De novo NFκB2 gene mutation associated common variable immunodeficiency / 中华儿科杂志

Objective@#To investigate the clinical, immunological, and molecular manifestations of nuclear factor kappa-B subunit 2 (NFκB2) gene mutation associated common variable immunodeficiency (CVID) .@*Methods@#A 14-month-old boy diagnosed with NFκB2-mutated CVID was admitted into Children's Hospital of Chongqing Medical University in December 2015. The clinical manifestations, biochemical tests, immunological function, molecular features, treatment, and follow-up of the patient were analyzed. The Chinese and PUBMED databases were searched with the key words "NFκB2" and "immune deficiency" and related literatures were reviewed.@*Results@#The patient had 4 episodes of pneumonias and one otitis media since the age of 6 months. The serum immunoglobulin levels were IgG 2.73 g/L, IgA<0.07 g/L, and IgM 0.12 g/L. The percentage of peripheral lymphocyte subsets demonstrated increased CD3+T lymphocyte (81.8%), increased CD4+ naïve T cell (39.1%), normal B cell (14.1%), low switched memory B and plasmablast B (respectively 0.1% and 0), and lightly diminished natural killer(NK) cell (4.13%). Within the peripheral CD4+T cells, the percentage of regulatory T cells (1.49% (control 4.08%)), T follicular helper (3.66% (control 11.0%)), and T helper 17 (9.65% (control 15.7%)) were decreased, while the percentage of T helper 2 (60.9% (control 46.5%)) was elevated. T lymphocyte proliferative response and T cell receptor repertoire diversity were normal. NK-cell cytotoxic activity was impaired. The whole-exome sequencing harbored a de novo heterozygous nonsense mutation in exon 22 (c.2557C>T; p. Arg853X) in the C-terminus of NF-κB2. The western blotting confirmed the decreased expression of NF-κB2 (p52) protein. The patient received intravenous immunoglobulin infusion monthly (400-600 mg/kg), followed by improvement of pulmonary infection. After searching the databases, a total of 28 cases (1 Chinese and 27 non-Chinese) were identified. There were 12 cases of nonsense mutation (5 were gain-of-function mutation), and 8 cases of missense and frameshift mutations, respectively. The main clinical manifestation was respiratory infection, followed by autoimmune diseases such as alopecia and trachyonychia. Fifteen cases developed adrenocorticotrophic hormone (ACTH) deficiency.@*Conclusions@#NF-κB2 signaling pathway played an important role in T and B lymphocyte differentiation, and NK-cell cytotoxic activity. NFκB2 mutation should be considered in cases with recurrent infections, hypogammaglobulinemia, and decreased memory B cells and plasma cells, especially when combined with ACTH deficiency.

Diagnosis and treatment progress of acquired immunologic deficiency syndrome-related lymphoma / 白血病·淋巴瘤

Malignancy is one of the most important complications of acquired immunodeficiency syndrome (AIDS) caused by human immunodeficiency virus (HIV) infection and destruction of host CD4-positive T lymphocytes. Lymphoma ranks first in AIDS-related malignancies. The clinical features of lymphoma patients infected with HIV are different from non-HIV infected patients. The host immune condition in anti-lymphoma chemotherapy also needs to be considered. This paper reviews the clinical characteristics of AIDS-related lymphoma and the attention in anti-lymphoma therapy according to the latest international research findings and related guidelines.

Short stature, optic nerve atrophy and Pelger-Huët anomaly syndrome with antibody immunodeficiency and aplastic anemia: a case report and literature review / 中华儿科杂志

Objective@#To investigate the clinical features and genetic characteristics of cases with NBAS gene defects.@*Method@#Characteristics of clinical materials, immunological data and gene mutation of the first case in China with NBAS gene mutation were retrospectively analyzed. The related literature was searched by using search terms'NBAS’.@*Result@#A 2-year-four-month old girl, was admitted due to 'fever and pallor for one day’. There was an intrauterine growth retardation at her fetal stage. Since her birth, she had suffered from recurrent infections and development delay was accompanied by persistent liver dysfunction. Her head circumference and height were 43.5 cm and 60 cm, respectively. She seemed pale. She had progeroid appearance with loose skin, sparse hair, proptosis and low-set ears. The cranial suture did no close and the anterior fontanel was about 6 cm×5 cm. Abdominal palpation showed that the liver was 2 cm below the right costal margin, and the spleen was 1.5 cm below the left rib. Both alanine aminotransferase(100-1 991 IU/L) and aspartate aminotransferase (191-1 367 IU/L) were persistently abnormal. Visual evoked potentials and fundus examination revealed optic nerve atrophy. Bone mineral density assessment showed osteoporosis. The IgG level was 2.0 g/L (3.41-19.6) and absolute count of CD19+B cells was 231.27/μl (608.8-2 167.7) . Her hemoglobin level was 53 g/L. Bone marrow smear showed serious hypoplasia in erythroid cell. The gene sequencing results showed NBAS gene c.5741C> T, pR1914H and c.6496-6497insA, p.S2166Ffs* 2 compound heterozygous mutations. A total of 8 literatures were collected including 57 cases with NBAS gene homozygous or compound heterozygous mutation. These 57 cases were characterized by short stature(88%, 50/57) , Pelger-Huët anomaly (75%, 43/57) , skeletal dysplasia (74%, 42/57), optic nerve atrophy (72%, 41/57), abnormality of liver enzymes or acute liver failure (42%,24/57), abnormalities of immune system(19%, 11/57), development delay of mental, language or sports(11%, 6/57). Other clinical manifestations such as progeroid appearance, proptosis and hypotonia were also common. NBAS gene c.5741G>A homozygous mutation accounted for 61% (35/57) cases.@*Conclusion@#Cases with NBAS gene defects often manifests as short stature, optic nerve atrophy, Pelger-Huët anomaly, skeletal dysplasia, recurrent infections, abnormality of liver enzymes, progeroid appearance, proptosis, hypotonia and immunodeficiency. Gene sequencing analysis showed NBAS gene homozygous or compound heterozygous mutations, and homozygous mutation of c.5741G>A was most common.

Pulmonary Complications in Primary Immunodeficiency Diseases / 소아알레르기및호흡기학회지

PURPOSE:Primary immunodeficiency diseases are disorders in which part of the body's immune system is missing or does not function properly due to intrinsic defects in the immune system. These patients have an increased susceptibility to pulmonary complications as well as primary infections. This study was to investigate pulmonary complications in patients with primary immunodeficiency diseases and characterize their patterns according to specific immune defects. METHODS:We retrospectively reviewed the medical records of 37 different cases of primary immunodeficiency diseases that were admitted to Severance hospital in Seoul between 1990 and 2006. RESULTS:Many patients had a previous history of recurrent respiratory infections and some suffered from pulmonary complications. Eight patients with hypogammaglobulinemia showed peribronchial wall thickening or bronchiectasis, and pneumatoceles or emphysematous changes were characteristic complications in two patients with hyper IgE syndrome. On microbiological examination, various bacteria, including Staphylococcus aureus, Pseudomonas aeroginosa, Streptococcus pneumoniae, were isolated from the hypogammaglobulinemia patients' sputum or ear discharge. In some patients with cell-mediated immune defects, such as chronic granulomatous disease or severe combined immune deficiency, yeast and ameba were isolated from the sputum and bronchial washing fluid respectively. CONCLUSION:Infections account for most of these complications, but the host reaction to infection seems to cause characteristic findings that could be helpful for diagnosis. The physician should be alert for the early diagnosis of children with primary immunodeficiency in order to prevent pulmonary complications.

Pulmonary Complications in Primary Immunodeficiency Diseases / 소아알레르기및호흡기학회지

PURPOSE:Primary immunodeficiency diseases are disorders in which part of the body's immune system is missing or does not function properly due to intrinsic defects in the immune system. These patients have an increased susceptibility to pulmonary complications as well as primary infections. This study was to investigate pulmonary complications in patients with primary immunodeficiency diseases and characterize their patterns according to specific immune defects. METHODS:We retrospectively reviewed the medical records of 37 different cases of primary immunodeficiency diseases that were admitted to Severance hospital in Seoul between 1990 and 2006. RESULTS:Many patients had a previous history of recurrent respiratory infections and some suffered from pulmonary complications. Eight patients with hypogammaglobulinemia showed peribronchial wall thickening or bronchiectasis, and pneumatoceles or emphysematous changes were characteristic complications in two patients with hyper IgE syndrome. On microbiological examination, various bacteria, including Staphylococcus aureus, Pseudomonas aeroginosa, Streptococcus pneumoniae, were isolated from the hypogammaglobulinemia patients' sputum or ear discharge. In some patients with cell-mediated immune defects, such as chronic granulomatous disease or severe combined immune deficiency, yeast and ameba were isolated from the sputum and bronchial washing fluid respectively. CONCLUSION:Infections account for most of these complications, but the host reaction to infection seems to cause characteristic findings that could be helpful for diagnosis. The physician should be alert for the early diagnosis of children with primary immunodeficiency in order to prevent pulmonary complications.