Research

A child with X-linked agammaglobulinemia and Kawasaki disease: an unusual association.

Rheumatol Int. 2017 Apr 01;:

Authors: Sharma D, Guleria S, Suri D, Rawat A, Garg R, Singh S

Abstract
An association of X-linked agammaglobulinemia (XLA) with Kawasaki disease (KD) is very uncommon. Only two case reports are available so far in pediatric literature. Patients with XLA have recurrent infections and physical examination have absent lymph nodes and tonsils. Laboratory investigations reveal hypogammaglobulinemia and reduced or absent B cells on flow cytometry. KD is a medium vessel vasculitis. Here, we report a 12 year old boy with X-linked agammaglobulinemia on regular replacement intravenous immunoglobulin who developed KD on follow-up. This is an uncommon occurrence.

PMID: 28365793 [PubMed – as supplied by publisher]

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Chronic Granulomatous Disease in Patients Reaching Adulthood: A Nationwide Study in France.

Clin Infect Dis. 2017 Mar 15;64(6):767-775

Authors: Dunogué B, Pilmis B, Mahlaoui N, Elie C, Coignard-Biehler H, Amazzough K, Noël N, Salvator H, Catherinot E, Couderc LJ, Sokol H, Lanternier F, Fouyssac F, Bardet J, Bustamante J, Gougerot-Pocidalo MA, Barlogis V, Masseau A, Durieu I, Lecuit M, Suarez F, Fischer A, Blanche S, Hermine O, Lortholary O

Abstract
Background: Although prognosis of Chronic Granulomatous Disease (CGD) has greatly improved, few studies have focused on its long-term outcome. We studied the clinical course and sequelae of CGD patients diagnosed before age 16, at various adult time points.
Method: Cross-sectional French nationwide retrospective study of patients screened through the National Reference Center for Primary Immunodeficiencies (CEREDIH) registry.
Results: Eighty CGD patients (71 males [88.7%], 59 X-linked [73.7%], median age 23.9 years [minimum, 16.6; maximum, 59.9]) were included, Median ages at diagnosis and last follow-up were 2.52 and 23.9 years, respectively. Seven patients underwent hematopoietic stem cell transplantation. A total of 553 infections requiring hospitalization occurred in 2017 patient-years. The most common site of infection was pulmonary (31%). Aspergillus spp. (17%) and Staphylococcus aureus (10.7%) were the commonest pathogens. A total of 224 inflammatory episodes occurred in 71 patients, mainly digestive (50%). Their characteristics as well as their annual frequency did not vary before and after age 16. Main sequelae were a small adult height and weight and mild chronic restrictive respiratory failure. At age 16, only 53% of patients were in high school. After age 30 years, 9/13 patients were working. Ten patients died during adulthood.
Conclusions: Adult CGD patients displayed similar characteristics and rates of severe infections and inflammatory episodes that those of childhood. The high rate of handicap has become a matter of medical and social consideration. Careful follow-up in centers of expertise is strongly recommended and an extended indication of curative treatment by HSCT should be considered.

PMID: 28362954 [PubMed – in process]

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Vaccine Associated Paralytic Poliomyelitis Unmasking Common Variable Immunodeficiency.

Indian Pediatr. 2017 Mar 15;54(3):241-242

Authors: Gomber S, Arora V, Dewan P

Abstract
BACKGROUND: Oral polio vaccine can rarely lead to Vaccine-associated paralytic poliomyelitis (VAPP).
CASE CHARACTERISTICS: A 2-year-old child with asymmetric paralysis of lower limbs following first booster of oral polio vaccine; type 2 Vaccine-derived poliovirus (VDPV) isolated. Subsequently, the child was diagnosed to have common variable immunodeficiency.
OUTCOME: Paralysis gradually improved on follow-up; monthly intravenous immunoglobulin therapy started for primary immunodeficiency.
MESSAGE: We need to evaluate children with VAPP for underlying immunodeficiency.

PMID: 28361789 [PubMed – in process]

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Measurement of Health-Related Quality of Life in Primary Antibody-Deficient Patients.

Immunol Invest. 2017 Mar 30;:1-12

Authors: Ataeinia B, Montazeri A, Tavakol M, Azizi G, Kiaee F, Tavakolinia N, Negahdari B, Mohammadi J, Abolhassani H, Rezaei N, Aghamohammadi A

Abstract
BACKGROUND: Primary immunodeficiency diseases are a group of disorders that result from a variety of defects of the immune system. Primary antibody deficiencies (PADs) are the most common forms of these disorders. Occurrence of recurrent infections, autoimmune diseases, cancers, and lymphoproliferative disorders is higher in PAD patients. Chronicity of these diseases, delayed diagnosis, inadequate treatment, and treatment side effects may affect the quality of life (QoL) of PAD patients. Evaluating QoL is important for patient care, understanding the burden of these diseases, and finding the patients’ major health problems. We investigated the QoL in a group of PAD patients undergoing regular follow-up and treatment at the Children’s Medical Center Hospital in Tehran, Iran.
METHODS: Seventy patients with a diagnosis of PAD in two age groups (younger and older than 18 years) were included. QoL was measured using PedsQL and SF-36 questionnaires. Correlation of demographic, clinical, and immunological parameters with QoL scores was assessed and patients’ scores were compared with the normal population, using nonparametric tests of SPSS software.
RESULTS: Patients expressed significantly reduced scores in some mental and physical components. Patients with longer follow-up periods had higher scores in mental components but physical component scores were still low. There was no significant correlation between sex, age, and disease types with scores.
CONCLUSIONS: PAD patients had significantly lower scores in mental and physical components compared to normal population. By early diagnosis and long-term follow-up periods, we may be able to prevent complications and help patients to have a better QoL.

PMID: 28358233 [PubMed – as supplied by publisher]

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Preference of Genetic Diagnosis of CXCR4 Mutation Compared with Clinical Diagnosis of WHIM Syndrome.

J Clin Immunol. 2017 Mar 28;:

Authors: Aghamohammadi A, Abolhassani H, Puchalka J, Greif-Kohistani N, Zoghi S, Klein C, Rezaei N

PMID: 28353164 [PubMed – as supplied by publisher]

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Exome sequencing for simultaneous mutation screening in children with hemophagocytic lymphohistiocytosis.

Int J Hematol. 2017 Mar 28;:

Authors: Mukda E, Trachoo O, Pasomsub E, Tiyasirichokchai R, Iemwimangsa N, Sosothikul D, Chantratita W, Pakakasama S

Abstract
In the present study, we used exome sequencing to analyze PRF1, UNC13D, STX11, and STXBP2, as well as genes associated with primary immunodeficiency disease (RAB27A, LYST, AP3B1, SH2D1A, ITK, CD27, XIAP, and MAGT1) in Thai children with hemophagocytic lymphohistiocytosis (HLH). We performed mutation analysis of HLH-associated genes in 25 Thai children using an exome sequencing method. Genetic variations found within these target genes were compared to exome sequencing data from 133 healthy individuals. Variants identified with minor allele frequencies <5% and novel mutations were confirmed using Sanger sequencing. Exome sequencing data revealed 101 non-synonymous single nucleotide polymorphisms (SNPs) in all subjects. These SNPs were classified as pathogenic (n = 1), likely pathogenic (n = 16), variant of unknown significance (n = 12), or benign variant (n = 72). Homozygous, compound heterozygous, and double-gene heterozygous variants, involving mutations in PRF1 (n = 3), UNC13D (n = 2), STXBP2 (n = 3), LYST (n = 3), XIAP (n = 2), AP3B1 (n = 1), RAB27A (n = 1), and MAGT1 (n = 1), were demonstrated in 12 patients. Novel mutations were found in most patients in this study. In conclusion, exome sequencing demonstrated the ability to identify rare genetic variants in HLH patients. This method is useful in the detection of mutations in multi-gene associated diseases.

PMID: 28353193 [PubMed – as supplied by publisher]

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Tuberculosis in a case of hyper immunoglobulin E syndrome.

J Family Med Prim Care. 2016 Oct-Dec;5(4):871-872

Authors: Ashtekar R, Shah I

Abstract
Hyper immunoglobulin E syndrome (HIES) is a rare primary immunodeficiency disorder characterized by elevated serum IgE, dermatitis, and immunodeficiency that predisposes to multiple skin and lung infections. The most frequent pathogen responsible for infections in these patients is Staphylococcus aureus. Tuberculosis (TB) in patients with HIES is an uncommon finding, and there are only a few reports of mycobacterial infections in known cases of HIES. We present a case of abdominal TB that developed in a 15-year-old boy who also had HIES.

PMID: 28349010 [PubMed – in process]

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British Lung Foundation/United Kingdom Primary Immunodeficiency Network Consensus Statement on the Definition, Diagnosis, and Management of Granulomatous-Lymphocytic Interstitial Lung Disease in Common Variable Immunodeficiency Disorders.

J Allergy Clin Immunol Pract. 2017 Mar 25;:

Authors: Hurst JR, Verma N, Lowe D, Baxendale HE, Jolles S, Kelleher P, Longhurst HJ, Patel SY, Renzoni EA, Sander CR, Avery GR, Babar JL, Buckland MS, Burns S, Egner W, Gompels MM, Gordins P, Haddock JA, Hart SP, Hayman GR, Herriot R, Hoyles RK, Huissoon AP, Jacob J, Nicholson AG, Rassl DM, Sargur RB, Savic S, Seneviratne SL, Sheaff M, Vaitla PM, Walters GI, Whitehouse JL, Wright PA, Condliffe AM

Abstract
A proportion of people living with common variable immunodeficiency disorders develop granulomatous-lymphocytic interstitial lung disease (GLILD). We aimed to develop a consensus statement on the definition, diagnosis, and management of GLILD. All UK specialist centers were contacted and relevant physicians were invited to take part in a 3-round online Delphi process. Responses were graded as Strongly Agree, Tend to Agree, Neither Agree nor Disagree, Tend to Disagree, and Strongly Disagree, scored +1, +0.5, 0, -0.5, and -1, respectively. Agreement was defined as greater than or equal to 80% consensus. Scores are reported as mean ± SD. There was 100% agreement (score, 0.92 ± 0.19) for the following definition: “GLILD is a distinct clinico-radio-pathological ILD occurring in patients with [common variable immunodeficiency disorders], associated with a lymphocytic infiltrate and/or granuloma in the lung, and in whom other conditions have been considered and where possible excluded.” There was consensus that the workup of suspected GLILD requires chest computed tomography (CT) (0.98 ± 0.01), lung function tests (eg, gas transfer, 0.94 ± 0.17), bronchoscopy to exclude infection (0.63 ± 0.50), and lung biopsy (0.58 ± 0.40). There was no consensus on whether expectant management following optimization of immunoglobulin therapy was acceptable: 67% agreed, 25% disagreed, score 0.38 ± 0.59; 90% agreed that when treatment was required, first-line treatment should be with corticosteroids alone (score, 0.55 ± 0.51).

PMID: 28351785 [PubMed – as supplied by publisher]

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A Novel Heterozygous Mutation in the STAT1 SH2 Domain Causes Chronic Mucocutaneous Candidiasis, Atypically Diverse Infections, Autoimmunity, and Impaired Cytokine Regulation.

Front Immunol. 2017;8:274

Authors: Meesilpavikkai K, Dik WA, Schrijver B, Nagtzaam NM, van Rijswijk A, Driessen GJ, van der Spek PJ, van Hagen PM, Dalm VA

Abstract
Chronic mucocutaneous candidiasis (CMC) is a primary immunodeficiency characterized by persistent or recurrent skin and mucosal surface infections with Candida species. Different gene mutations leading to CMC have been identified. These include various heterozygous gain-of-function (GOF) mutations in signal transducer and activator of transcription 1 (STAT1) that are not only associated with infections but also with autoimmune manifestations. Recently, two STAT1 GOF mutations involving the Src homology 2 (SH2) domain have been reported, while so far, over 50 mutations have been described mainly in the coiled coil and the DNA-binding domains. Here, we present two members of a Dutch family with a novel STAT1 mutation located in the SH2 domain. T lymphocytes of these patients revealed STAT1 hyperphosphorylation and higher expression of STAT1 target genes. The clinical picture of CMC in our patients could be explained by diminished production of interleukin (IL)-17 and IL-22, cytokines important in the protection against fungal infections.

PMID: 28348565 [PubMed – in process]

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Delay in diagnosis affects the clinical outcome in a cohort of cvid patients with marked reduction of iga serum levels.

Clin Immunol. 2017 Mar 24;:

Authors: Vincenzo G, Antonio P, Ilaria M, Giuseppe Q, Arturo G, Claudio B, Mariano P, Spadaro G

Abstract
Common variable immunodeficiency disorders (CVID) represent a collection of diseases leading to an absent or strongly impaired antibody production. CVID presents a wide range of immunological abnormalities and clinical manifestations, including infections, inflammatory and autoimmune diseases, and malignancies. The aim of this observational study was to analyze the epidemiological and clinical features of a cohort of 75 Italian CVID patients, and evaluate the correlation with comorbidity and mortality. Clinical data were retrospectively collected: the cohort was followed-up for a maximum of 30years (mean time of 10.24years, median of 9years). An higher age at the diagnosis of CVID and an higher age at onset of symptoms were significantly associated with a reduction of patients survival if stratified per median of IgA (less than or >8.00mg/dl). Thus IgA levels at diagnosis are correlated with patients survival contributing to identify a subset with a worse prognostic outcome.

PMID: 28347823 [PubMed – as supplied by publisher]

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