 0.001, P < 0.005, respectively). Conversely, IgE and C(4) were significantly higher in the preinfarction angina group than in the sudden onset group (P < 0.001, P < 0.001, respectively). The incidences of heart failure and severe arrhythmias were lower in the preinfarction group than in the sudden onset group (P < 0.005, P < 0.05 respectively). The beneficial effect of preinfarction angina may be associated with an immune-inflammatory response modified by a brief ischemic episode.     

Cardiac troponin-I in the serum of infants of diabetic mothers

A transient form of hypertrophic cardiomyopathy has been previously described in infants of diabetic mothers. When it occurs, it is generally benign. The purpose of our study was to establish the extent of injury to the cardiomyocytes in symptomatic and asymptomatic patients with and without hypertrophic cardiomyopathy. Thus, we compared 35 consecutive patients to 20 healthy controls, establishing the significance, if any, of differences in cardiac troponin-I and creatine kinase, including its MB-fraction, and seeking to establish the value of these parameters in the diagnosis of cardiac injury. We also determined to levels of glucose and insulin in the serum, and took note of electrocardiographic and echocardiographic investigations. Values were determined at the 1st and 7th days after admission in the patients, while parameters were measured in the control group only on the first day. We found that the levels of cardiac troponin-I in the serum, known to be a marker for cardiac injury, were significantly elevated in symptomatic patients with life-threatening respiratory or haemodynamic distress. We speculate that transient ventricular hypertrophy is neither the cause nor the consequence of damage to the cardiomyocytes. It would be interesting, nonetheless, to determine the relationship, if any, between cardiomyocytic damage and clinical outcome.     

Effect of dexmedetomidine on haemodynamic responses to laryngoscopy and intubation : perioperative haemodynamics and anaesthetic requirements

BACKGROUND: Dexmedetomidine reduces the dose requirements for opioids and anaesthetic agents. The purpose of this study was to evaluate the effect of a single pre-induction intravenous dose of dexmedetomidine 1 microg/kg on cardiovascular response resulting from laryngoscopy and endotracheal intubation, need for anaesthetic agent and perioperative haemodynamic stability. METHODS: Fifty patients scheduled for elective minor surgery were randomised into two groups (dexmedetomidine group and placebo group, n = 25 in each group). During and after drug administration, the Ramsey sedation scale was applied every 5 minutes. Fentanyl 1 microg/kg was administered to all patients and thiopental was given until lash reflex disappeared. Anaesthesia continuation was maintained with 50% : 50%, oxygen : nitrous oxide. Sevoflurane concentration was adjusted to maintain systolic blood pressure within 20% of preoperative values. After extubation, the Steward awakening score was applied at 5 and 10 minutes. Haemodynamic parameters and adverse effects were recorded every 10 minutes for 1 hour after surgery. RESULTS: During intubation the need for thiopental and sevoflurane concentration were decreased by 39% and 92%, respectively, in the dexmedetomidine group compared with the placebo group. In all groups, blood pressure and heart rate increased after tracheal intubation; both were significantly lower in the dexmedetomidine group than in the placebo group (p < 0.05). Fentanyl requirement during the operation was 74.20 +/- 10.53microg in the dexmedetomidine group and 84.00 +/- 27.04microg in the placebo group (p < 0.05). At 5 minutes, the Steward scores were >6 in 56% of the dexmedetomidine group and in 4% of the placebo group (p < 0.05). At 10 minutes, sedation scores were > or =4 in all patients in the dexmedetomidine group (p < 0.05). Arterial blood pressure and heart rate in the postoperative period were significantly lower in the dexmedetomidine group compared with the placebo group (p < 0.05). CONCLUSION: Preoperative administration of a single dose of dexmedetomidine resulted in progressive increases in sedation, blunted the haemodynamic responses during laryngoscopy, and reduced opioid and anaesthetic requirements. Furthermore, dexmedetomidine decreased blood pressure and heart rate as well as the recovery time after the operation.