Research

Health-Related Quality of Life in Adult Patients with Common Variable Immunodeficiency Disorders and Impact of Treatment.

J Clin Immunol. 2017 May 23;:

Authors: Rider NL, Kutac C, Hajjar J, Scalchunes C, Seeborg FO, Boyle M, Orange JS

Abstract
PURPOSE: Common variable immunodeficiency disorder (CVID) is a primary immunodeficiency disease (PIDD) often associated with severe and chronic infections. Patients commonly receive immunoglobulin (Ig) treatment to reduce the cycle of recurrent infection and improve physical functioning. However, how Ig treatment in CVID affects quality of life (QOL) has not been thoroughly evaluated. The purpose of a recent Immune Deficiency Foundation (IDF) mail survey was to assess the factors that are associated with QOL in patients with CVID receiving Ig treatment.
METHODS: A 75-question survey developed by the IDF and a 12-item Short Form Health Survey (SF-12) to assess QOL were mailed to adults with CVID. Mean SF-12 scores were compared between patients with CVID and the general US adult population normative sample.
RESULTS: Overall, 945 patients with CVID completed the surveys. More than half of the patients (54.9%) received intravenous Ig and 44.9% received subcutaneous Ig treatment. Patients with CVID had significantly lower SF-12 scores compared with the general US population regardless of sex or age (p < 0.05). Route of IgG replacement did not dramatically improve QOL. SF-12 scores were highest in patients with CVID who have well-controlled PIDD, lacked physical impairments, were not bothered by treatment, and received Ig infusions at home.
CONCLUSION: These data provide insight into what factors are most associated with physical and mental health, which can serve to improve QOL in patients in this population. Improvements in QOL can result from early detection of disease, limiting digestive system disease, attention to fatigue, and implementation of an individual treatment plan for the patient.

PMID: 28536745 [PubMed – as supplied by publisher]

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Abnormal distribution of distinct lymphocyte subsets in children with Wiskott-Aldrich syndrome.

Hum Immunol. 2017 May 20;:

Authors: Zhou L, Li W, Zhang X, Liu D, Ding Y, Dai R, Zhao X

Abstract
Wiskott-Aldrich syndrome (WAS) is a severe and rare primary immunodeficiency. Several studies show that WAS protein (WASp) plays a key role in the function of certain lymphocyte subsets. So far, no study has described distinct immunophenotypic abnormalities associated with WAS; thus the prognostic significance of any such abnormalities is unclear. This study examined many differences in the percentage/absolute numbers of distinct lymphocyte subsets in 20 WAS patients and 20 age/sex-matched healthy controls, and analyzed the association between these abnormalities and clinical disease scores. The results showed that the numbers of CD4(+)T cells, B cells, and CD8(+)naïveT cells were significantly lower in WAS patients; furthermore, the numbers in WASp-negative patients were lower than those in WASp-positive patients. WAS patients showed a selective reduction in expression of CD19 by naïve and transitional B cells. There was a negative association between the number of B cells and the WAS clinical scores. Also, CD8(+)naïveT cell numbers in patients with a score of 3-5Awere lower than those in patients with a score of 2. The absence of WASp leads to a reduction in the population of specific lymphocyte subsets; therefore, these findings may help future management of patients with WAS.

PMID: 28535968 [PubMed – as supplied by publisher]

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Developing Inference Model to Diagnosis of Primary Immunodeficiency Diseases in Protégé.

Acta Med Iran. 2017 Apr;55(4):280-281

Authors: Sepehri F, Langarizadeh M, Sharifi L, Azizi G, Safdari R, Aghamohammadi A

PMID: 28532143 [PubMed – in process]

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Immunoglobulin-induced hemolysis, splenomegaly and inflammation in patients with antibody deficiencies.

Expert Rev Clin Immunol. 2016 Jul;12(7):725-31

Authors: Pulvirenti F, Granata G, Girelli G, Quinti I

Abstract
IgG replacement for primary antibody deficiencies is a safe treatment administered to prevent recurrent infections and reduce mortality. Recently, several reports described acute hemolytic episodes following IgG administration due to a passive transfer of blood group alloantibodies, including anti-A, anti-B, as well as anti-Rh antibodies. Here, we reviewed and discussed the consequences of passively transferred RBCs antibodies. The chronic passive transfer of alloantibodies might also cause a subclinical condition due to a compensated extravascular chronic hemolysis with poorly understood consequences. This phenomenon might possibly represent an unrecognized cause of splenomegaly and might contribute to inflammation in patients with primary antibody deficiencies.

PMID: 26854522 [PubMed – indexed for MEDLINE]

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BACH2 immunodeficiency illustrates an association between super-enhancers and haploinsufficiency.

Nat Immunol. 2017 May 22;:

Authors: Afzali B, Grönholm J, Vandrovcova J, O’Brien C, Sun HW, Vanderleyden I, Davis FP, Khoder A, Zhang Y, Hegazy AN, Villarino AV, Palmer IW, Kaufman J, Watts NR, Kazemian M, Kamenyeva O, Keith J, Sayed A, Kasperaviciute D, Mueller M, Hughes JD, Fuss IJ, Sadiyah MF, Montgomery-Recht K, McElwee J, Restifo NP, Strober W, Linterman MA, Wingfield PT, Uhlig HH, Roychoudhuri R, Aitman TJ, Kelleher P, Lenardo MJ, O’Shea JJ, Cooper N, Laurence ADJ

Abstract
The transcriptional programs that guide lymphocyte differentiation depend on the precise expression and timing of transcription factors (TFs). The TF BACH2 is essential for T and B lymphocytes and is associated with an archetypal super-enhancer (SE). Single-nucleotide variants in the BACH2 locus are associated with several autoimmune diseases, but BACH2 mutations that cause Mendelian monogenic primary immunodeficiency have not previously been identified. Here we describe a syndrome of BACH2-related immunodeficiency and autoimmunity (BRIDA) that results from BACH2 haploinsufficiency. Affected subjects had lymphocyte-maturation defects that caused immunoglobulin deficiency and intestinal inflammation. The mutations disrupted protein stability by interfering with homodimerization or by causing aggregation. We observed analogous lymphocyte defects in Bach2-heterozygous mice. More generally, we observed that genes that cause monogenic haploinsufficient diseases were substantially enriched for TFs and SE architecture. These findings reveal a previously unrecognized feature of SE architecture in Mendelian diseases of immunity: heterozygous mutations in SE-regulated genes identified by whole-exome/genome sequencing may have greater significance than previously recognized.

PMID: 28530713 [PubMed – as supplied by publisher]

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Advances in the Care of Primary Immunodeficiencies (PIDs): from Birth to Adulthood.

J Clin Immunol. 2017 May 18;:

Authors: Mahlaoui N, Warnatz K, Jones A, Workman S, Cant A

Abstract
Primary immunodeficiencies (PIDs) are a widely heterogeneous group of inherited defects of the immune system consisting of many clinical phenotypes with at least 300 underlying genetic deficits currently known. Patients with PIDs can present with, or develop during the course of their life, a susceptibility to recurrent and chronic infection along with autoimmune, allergic, inflammatory, and/or proliferative disorders, all potentially leading to end-organ damage. In recent years, a combination of basic and clinical research has greatly improved understanding of the underlying immunological and genetic defects in PIDs, leading to improved diagnosis, classification, and treatment approaches. In this review, we consider some of the key understandings that should direct diagnostic and treatment approaches in PID and offer insights into current and emerging management approaches and the lifelong care of patients from childhood through to adulthood.

PMID: 28523402 [PubMed – as supplied by publisher]

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Disseminated Bacillus Calmette-Guérin Osteomyelitis in Twin Sisters Related to STAT1 Gene Deficiency.

Pediatr Dev Pathol. 2017 Jun;20(3):255-261

Authors: Boudjemaa S, Dainese L, Héritier S, Masserot C, Hachemane S, Casanova JL, Coulomb A, Bustamante J

Abstract
Mendelian susceptibility to mycobacterial disease is a rare syndrome characterized by severe clinical infections usually caused by weakly virulent mycobacterial species such as Bacillus Calmette-Guérin vaccines and environmental nontuberculous mycobacteria or more virulent mycobacteria as mycobacterium tuberculosis. Since 1996, 9 genes including 7 autosomal ( STAT1, IFNGR1, IFNGR2, IL12B, IL12RB1, ISG15, and IRF8) and 2 X-linked genes ( NEMO and CYBB) have been identified. Allelic heterogeneity leaded to recognize about 18 genetic diseases with variable clinical phenotypes, but sharing a same physiological mechanism represented by a defect in human IL-12-dependant-INF-γ-mediated immunity. We report here a case of multifocal Bacillus Calmette-Guérin osteomyelitis in a context Mendelian susceptibility to mycobacterial disease mimicking a metastatic neuroblastoma in a child presenting with delayed growth. The investigation of her twin sister showed the same disease. A heterozygous mutation in exon 22 of STAT1 gene was found in both sisters, another sister and the father being healthy and heterozygous for the same mutation.

PMID: 28521627 [PubMed – in process]

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Another subcutaneous immune globulin (Cuvitru) for primary immunodeficiency.

Med Lett Drugs Ther. 2017 May 22;59(1521):e88-e89

Authors:

PMID: 28520701 [PubMed – in process]

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IBD due to PID: Inflammatory bowel disease caused by primary immunodeficiencies – Clinical presentations, review of literature, and proposal of a rational diagnostic algorithm.

Pediatr Allergy Immunol. 2017 May 17;:

Authors: Tegtmeyer D, Seidl M, Gerner P, Baumann U, Klemann C

Abstract
Inflammatory bowel diseases (IBD) including Crohn’s disease (CD) and ulcerative colitis (UC) have a multifactorial pathogenesis with complex interactions between polygenetic predispositions and environmental factors. However, IBD can also be caused by monogenic diseases, such as primary immunodeficiencies (PID). Recently, an increasing number of these altogether rare diseases has been described to present often primarily, or solely as IBD. Early recognition of these conditions enables adaption of therapies and thus directly benefits the course of IBDs. Here, we discuss the different clinical presentations in IBD and characteristic features of patient’s history, clinical findings, and diagnostic results indicative for a causative PID. Possible predictors are early onset of disease, necessity of parenteral nutrition, failure to respond to standard immunosuppressive therapy, parental consanguinity, increased susceptibility for infections, certain histopathologic findings, and blood tests that are atypical for classic IBD. We illustrate this with exemplary case studies of IBD due to NEMO deficiency, chronic granulomatous disease (CGD), common variable immunodeficiency (CVID), CTLA-4 and LRBA deficiency. Taking these factors into account, we propose a diagnostic pathway to enable early diagnosis of IBD due to PID. This article is protected by copyright. All rights reserved.

PMID: 28513998 [PubMed – as supplied by publisher]

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