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Reversal of Immunoglobulin A Deficiency in Children.

November 6, 2014 By Manish Butte

Reversal of Immunoglobulin A Deficiency in Children.

J Clin Immunol. 2014 Nov 5;

Authors: Lim CK, Dahle C, Elvin K, Andersson BA, Rönnelid J, Melén E, Bergström A, Truedsson L, Hammarström L

Abstract
PURPOSE: Immunoglobulin A deficiency (IgAD) is the most common primary immunodeficiency in the general population. It is defined as a serum IgA level below or equal to 0.07 g/l with normal IgM and IgG levels in children over the age of 4. However, a few cases of reversal of IgAD at later ages have been observed previously, especially in pediatric patients. This study aimed at investigating the frequency of reversal in a large cohort of children and young adults in order to evaluate the present definition of IgAD.
METHODS: Clinical laboratory records from 654 pediatric IgA deficient patients, 4-13 years of age, were retrieved from five university hospitals in Sweden. Follow up in the children where IgA serum levels had been routinely measured was subsequently performed. In addition, follow up of the IgA-levels was also performed at 4, 8 and 16 years of age in children who were IgA deficient at the age of 4 years in a Swedish population-based birth cohort study in Stockholm (BAMSE).
RESULTS: Nine out of 39 (23.1 %) children who were identified as IgAD at 4 years of age subsequently increased their serum IgA level above 0.07 g/L. The average age of reversal was 9.53 ± 2.91 years. In addition, 30 out of the 131 (22.9 %) children with serum IgAD when sampled between 5 and 9.99 years of age reversed their serum IgA level with time. The BAMSE follow up study showed a reversal of IgAD noted at 4 years of age in 8 out of 14 IgAD children at 16 years of age (5 at 8 years of age) where 4 were normalized their serum IgA levels while 4 still showed low serum levels of IgA, yet above the level defining IgAD. The results indicate that using 4 years of age, as a cut off for a diagnosis of IgAD may not be appropriate.
CONCLUSIONS: Our findings suggest that a diagnosis of IgAD should not be made before the early teens using 0.07 g/L of IgA in serum as a cut off.

PMID: 25370723 [PubMed – as supplied by publisher]

Dramatic Improvement in the Multifocal Positron Emission Tomography Findings of a Young Adult with Chronic Granulomatous Disease Following Allogeneic Hematopoietic Stem Cell Transplantation.

November 5, 2014 By Manish Butte

Dramatic Improvement in the Multifocal Positron Emission Tomography Findings of a Young Adult with Chronic Granulomatous Disease Following Allogeneic Hematopoietic Stem Cell Transplantation.

J Clin Immunol. 2014 Nov 4;

Authors: Shigemura T, Nakazawa Y, Hirabayashi K, Kobayashi N, Sakashita K, Agematsu K, Koike K

Abstract
Chronic granulomatous disease (CGD) is a primary immunodeficiency caused by defects of nicotinamide adenine dinucleotide phosphate oxidase. Catalase-positive bacteria and fungi are phagocytosed, but persist within phagocytes, resulting in granulomatous inflammation. Although allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment for CGD, HSCT sometimes leads to fatal outcomes related to the exacerbation of persistent infectious or post-infectious inflammatory diseases, particularly in adolescent and young adult patients with a history of recurrent infections and/or multiple granulomas in organs. Here, we present the case of a young adult with X-linked CGD in whom multiple lesions were found in lungs and lymph nodes on both computed tomography and positron emission tomography (PET) scans before allogeneic HSCT, but all the lesions disappeared only on PET scan 5 months after HSCT. Monitoring the activity of multiple pre-existing lesions with PET scan may be beneficial to adolescent and young adult CGD-patients undergoing allogeneic HSCT.

PMID: 25367170 [PubMed – as supplied by publisher]

Integration Site and Clonal Expansion in Human Chronic Retroviral Infection and Gene Therapy.

November 5, 2014 By Manish Butte

Integration Site and Clonal Expansion in Human Chronic Retroviral Infection and Gene Therapy.

Viruses. 2014;6(11):4140-4164

Authors: Niederer HA, Bangham CR

Abstract
Retroviral vectors have been successfully used therapeutically to restore expression of genes in a range of single-gene diseases, including several primary immunodeficiency disorders. Although clinical trials have shown remarkable results, there have also been a number of severe adverse events involving malignant outgrowth of a transformed clonal population. This clonal expansion is influenced by the integration site profile of the viral integrase, the transgene expressed, and the effect of the viral promoters on the neighbouring host genome. Infection with the pathogenic human retrovirus HTLV-1 also causes clonal expansion of cells containing an integrated HTLV-1 provirus. Although the majority of HTLV-1-infected people remain asymptomatic, up to 5% develop an aggressive T cell malignancy. In this review we discuss recent findings on the role of the genomic integration site in determining the clonality and the potential for malignant transformation of cells carrying integrated HTLV-1 or gene therapy vectors, and how these results have contributed to the understanding of HTLV-1 pathogenesis and to improvements in gene therapy vector safety.

PMID: 25365582 [PubMed – as supplied by publisher]

Hyper-IgE syndromes: reviewing PGM3 deficiency.

November 5, 2014 By Manish Butte

Hyper-IgE syndromes: reviewing PGM3 deficiency.

Curr Opin Pediatr. 2014 Dec;26(6):697-703

Authors: Yang L, Fliegauf M, Grimbacher B

Abstract
PURPOSE OF REVIEW: The hyper-IgE syndromes have been recognized as a group of primary immunodeficiencies characterized by eczema, recurrent skin and lung infections, and elevated serum IgE. Recently, mutations in phosphoglucomutase 3 (encoding PGM3, which is involved in the protein glycosylation pathway) have been identified in autosomal recessive forms of hyper-IgE syndromes.
RECENT FINDINGS: Autosomal recessive, hypomorphic PGM3 mutations cause a multisystem disorder, characterized by both a congenital glycosylation disease and a hyper-IgE syndrome. The reported mutations in PGM3 led to an impaired biosynthesis of UDP-GlcNAc and impaired tri-antennary and tetra-antennary N-glycan structures. Laboratory results in patients showed eosinophilia, a T-cell proliferation defect, and a reversed CD4/CD8 ratio. The impaired glycosylation in PGM3-mutant patients will not only affect proteins involved in the immune system, and thus causes a multisystem phenotype.
SUMMARY: The identification of hyper-IgE syndromes-associated mutations in PGM3 provides the basis for future studies on the pathophysiology and the molecular mechanisms of eczema, IgE dysregulation, and increased susceptibility to infections.

PMID: 25365149 [PubMed – in process]

Invasive pneumococcal disease in children can reveal a primary immunodeficiency.

November 5, 2014 By Manish Butte

Invasive pneumococcal disease in children can reveal a primary immunodeficiency.

Pediatrics. 2014 Nov;134 Suppl 3:S180-1

Authors: Fleisher TA

PMID: 25363989 [PubMed – in process]

Survey of early complications of primary skin graft and secondary skin graft (delayed) surgery after resection of burnwaste in hospitalized burn patients.

November 5, 2014 By Manish Butte

Survey of early complications of primary skin graft and secondary skin graft (delayed) surgery after resection of burnwaste in hospitalized burn patients.

Glob J Health Sci. 2014;6(7 Spec No):38456

Authors: Enshaei A, Masoudi N

Abstract
INTRODUCTION: Burning is the second most common cause of home injuries in Iran that is often the cause of conflicts between children and young adults. Burning can lead to early and late complications that scar and contracture are the most common. Burn waste treatment is done by two methods: excision and then skin graft after the formation of granulation tissue; and excision and graft simultaneously that in this study, these two methods are compared.
METHODS: This was performed as a quasi-experimental analysis and retrospective study on all patients who were hospitalized for burn scar. All patients who have associated with weak eningimmune diseases such as diabetes, acquired immunodeficiency or congenital, taking steroids and patients undergoing chemotherapy etc. are excluded. The method of grafting in patients is primary graft procedure that was compared with patients who are treated using secondary graft. Data collected through review of patients’ hospital and clinic chart.
RESULTS: The mean burn percentage in the primary repair group was 14.4% and in the delayed repair group was 16.6%, respectively. The incidence of hematoma in both groups was zero. Skin necrosis and graft rejection and infection in the primary repair group was in 3.7% of patients and in the delayed repair group was in 1.2% of cases (P=0.5) CONCLUSION: Based on the findings of this study, no difference was observed between the two methods of excision and primary graft with delayed graft in the incidence of graft rejection. Due to the shorter treatment of primary graft and patient satisfaction and also according to the findings of this study excision and primary graft method seems appropriate method for treating old waste burning.

PMID: 25363185 [PubMed – in process]

Recurrent meningitis in a child with IgG3 subclass deficiency.

November 5, 2014 By Manish Butte

Recurrent meningitis in a child with IgG3 subclass deficiency.

J Pak Med Assoc. 2014 Aug;64(8):963-5

Authors: Vehapoglu A, Ozgurhan G, Demir AD, Uzuner S, Nursoy MA, Turkmen S

Abstract
Recurrent meningitis is an uncommon life-threatening condition. Here, the case of a 6-year-old boy is reported who had two episodes of meningitis with an IgG3 subclass deficiency. The boy had aseptic meningitis at the age of 3 years, followed by bacterial meningitis at the age of 4 years. Primary immunoglobulin deficiencies are a group of disorders associated with an increased incidence and/or severity of infection. Recurrent infections, sinusitis, bronchitis, and pneumonia are the most frequently observed illnesses in patients with IgG subclass deficiencies, of which an IgG3 subclass deficiency is the most common, especially in adults. Although cases of recurrent viral or bacterial meningitis have been reported, herein a patient is presented with recurrence of aseptic and bacterial meningitis 1 year after the initial episode. Some researchers recommend that all children with episodes of recurrent meningitis should be screened for primary immunoglobulin or complement deficiencies.

PMID: 25252530 [PubMed – indexed for MEDLINE]

Addressing diagnostic challenges in primary immunodeficiencies: laboratory evaluation of Toll-like receptor- and NF-κB-mediated immune responses.

November 5, 2014 By Manish Butte

Addressing diagnostic challenges in primary immunodeficiencies: laboratory evaluation of Toll-like receptor- and NF-κB-mediated immune responses.

Crit Rev Clin Lab Sci. 2014 Apr;51(2):112-23

Authors: Frans G, Meyts I, Picard C, Puel A, Zhang SY, Moens L, Wuyts G, Van der Werff Ten Bosch J, Casanova JL, Bossuyt X

Abstract
Toll-like receptors (TLRs) play an important role in immunity and mediate their actions via multiple signaling pathways, in particular, the nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF-κB) pathway. Rare inherited defects of TLR- and NF-κB-dependent responses have recently been recognized. These primary immunodeficiencies predispose children to life-threatening infections and often remain undiagnosed. Establishing a sensitive, specific, cost-effective and simple method for diagnosis is therefore important. In this article, we review the known defects of TLR- and NF-κB-mediated pathways and the assays that can be used to screen for such defects.

PMID: 24533908 [PubMed – indexed for MEDLINE]

Low-dose serotherapy improves early immune reconstitution after cord blood transplantation for primary immunodeficiencies.

November 5, 2014 By Manish Butte

Low-dose serotherapy improves early immune reconstitution after cord blood transplantation for primary immunodeficiencies.

Biol Blood Marrow Transplant. 2014 Feb;20(2):243-9

Authors: Lane JP, Evans PT, Nademi Z, Barge D, Jackson A, Hambleton S, Flood TJ, Cant AJ, Abinun M, Slatter MA, Gennery AR

Abstract
Cord blood transplantation (CBT) is curative for many primary immunodeficiencies (PIDs) but is associated with risks of viral infection and graft-versus-host disease (GvHD). Serotherapy reduces GvHD but potentially increases the risk of viral infection by delaying immune reconstitution. Because many PID patients have pre-existing viral infections, the optimal dose of serotherapy is unclear. We performed a retrospective analysis in 34 consecutive PID patients undergoing CBT and compared immune reconstitution, viral infection, GvHD, mortality, and long-term immune function between high-dose (n = 11) and low-dose (n = 9) serotherapy. Serotherapy dose had no effect on neutrophil engraftment. Median CD3(+) engraftment occurred at 92.5 and 97 days for high- and low-dose serotherapy, respectively. The low-dose serotherapy group had higher CD3(+), CD4(+), and early thymic emigrant counts at 4 months compared with the high-dose group. GvHD severity and number of viral infections did not differ between serotherapy doses. Survival from the transplantation process was 90.9% for high-dose and 100% for low-dose groups. In conclusion, low-dose serotherapy enhanced T cell reconstitution and thymopoiesis during the first year after CBT with no increase in GvHD.

PMID: 24225641 [PubMed – indexed for MEDLINE]

Do Immunocompromised Children Benefit from Having Surgical Lung Biopsy Performed?

November 2, 2014 By Manish Butte

Do Immunocompromised Children Benefit from Having Surgical Lung Biopsy Performed?

Acta Haematol. 2014 Oct 29;133(2):205-209

Authors: Goldstein G, Keller N, Bilik R, Bielorai B, Toren A

Abstract
Background: Surgical lung biopsy is considered a gold standard for the evaluation of pulmonary disease in immunocompromised children. However, in the literature, its accuracy and the rate of complications vary. Objective: We aimed to evaluate the yield of surgical lung biopsies in the management of persistent pulmonary findings in immunocompromised children. Methods: We performed a retrospective review of clinical records of immunocompromised children who underwent surgical lung biopsies, and evaluated the impact that preoperative factors had on outcomes. Results: Twenty-five patients underwent 27 surgical lung biopsies. The underlying immunodeficiency included allogeneic stem cell transplantation (n = 12), chemotherapy for solid tumors (n = 6), hematologic malignancy (n = 4), primary immunodeficiency (n = 4) and chronic steroid use (n = 1). Biopsies provided a specific histopathologic or microbiologic diagnosis in 10 cases (37%). No preoperative factor predicted a diagnostic biopsy. Five of the 27 biopsies were beneficial for the patients (18%). A major complication related to the procedure was reported for 1 biopsy (4%). Conclusions: We conclude that surgical lung biopsy in pediatric immunocompromised patients appears to be safe, but has a relatively low diagnostic yield and an even lower yield with regards to the benefit it provides. © 2014 S. Karger AG, Basel.

PMID: 25358357 [PubMed – as supplied by publisher]