Primary immunodeficiency disease: a retrospective study of 112 Chinese children in a single tertiary care center.

BACKGROUND: Primary immunodeficiency disease (PID) is a disorder caused by an inherited flaw in the immune system that increases the susceptibility to infections. METHODS: In this study, 112 children with PID were diagnosed and classified based on the 2017 criteria presented by the International Union of Immunological Societies (IUIC) in a single tertiary care center from January 2013 to November 2018. We retrospectively studied the clinical features of those PID children and followed-up them as well. RESULTS: It was revealed that male/female ratio was 6:1. The most frequent diagnosed PID was severe combined immunodeficiency (SCID) (28.6%) and hyper-IgM (HIGM) syndrome (24.1%), followed by predominantly antibody deficiencies (17.8%). Combined immunodeficiencies with associated or syndromic features (12.5%) and congenital defects of phagocyte number, function, or both (10.7%) were less common in our center compared with SCID and HIGM syndrome. Besides, we found that 20 children (17.8%) had a positive family history of PID, and almost all cases (97.3%) had a history of recurrent infection. Recurrent respiratory tract infection was among the most common symptoms, followed by the bacterial infection of the skin and mucous membranes and diarrhea. Additionally, adverse event following immunization (AEFI) was found in 20.5% of the patients, and immune disorder was commonly observed in PID patients. In the present study, 47 patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), and 2-year overall survival (OS) rate for these patients was 78.7% (37/47). It is noteworthy that OS widely differed among PID patients with different phenotypes who underwent allo-HSCT. The 2-year OS rate for SCID, HIGM syndrome, and the remaining of PID patients who underwent allo-HSCT was 14.3, 83.3, and 100%, respectively. CONCLUSIONS: PID typically emerges at early age. Recurrent infection and serious infection were the most common clinical manifestations. Allo-HSCT is a relatively effective therapeutic strategy for PID patients.

Morbidity and mortality of Iranian patients with hyper IgM syndrome: a clinical analysis.

BACKGROUND: Defects in B cell class switch recombination (CSR) are a heterogeneous and yet very uncommon group of disorders which all have a genetic basis uniformly leading to hyper IgM (HIgM) syndrome. Due to the rare frequency of these conditions, a very small number of case series have been conducted on the affected patients. OBJECTIVE: To shed some light on the morbidity and mortality regarding a relatively large cohort of diagnosed CSR defective Iranian patients. METHODS: This study was performed using demographic information, laboratory findings and clinical data obtained from an observation of 33 Iranian patients of different ethnicities referred from all medical centers of Iran to the Children's Medical Center Hospital, pediatrics center of excellence, Tehran, Iran; of which 28 were males and 5 were females. RESULTS: Our patients mean age at the onset of symptoms was 1.8 ± 0.2 years; they were diagnosed with a mean delay of 4.4 ± 3.3 years and followed for a mean time of 5.7 ± 4.8 years. The most prominent clinical features observed were multi-organ infections, affecting mostly the respiratory system, followed by lymphoproliferative and autoimmune disorders, the latter being of much higher frequency (44%) in our study than the reported frequency in previous reports. The three year survival rate for our enrolled patients was 67.9%. CONCLUSIONS: Based on our findings, the most common cause of death in HIgM patients is respiratory failure. The molecular mechanism behind the nature of the CSR defective patients in Iran is more compatible with autosomal recessive mutations rather than X-linked HIgM syndrome which is in contrast with other large cohorts of patients with CSR defect.

First report of the Hyper-IgM syndrome Registry of the Latin American Society for Immunodeficiencies: novel mutations, unique infections, and outcomes.

Hyper-IgM (HIGM) syndrome is a heterogeneous group of disorders characterized by normal or elevated serum IgM levels associated with absent or decreased IgG, IgA and IgE. Here we summarize data from the HIGM syndrome Registry of the Latin American Society for Immunodeficiencies (LASID). Of the 58 patients from 51 families reported to the registry with the clinical phenotype of HIGM syndrome, molecular defects were identified in 37 patients thus far. We retrospectively analyzed the clinical, immunological and molecular data from these 37 patients. CD40 ligand (CD40L) deficiency was found in 35 patients from 25 families and activation-induced cytidine deaminase (AID) deficiency in 2 unrelated patients. Five previously unreported mutations were identified in the CD40L gene (CD40LG). Respiratory tract infections, mainly pneumonia, were the most frequent clinical manifestation. Previously undescribed fungal and opportunistic infections were observed in CD40L-deficient patients but not in the two patients with AID deficiency. These include the first cases of pneumonia caused by Mycoplasma pneumoniae, Serratia marcescens or Aspergillus sp. and diarrhea caused by Microsporidium sp. or Isospora belli. Except for four CD40L-deficient patients who died from complications of presumptive central nervous system infections or sepsis, all patients reported in this study are alive. Four CD40L-deficient patients underwent successful bone marrow transplantation. This report characterizes the clinical and genetic spectrum of HIGM syndrome in Latin America and expands the understanding of the genotype and phenotype of this syndrome in tropical areas.

A novel activation-induced cytidine deaminase (AID) mutation in Brazilian patients with hyper-IgM type 2 syndrome.

Activation-induced cytidine deaminase (AID) is a DNA editing protein that plays an essential role in three major events of immunoglobulin (Ig) diversification: somatic hypermutation, class switch recombination and Ig gene conversion. Mutations in the AID gene (AICDA) have been found in patients with autosomal recessive Hyper-IgM (HIGM) syndrome type 2. Here, two 9- and 14-year-old Brazilian sisters, from a consanguineous family, were diagnosed with HIGM2 syndrome. Sequencing analysis of the exons from AICDA revealed that both patients are homozygous for a single C to G transversion in the third position of codon 15, which replaces a conserved Phenylalanine with a Leucine. To our knowledge, this is a new AICDA mutation found in HIGM2 patients. Functional studies confirm that the homologous murine mutation leads to a dysfunctional protein with diminished intrinsic cytidine deaminase activity and is unable to rescue CSR when introduced in Aicda(-/-)stimulated murine B cells. We briefly discuss the relevance of AICDA mutations found in patients for the biology of this molecule.

Protective effect of IgM against colonization of the respiratory tract by nontypeable Haemophilus influenzae in patients with hypogammaglobulinemia.

BACKGROUND: Primary immunoglobulin deficiencies lead to recurrent bacterial infections of the respiratory tract and bronchiectasis, even with adequate immunoglobulin replacement therapy. It is not known whether patients able to secrete IgM (eg, those with hyper-IgM [HIgM] syndrome) are as susceptible to these infections as patients who lack IgM production (eg, those with panhypogammaglobulinemia [PHG]). OBJECTIVE: This study is aimed at identifying specific microbiological and clinical (infections) characteristics that distinguish immunoglobulin-substituted patients with PHG from patients with HIgM syndrome. METHODS: A cohort of patients with HIgM syndrome (n = 25) and a cohort of patients with PHG (n = 86) were monitored prospectively for 2 years while receiving similar polyvalent immunoglobulin replacement therapies. Regular bacterial analyses of nasal swabs and sputum were performed, and clinical events were recorded. In parallel, serum and saliva IgM antibody concentrations were measured. RESULTS: When compared with patients with PHG, patients with HIgM syndrome were found to have a significantly lower risk of nontypeable Haemophilus influenzae carriage in particular (relative risk, 0.39; 95% CI, 0.21-0.63). Moreover, patients with HIgM syndrome (including those unable to generate somatic hypermutations of immunoglobulin genes) displayed anti-nontypeable H influenzae IgM antibodies in their serum and saliva. Also, patients with HIgM syndrome had a lower incidence of acute respiratory tract infections. CONCLUSIONS: IgM antibodies appear to be microbiologically and clinically protective and might thus attenuate the infectious consequences of a lack of production of other immunoglobulin isotypes in patients with HIgM syndrome. Polyvalent IgG replacement therapy might not fully compensate for IgM deficiency. It might thus be worth adapting long-term antimicrobial prophylactic regimens according to the underlying B-cell immunodeficiency phenotype.

Immunoglobulin G subclass deficiency is the major phenotype of primary immunodeficiency in a Korean adult cohort.

Primary immunodeficiency disease (PID) is a rare disorder in adults. Most often, serious forms are detected during infancy or childhood. However, mild forms of PID may not be diagnosed until later in life, and some types of humoral immunodeficiency may occur in adulthood. The purpose of this study was to identify clinical features of PID in Korean adults. A retrospective study was performed on 55 adult patients who were diagnosed as PID between January 1998 and January 2009 at a single tertiary medical center in Korea. IgG subclass deficiency was the most common phenotype (67%, 37/55), followed by total IgG deficiency (20%, 11/55), IgM deficiency (7%, 4/55), common variable immunodeficiency (2%, 1/55), and X-linked agammaglobulinemia (2%, 1/55). IgG3 and IgG4 were the most affected subclasses. Upper and lower respiratory tract infections (76%) were the most frequently observed symptoms, followed by multiple site infection (11%), urinary tract infection, and colitis. Bronchial asthma, rhinitis, and several autoimmune diseases were common associated diseases. IgG and IgG subclass deficiency should be considered in adult patients presenting with recurrent upper and lower respiratory infections, particularly in those with respiratory allergies or autoimmune diseases.

Infección por el virus de la inmunodeficiencia humana de tipo 2 (VIH-2) y los virus linfotrópico humano de células T de tipos 1 y 2 (HTLV-1/2) en España / No disponible

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Spectrum of primary immune deficiency at a tertiary care hospital.

OBJECTIVE: To report various primary immune deficiencies diagnosed in children at a tertiary care hospital, their clinical manifestations and laboratory profile. METHODS: Case records of children diagnosed to have primary immunodeficiency disorders over a period of 24 months at a tertiary care hospital in northern India were evaluated. RESULTS: Twenty-seven children (M: F=3.5: 1) with mean age of 5.4 +/- 4.6 yrs (2 mo-16 yr) were diagnosed to have primary immunodeficiency. Thirteen children had chronic granulomatous disease (CGD), 4 had severe combined immunodeficiency (SCID), 4 had hypogammaglobulinemia, 2 had Ataxia telangiectasia, and one each had DiGeorge syndrome, Wiskott Aldrich syndrome, hyper IgM syndrome and leukocyte adhesion defect. Common mode of presentation were recurrent/ persistent pneumonia in 19, recurrent/ persistent diarrhea in 10, deep seated abscesses in 8, allergy in 3, disseminated tuberculosis infection in 2, extensive fungal infections in 2 and 1 each of disseminated cytomegalovirus (CMV) infection, disseminated BCG disease, otitis media and meningitis. Family history of sibling deaths was elicited in 2 families. Infectious agents were isolated in 16 cases. CONCLUSION: From a single center 27 patients with primary immune deficiency could be identified by chart review, suggesting need for high index of suspicion for diagnosis of primary immune deficiency in India. Though the exact prevalence is not known there is need to make a registry to document the magnitude of problem of these disorders.