Transient Hypogammaglobulinemia Of Infancy Research Articles

Clinical and experimental treatment of primary humoral immunodeficiencies.

Selective IgA deficiency (sIgAD), common variable immunodeficiency (CVID), and transient hypogammaglobulinemia of infancy (THI) are the most frequent forms of primary antibody deficiencies. Difficulties in initial diagnosis, especially in the early childhood, the familiar occurrence of these diseases, as well as the possibility of progression to each other suggest common cellular and molecular patomechanism and a similar genetic background. In this review, we discuss both similarities and differences of these three humoral immunodeficiencies, focusing on current and novel therapeutic approaches. We summarize immunoglobulin substitution, antibiotic prophylaxis, treatment of autoimmune diseases, and other common complications, i.e. cytopenias, gastrointestinal complications, and granulomatous disease. We discuss novel therapeutic approaches such as allogenic stem cell transplantation and therapies targeting-specific proteins, dependent on the patient's genetic defect. The diversity of possible therapeutics models results from a great heterogeneity of the disease variants, implying the need of personalized medicine approach as a future of primary humoral immunodeficiencies treatment.

Transient hypogammaglobulinemia of infancy and unclassified syndromic immunodeficiencies are highly common in oesophageal atresia patients

AbstractDue to the high rate of post‐operative sepsis and other infectious complications, a routine immunological screening protocol has been initiated since 2015 in our paediatric surgery clinic for all patients admitted with oesophageal atresia (EA) and warrant a delayed definitive treatment. In our study, we aimed to evaluate the immunodeficiencies in EA patients, by comparing them to healthy age‐matched controls. As a prospective cohort study, EA patients admitted between 2015 and 2022, who had their definitive operation after the newborn period (>28 days of age) were included. On admission, serum concentrations of IgG, IgA, IgM, lymphocyte subset levels, C3 and C4 levels, specific IgG antibody responses against hepatitis B, hepatitis A, measles, varicella zoster were evaluated. The patients were age‐matched with healthy controls to compare the results and followed up until three years of age. If a humoral immunodeficiency was detected, intravenous immunoglobulin treatment was administered before major oesophageal surgery and during follow‐up. 31 EA patients (18 M/13F) with a mean age of 13.3 ± 9.0 months were compared with 40 age‐matched healthy controls. Mean serum IgG levels were found to be statistically lower than controls in all age groups (P < .05). Transient hypogammaglobulinemia of infancy (THI) and unclassified syndromic immunodeficiencies (USI) were found to be strikingly high, accounting for 29.0% and 22.5%, respectively, adding up to 51.5% of EA patients. This is the first study evaluating immunodeficiencies in EA patients found in the reviewed literature. More than half of EA patients that required delayed surgery had humoral immunodeficiency, so preoperative screening and immunology referral may improve patient outcomes.

Transcriptome profiling of regulatory T cells from children with transient hypogammaglobulinemia of infancy.

Transient hypogammaglobulinemia of infancy (THI) is one of the most common forms of hypogammaglobulinemia in the early childhood. THI is usually associated with chronic, recurrent bacterial and viral infections, life-threatening in some cases, yet its pathogenesis is still largely unknown. As our previous findings indicated the possible role of Treg cells in the pathomechanism of THI, the aim of the current study was to investigate gene expression profile of Treg cells isolated from THI patients. The transcriptome-wide gene profiling was performed using microarray technology on THI patients in two time-points: during (THI-1), and in resolution phase (THI-2) of hypogammaglobulinemia. As a result, a total of 1086 genes were differentially expressed in THI-1 patients, when compared to THI-2 as well as control group. Among them, 931 were up- and 155 downregulated, and part of them encodes genes important for Treg lymphocyte biology and function, i.e. transcription factors/cofactors that regulate FOXP3 expression. Thus, we postulate that Treg cells isolated from THI patients during hypogammaglobulinemia display enhanced suppressor transcriptome signature. Treg expression profile of THI children after normalization of Ig levels largely resembles the results obtained in healthy control group, suggesting THI Treg transcriptome seems to return to that observed in healthy children. Taken together, we suggest that THI pathomechanism is associated not only with transiently elevated Treg cell numbers, but also with their enhanced regulatory/inhibitory functions. These findings expand our knowledge of human Treg cells and may be useful for the future diagnosis or management of THI.

Hypogammaglobulinemia in neonates: illustrative cases and review of the literature.

This article presents a review of causes of hypogammaglobulinemia in neonates utilizing illustrative cases to demonstrate commonly seen conditions. Overall, the causes of low immunoglobulin level can be divided into three main categories: decreased maternal transfer or production (due to physiological nadir, transient hypogammaglobulinemia of infancy, medication effects, or immunodeficiency), increased loss of immunoglobulins (from the gastrointestinal (GI) system, lymphatics, kidneys, skin disease, or blood loss) or destruction/suppression (from medication effects). Treatment of hypogammaglobulinemia is generally tailored to the underlying cause and condition of the patient. This can be through supportive care, prophylactic measures, or with immunoglobulin G (IgG) replacement at the recommendation of an immunologist.

A Systematic Review of the Clinical Diagnosis of Transient Hypogammaglobulinemia of Infancy.

Transient hypogammaglobulinemia of infancy (THI) is a primary immunodeficiency caused by a temporary decline in serum immunoglobulin G (IgG) levels greater than two standard deviations below the mean age-specific reference values in infants between 5 and 24 months of age. Preterm infants are particularly susceptible to THI, as IgG is only transferred across the placenta from mother to infant during the third trimester of pregnancy. This study aimed to conduct a systematic review of the diagnostic criteria for transient hypogammaglobulinemia of infancy. Systematic review: Three electronic databases (PubMed, MEDLINE, and Google Scholar) were manually searched from September 2021 to April 2022. Abstracts were screened to assess their fit to the inclusion criteria. Data were extracted from the selected studies using an adapted extraction tool (Cochrane). The studies were then assessed for bias using an assessment tool adapted from Cochrane. Of the 215 identified articles, 16 were eligible for examining the diagnostic criteria of THI. These studies were also assessed for bias in the six domains. A total of five studies (31%) had a low risk of bias, while four studies (25%) had a high risk of bias, and bias in the case of seven studies (44%) was unclear. We conclude that THI is only definitively diagnosed after abnormal IgG levels normalise. Hence, THI is not a benign condition, and monitoring for subsequent recurrent infections must be conducted. The diagnostic criteria should also include vaccine and isohaemagglutinin responses to differentiate THI from other immunological disorders in infants.

Kawasaki Disease and Inborn Errors of Immunity: Exploring the Link and Implications

The exact etiopathogenesis of Kawasaki disease (KD), the most common childhood vasculitis, remains unknown; however, an aberrant immune response, possibly triggered by an infectious or environmental agent in genetically predisposed children, is believed to be the underlying pathogenetic mechanism. Patients with inborn errors of immunity (IEI) are predisposed to infections that trigger immune dysregulation due to an imbalance in various arms of the immune system. KD may develop as a complication in both primary and secondary immunodeficiencies. KD may occur either at disease presentation or have a later onset in IEIs. These include X-linked agammaglobulinemia (XLA), selective IgA deficiency, transient hypogammaglobulinemia of infancy; Wiskott–Aldrich syndrome (WAS), hyper IgE syndrome (HIES); chronic granulomatous disease (CGD), innate and intrinsic immunity defects, and autoinflammatory diseases, including PFAPA. Hitherto, the association between KD and IEI is confined to specific case reports and case series and, thus, requires extensive research for a comprehensive understanding of the underlying pathophysiological mechanisms. IEIs may serve as excellent disease models that would open new insights into the disease pathogenesis of children affected with KD. The current review highlights this critical association between KD and IEI supported by published literature.

A Case Report and Review of Increased IgE in Patients with Transient Hypogammaglobulinemia of Infancy and Atopic Dermatitis after Normalization of IgG

The coexistence of a high IgE level and transient hypogammaglobulinemia of infancy ( THI ) with atopic dermatitis (AD) is well known, but the coexistence with a marked serum IgE level ≥ 1000 IU/mL is a rare finding. Literature is scarce regarding IgE levels in patients with THI and AD after treatment with immunoglobulin (Ig). We reported a female infant 8 months old, with THI and severe AD. She was treated with intravenous immunoglobulin (IVIG) infusion after the failure of conventional therapy. Initially, serum levels of IgE were high, and serum levels of IgG were low. After 4 weeks of treatment with IVIG, patient profile showed normalization of IGE and higher elevation in IgG level. The present article is the first to describe a finding of marked IgE elevation (> 1000 IU/mL) after treatment with IVIG. Furthermore, our finding is supported by our review of increased IgE levels in patients with THI and AD who received IG therapy. According to our review different trend of IgE levels in patients who achieved spontaneous normalization of IgG was found.

Regulatory T and B cells in transient hypogammaglobulinemia of infancy.

Transient hypogammaglobulinemia of infancy (THI) is a heterogeneous disorder caused by an abnormal delay in reaching normal IgG levels in the first three years of life. Although THI is a common primary immune deficiency, its pathogenesis has not been fully elucidated. We aimed to investigate the role of regulatory T cells (Tregs) and B cells (Bregs) in the pathogenesis of THI. T and B cell subsets were evaluated in 40 patients with THI aged 6-41 months and 23 healthy controls aged 6-51 months using flow cytometry. CD4 and interleukin-2 receptor-α alpha (CD25) expression and a lack of interleukin-7 receptor-α (CD127) were used for Treg identification. FoxP3 expression in Tregs was determined as a percentage and mean fluorescence intensity. B cell subsets (plasmablast, mature naive, primarily memory, new memory) and Bregs were defined according to CD19, CD38, and CD24 expressions. Patients with THI (15 females and 25 males; mean age: 18.8 ± 8.6 months) and controls (10 females and 13 males; mean age: 22.6 ± 13.1 months) participated in this study. While the proportion of Tregs of children with THI were significantly increased compared to the controls, primarily memory B cells were reduced. Additionally, the proportions of CD127 in CD3+ and CD3+CD4+ T cells were significantly reduced in the patients with THI compared to the control. No significant difference was detected in the FoxP3 expression of Tregs and the frequency of Bregs in the children with THI. Increased Tregs and decreased primarily memory B cells may cause antibody production delay in children with THI. Changes in the T and B cell compartments may be related to chronic immune activation and affected cellular immunity in THI. Further studies are needed to use T and B cell subsets in the prediction of IgG level recovery.

One-year intravenous immunoglobulin replacement therapy: efficacy in reducing hospital admissions in pediatric patients with Inborn Errors of Immunity

ObjectivesTo compare the frequency of hospitalization in children with Inborn Errors of Immunity with antibody deficiency previous to intravenous immunoglobulin (pre- IVIG) with a one-year period after initial IVIG (post-IVIG). MethodsMedical reports of 45 patients during an eight-year period were reviewed from 2018 to 2019. Wilcoxon-test was used for related samples. ResultsForty-five children were included in the study, aged 29–249 months of age, and most of them (64.4%) were males. Median ages at onset symptoms and at diagnosis were 6 and 73 months old, respectively. Specific antibody deficiency and unclassified hypogammaglobulinemia were the predominant diagnoses (31.1% and 17.8%, respectively). X-linked agammaglobulinemia, Hyper IgE syndrome, Hyper IgM, transient hypogammaglobulinemia of infancy, and Common Variable Immunodeficiency (CVID) were also reported, in a low frequency. Forty-four (97.8%) patients were hospitalized before IVIG, and 10 patients (22.2%) after. Annual mean hospital admission reduced from 2.5 to 0.5, pre and post-IVIG, respectively (p < 0.0001). Mean length of stay (LOS) reduced from 71 to 4.7 days/year (p < 0.0001) in general ward and in the PICU from 17.2 days/year to zero (p < 0.0002). Pneumonia was the main cause of hospital admission with a reduction in the number of episodes per patient from an average of 2.2–0.1 per year (p < 0.001). Concomitant use of antibiotic prophylaxis did not influence the number of hospital admission. ConclusionOne-year intravenous IVIG significantly decreased the number of hospitalizations and length of stay in children with impaired antibody production. Social and economic impacts would be required.

Vaccination in PADs.

Primary antibody deficiencies (PADs) are the most common primary immunodeficiencies (PIDs). They can be divided into the following groups, depending on their immunological features: agammaglobulinemia; common variable immunodeficiency (CVID) isotype; hyper IgM isotype; light chain or functional deficiencies with normal B cell count; specific antibody deficiency with normal Ig concentrations and normal numbers of B cells and transient hypogammaglobulinemia of infancy. The role of vaccination in PADs is recognized as therapeutic, diagnostic and prognostic and may be used in patients with residual B-cell function to provide humoral immunity to specific infective agents. According to their content and mechanisms, vaccines are grouped as live attenuated, inactivated (conjugated, polysaccharide), mRNA or replication-deficient vector vaccines. Vaccination may be unsafe or less effective when using certain vaccines and in specific types of immunodeficiency. Inactivated vaccines can be administered in PAD patients even if they could not generate a protective response; live attenuated vaccines are not recommended in major antibody deficiencies. From December 2020, European Medicines Agency (EMA) approved vaccines against COVID-19 infection: according to ESID advises, those vaccinations are recommended in patients with PADs. No specific data are available on safety and efficacy in PAD patients.

To What Extent do Transient Hypogammaglobulinemia of the Infancy and Allergic Diseases Coexist?

Objective: To investigate the clinical features and follow-up results of the patients with transient hypogammaglobulinemia of infancy (THI) and to understand to what extent the condition coexists with allergic diseases. Materials and Methods: Between January 2010 and February 2019, 172 patients who had been referred to Ankara University Faculty of Medicine’s Pediatric Immunology and Allergy Outpatient Department for findings of atopic disease or for frequent infections with a suspicion of PID, who were diagnosed with THI, and followed-up for at least one year were included in this study. Their clinical and immunological features and follow-up results were evaluated retrospectively. Results: Of the 172 patients, 59% were boys. Median time of symptom onset was 14 months (1-46 months), median time of admission was 20 months (6-30 months), and consanguineous marriages were seen in 20% of the families. The most common referral complaints were respiratory tract infections and non-wheezing allergic diseases with rates of 71.5% and 27%, respectively. Cellular immune system analyses were normal. During a median follow-up time of 36 months, 42% of the patients recovered, 25% (n=43) still had THI, 25% (n=43) had unclassified hypogammaglobulinemia (UCG), 4% (n=7) had partial IgA deficiency, and 4% (n=7) had partial IgM deficiency. Allergic diseases were seen in 46% of the patients. An asthma diagnosis was made in 35.4% of the patients, allergic rhinitis in 5% and atopic dermatitis in 12.7%. The skin prick test was positive in 15% of them. Conclusion: THI mostly improves spontaneously in time. However, hypogammaglobulinemia can last until later years in life in a group of patients. Allergic diseases increase with the presence of THI. In patients who are admitted with allergic disease symptoms, underlying hypogammaglobulinemia should also be investigated.

Diagnostic approach of hypogammaglobulinemia in infancy.

Primary B-cell immunodeficiency is the most frequent immune defect in infancy. Selective absence of serum and secretory immunoglobulin IgA is the most common, with rates ranging from 1/333 persons to 1/16000, among different races. By contrast, it has been estimated that hypo/agammaglobulinemia occurs with a frequency of 1/50000 persons. Patients with antibody deficiency are usually recognized because they have recurrent infections with encapsulated bacteria or a history of failure to respond adequately to antibiotic treatment. However, some individuals, mainly those affected by IgA deficiency (SIgAD) or transient hypogammaglobulinemia of infancy , may have few or no infections.

Transient hypogammaglobulinaemia of infancy: many patients recover in adolescence and adulthood.

Transient hypogammaglobulinaemia of infancy (THI) is a relatively rare disorder where there is an exaggeration of the physiological nadir of immunoglobulin (Ig)G between loss of transplacentally acquired maternal IgG and production by the infant. Patients may be vulnerable to infections during the period of hypogammaglobulinaemia. The precise time to recovery in all infants is currently unknown. We sought to determine the clinical features and time-course of recovery for patients with THI. We reviewed our experience with THI over the last three decades in order to describe clinical and laboratory features, as well as the time-course of recovery. Forty-seven patients were identified with THI. Only thirty-seven per cent remitted by 4years of age, while some patients did not recover until the third or fourth decade. In keeping with previous studies, the majority (25 of 47) presented with recurrent infections, nine had a family history of immunodeficiency and 13 had adverse reactions to food as their dominant clinical manifestation. Chronic tonsillitis developed in 10patients and symptoms improved following surgery. The group with food allergies recovered sooner than those presenting with infections or with a family history immunodeficiency. Eight patients failed to respond to at least one routine childhood vaccine. Two have IgA deficiency and four individuals recovering in adolescence and adulthood continue to have borderline/low IgG levels. None have progressed to common variable immunodeficiency disorders (CVID). THI is a misnomer, as the majority do not recover in infancy. Recovery from THI can extend into adulthood. THI must be considered in the differential diagnosis of adolescents or young adults presenting with primary hypogammaglobulinemia.

Epidemiological and clinical features of patients with primary antibody deficiency disorders in the east of Turkey

Aim: To describe the demographic and clinical features of patients diagnosed with primary antibody deficiency Material and Methods: The medical records of pediatric patients who were diagnosed with primary antibody deficiency were reviewed. Patients were diagnosed with primary antibody deficiency based on the European Society for Immunodeficiencies diagnostic criteria. Result: A total of 60 patients with primary antibody deficiency were identified; 39 patients (65%) were male and median age was 5 (1-18) years of age, while median diagnosis age was 3 (6 mo-14 yr) years. Twenty-one patients (35%) were diagnosed with transient hypogammaglobulinemia of infancy, thirteen (21.7%) with selective Ig A deficiency, five (8.3%) with congenital agammaglobulinemia, five (8.3%) with selective Ig M deficiency, five (8.3%) with unclassified hypogammaglobulinemia, four (6.7%) with Ig G subclass deficiency, two (3.3%) with severe combined immune deficiency, two (3.3%) with common variable immunodeficiency, two (3.3%) with hyper Ig M syndrome, and one patient was diagnosed with pneumococcal vaccine responsiveness, respectively. Eleven patients (18.3%) had consanguinity and six patients (10%) had family history. The most common complaint was frequent respiratory tract infections. Four patients had dermatitis in addition to infection. Three patients had hematopoietic stem cell transplantation and 23 patients (38.3%) received intravenous immunoglobulin treatment. Two patients died during the follow up. Conclusion: Our results indicated that diagnosis is delayed and the patients who are diagnosed with primary antibody deficiency frequently have respiratory tract infections.

Transient hypogammaglobulinemia of infancy with no evidence of immunodeficiency other than atopic dermatitis: A case report and review of literature

Transient hypogammaglobulinemia of infancy with no evidence of immunodeficiency other than atopic dermatitis: A case report and review of literature

The Role of Hypogammaglobulinemia in Childhood Asthma

Background: The relationship between hypogammaglobulinemia and wheezing in childhood has been previously revealed. Objectives: The study aimed to investigate co-morbid immune deficiency in unresponsive asthmatic children, characterize the type of immune deficiency, and determine any possible effect of immune deficiency treatment on the applied standard guideline of asthma treatment. Methods: This was a prospective study conducted between January 2012 and December 2014. A total of 286 children whose serum immunoglobulin (Ig) levels had been analyzed were collected. Among those children, 125 (m/f = 79:46, mean +-SD of age = 41.3 + 25.2 months) were enrolled as they had uncontrolled moderate to persistent asthma. Those 125 children were categorized as the only asthma group and the asthma + hypogammaglobulinemia (HGG) group depending on their immunoglobulin concentrations. Results: Seventy-six of the 125 children (60.8%) had co-morbid hypogammaglobulinemia. Atopy was higher in the Asthma + HGG group (P = 0.044). The most frequent co-morbid HGG was transient hypogammaglobulinemia of infancy (THGI) (46.1%) and IgG subclass deficiency (32.9%). Although the comparison of the percentage use of the inhaled corticosteroids (ICSs) showed no significant difference between the two groups at the initial evaluation, the dose of ICS significantly decreased only in the asthma + HGG group (P = 0.017). Conclusions: The majority of asthmatic children having symptoms despite appropriate guideline-based treatment may have a co-morbid immunological abnormality. Presented data demonstrated the necessity of immunological evaluation of uncontrolled asthmatic children to prevent long-term side effects of high-dose ICS, reduce the frequency and severity of asthma symptoms, and improve the quality of life.

B lymphocyte subsets and outcomes in patients with an initial diagnosis of transient hypogammaglobulinemia of infancy.

Transient hypogammaglobulinemia of infancy (THI) is a common immunodeficiency, but definitive diagnosis can only be made retrospectively. While the pathogenesis is still unknown, abnormalities have been reported in the B cell compartment. In this study, we analysed the B cell subsets of patients with an initial THI diagnosis (n=20) and compared them with those of healthy age-matched Turkish children (n=72). Flow cytometric analyses of the B subsets were performed by stainingwith anti-CD27-PE, anti-CD19-PerCP, anti-IgD-FITC and anti-IgM-APC antibodies. During a median follow-up of 6.6years, 13 patients whose IgG levels had normalized before they reached four years of age were diagnosed with definitive THI. The memory subsets of these patients were lower but not statistically different from the healthy controls (HC). The remaining seven patients had prolonged hypogammaglobulinemia after the age of four and had significantly lower memory B cell subsets compared to the HC. On follow-up, these patients had not experienced recurrent infections or autoimmunity. Re-evaluation of patients' B cell subsets six years later showed that the memory B cell ratios had increased to levels comparable to HC, despite the patients still having mildly low IgG levels. Patients with prolonged hypogammaglobulinemia had lower levels of memory B cells despite having a similar clinical course to patients who had been diagnosed with definitive THI. This subgroup of putative THI patients poses a diagnostic and classification dilemma. Our results suggested that these patients' memory B cells and IgG levels may recover over time.

A Ten-Year Surveillance of 80 Children with Primary Immunodeficiencies

Background: Primary immunodeficiency disorders are a diverse group of rare genetic diseases that are often under-recognized. Therefore, significant morbidities and mortalities ensue due to diagnosis delay. This is an evaluation of clinical presentations and laboratory data of children referred to Mofid University Hospital during a 10-year period. The aim of this study is to provide epidemiologic data for early diagnosis and proper management of these patients. Methods: A total of 80 children referred to Mofid’s Children Hospital suspected to primary immunodeficiencies (PIDs) were evaluated clinically. The demographic, clinical, and laboratory data were collected in detail and were analyzed as a cross-sectional study. Missing data were completed in follow-up visits. Results: The prevalence of antibody deficiencies, phagocytic defects, and combined immunodeficiencies in 80 children with primary immunodeficiency syndromes were respectively 36.25%, 32.5%, and 31.25%. Common variable immunodeficiency (13.75%) and severe combined immunodeficiency (12.5%) had the highest prevalence among these disorders and the lowest prevalence were reported for cyclic neutropenia (5%), ataxia-telangiectasia (5%), and transient hypogammaglobulinemia of infancy (3.75%). The most common mode of inheritance detected was an autosomal recessive pattern. Pneumonia, otitis media, and diarrhea were the most common complications in the course of these disorders, which were seen respectively in 30%, 18.8%, and 15% of the patients. Conclusions: Issues regarding clinical presentation and management of primary immunodeficiencies continue to puzzle the clinical practitioner. Epidemiological data are needed to increase the awareness of the physicians regarding primary immunodeficiency disorders and to support the benefits of early diagnosis and treatment. Diagnosis delay is associated with increased morbidities and even mortalities.

The level of myeloid-derived suppressor cells positively correlates with regulatory T cells in the blood of children with transient hypogammaglobulinaemia of infancy.

IntroductionTransient hypogammaglobulinaemia of infancy (THI) is a primary immunodeficiency characterised by low levels of immunoglobulin G (often with concomitant decrease of IgA and sometimes also of IgM) with still unknown exact reason. A delayed normalisation of the immunoglobulin level in THI may be associated with a transiently elevated number of regulatory T cells (Treg). Although in cancer and chronic inflammation it was shown that the level of Treg cells can be increased by myeloid-derived suppressor cells (MDSCs), until now no studies have been performed in the context of the role of MDSCs in THI and their correlation with Treg cells. Consequently, we aimed to determine the occurrence of MDSCs in the peripheral blood of children with THI and correlate their level with the level of Treg cells.Material and methodsFlow cytometry analyses of Mo-MDSCs and Gr-MDSCs, characterised as HLA-DR–CD11b+CD15–CD14+ and HLA-DR–CD11b+CD15+CD14–, respectively, and Treg (CD4+CD25+Foxp3+) cells were performed.ResultsThe proportion of Mo-MDSCs and Gr-MDSCs was significantly higher in the group of THI patients with elevated level of Treg cells (from the 95% confidence interval level of healthy controls). The cells with Mo-MDSC and Gr-MDSC characteristics positively correlated with the level of Treg cells. Moreover, children with a higher proportion of circulating Treg cells, and thereby higher level of MDSCs, showed delayed normalisation of IgG level and recovery.ConclusionsThese findings show for the first time that MDSCs may be involved in the pathomechanism of THI, probably acting through the induction of Treg cells.

Surveillance of Primary Immunodeficiency Disorders in Mofid Children's Hospital: A 10-year retrospective experience

Background: Primary immunodeficiency disorders comprise a heterogeneous group of diseases in which there is a defect in the development or function of the immune system. Clinical presentation of these disorders is highly variable. The aim of this study was to determine the frequency and type of primary immunodeficiency disorders, diagnostic delay, common pathogenic microorganisms, and infectious complications in patients, admitted to Mofid Children’s hospital in the past decade (2004 - 2014). Methods: The data of patients with a diagnosis of primary immunodeficiency disorder, admitted to Mofid Children’s hospital from 2004 to 2014, were reviewed. The frequency, diagnostic delay, pathogenic microorganisms, and their sequelae were determined. Results: In 32 patients (20 males and 12 females) admitted to Mofid hospital in the past decade, chronic granulomatous disease was the most frequent primary immunodeficiency disorder (22%). Other immunodeficiency disorders in these patients included X-linked agammaglobulinemia, hyper IgM syndrome, common variable immunodeficiency, severe combined immunodeficiency, ataxia-telangiectasia syndrome, transient hypogammaglobulinemia of infancy, leukocyte adhesion deficiency, and Kostmann syndrome. The mean age at onset of these disorders was 15 months, and the mean delay in diagnosis was 20 months. Pneumonia was the most common infectious manifestation (53%), and Acinetobacter was the most common isolated microorganism. Conclusions: Diagnostic delay is a major concern in patients with primary immunodeficiency disorders. Ethnic and geographical differences may significantly influence the frequency and presentation of these disorders. Therefore, local epidemiological data are always necessary and useful in the management of primary immunodeficiency disorders.