Research

IRIS as a post-transplantation complication in primary immunodeficiency with disseminated M. avium.

Clin Infect Dis. 2019 Jun 12;:

Authors: Manion M, Dimitrova D, Pei L, Gea-Banacloche J, Zelazny A, Lisco A, Zerbe C, Freeman AF, Holland SM, Kanakry CG, Kanakry JA, Sereti I

Abstract
Patients with primary immunodeficiencies undergoing allogeneic hematopoietic cell transplantation (HCT) for difficult-to-control infections can experience immune reconstitution inflammatory syndrome (IRIS) following engraftment. We describe three patients with post-HCT IRIS related to mycobacterial infection, with in vitro data demonstrating emergence of pathogen-specific immune responses and concomitant rise in plasma inflammatory markers.

PMID: 31190050 [PubMed – as supplied by publisher]

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Neuropsychiatric Manifestation of Addison’s Disease: A Rare Case Report.

Cureus. 2019 Apr 01;11(4):e4356

Authors: Munawar M, Iftikhar PM, Hasan CA, Sohail CS, Rizvi SW

Abstract
Addison’s disease (AD), also known as primary adrenal insufficiency, is a rare autoimmune disorder affecting males and females equally. The most common cause of AD is autoimmune adrenalitis and other causes include metastatic cancers, tuberculosis and acquired immunodeficiency syndrome. AD presents with a wide variety of signs and symptoms and thus, making a diagnosis challenging. The common symptoms of this disease include weakness and fatigability, orthostatic hypotension, nausea, vomiting, diarrhea, anorexia and weight loss. Addison’s disease often presented with other autoimmune disorders, such as autoimmune polyglandular syndrome. We herein report a case of a patient who presented in a hospital emergency department, with Addisonian crisis and predominant neuropsychiatric manifestation. On review of the patient’s history, combined with biochemical testing, a diagnosis of Addison’s disease was established. This type of presentation is relatively uncommon.

PMID: 31192061 [PubMed]

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Association between primary immunodeficiency and asthma exacerbation in adult asthmatics.

Korean J Intern Med. 2019 Jun 14;:

Authors: Lee SH, Ban GY, Kim SC, Chung CG, Lee HY, Lee JH, Park HS

Abstract
Background/Aims: Primary immunodef iciency (PID) is a serious comorbid condition in adult asthmatics that have frequent exacerbations, which requires monthly replacement of intravenous immunoglobulin (IVIG). However, the prevalence and clinical significance of PID in adult asthmatics in Korea have not yet been reported. The aim of this study is to assess the prevalence of PID and its association with asthma exacerbation in Korean adult asthmatics.
Methods: A total of 2,866 adult asthmatics were enrolled in this study. The PID group was defined as subjects who had lower levels of immunoglobulin G (IgG)/ A/M and/or IgG subclass presenting with recurrent respiratory infections. Serum samples were assayed for total IgG/A/M by immunoturbidimetry, and IgG subclasses by nephelometry.
Results: Of the 2,866 asthmatic patients enrolled, 157 (5.49%) had PID (classified as the PID group), while those without PID was classified as the non-PID group. IgG subclass deficiency (58%) is most prevalent, among which IgG3 subclass deficiency was most common (58%). The relative risk of asthma exacerbation was 1.70 times higher in the PID group compared to the non-PID group (1.696; 95% confidence interval, 1.284 to 2.239; p < 0.001); the prevalence of severe asthma was significantly higher in the PID group than in the non-PID group (32.48% vs. 13.00%, p < 0.001). Thirty-five among 157 patients in the PID group d maintained IVIG to prevent asthma exacerbation.
Conclusions: It is suggested that PID, especially IgG3 subclass deficiency, is a significant risk factor for asthma exacerbation. Screening of IgG subclass levels and IVIG replacement should be considered in the management in adult asthmatics.

PMID: 31185709 [PubMed – as supplied by publisher]

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Disturbed Transcription of TLRs’ Negative Regulators and Cytokines Secretion among TLR4- and 9-Activated PBMCs of Agammaglobulinemic Patients.

Immunol Invest. 2019 Jun 11;:1-15

Authors: Sanaei R, Rezaei N, Aghamohammadi A, Delbandi AA, Tavasolian P, Tajik N

Abstract
Toll-like receptors (TLRs) are inevitable elements for immunity development and antibody production. TLRs are in close interaction with Bruton’s tyrosine kinase which has been found mutated and malfunctioned in the prototype antibody deficiency disease named X-linked agammaglobulinemia (XLA). TLRs’ ability was evaluated to induce transcription of TLR-negative regulators, including suppressor of cytokine signaling 1 (SOCS1), interleukin-1 receptor-associated kinase 3 (IRAK-M), tumor necrosis factor alpha-induced protein 3 (TNFAIP3, A20), and Ring finger protein 216 (RNF216), and Tumor necrosis factor-α (TNF-α) and Interferon-α (IFN-α) production via Lipopolysaccharides (LPS) and CpG-A oligodeoxynucleotides (CpG-A ODN). Measured by TaqMan real-time polymerase chain reaction (PCR), meaningfully increased transcripts of SOCS1 and RNF216 were found in XLA peripheral blood mononuclear cells (PBMCs). Also, TLR inductions of XLA have led to similar downregulations in the regulator’s transcription which was different from that in healthy donors. Cytokine measurement by enzyme-linked immunosorbent assay (ELISA) revealed a significant lower TNF-α production both before and after LPS. By selected molecules in this study, TLRs’ potential defectiveness range expands TLRs expression, downstream signaling, and cytokine production. The results show new potential elements that could play a part in TLRs defect and pathogenesis of agammaglobulinemia as well.

PMID: 31185757 [PubMed – as supplied by publisher]

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Respiratory Complications in Patients with Hyper IgM Syndrome.

J Clin Immunol. 2019 Jun 11;:

Authors: Moazzami B, Yazdani R, Azizi G, Kiaei F, Tafakori M, Modaresi M, Shirzadi R, Mahdaviani SA, Sohani M, Abolhassani H, Aghamohammadi A

Abstract
PURPOSE: Hyper Immunoglobulin M (HIgM) syndrome is a heterogeneous group of primary immunodeficiency disorders, characterized by recurrent infections and associated with decreased serum IgG and IgA, but normal or increased IgM. The aim of the present study was to evaluate respiratory manifestations in patients with HIgM syndrome.
METHODS: A total number of 62 patients, including 46 males and 16 females were included in the present study. To investigate the respiratory complications among HIgM patients, we evaluated the clinical hospital records, immunologic and molecular diagnostic assays, pulmonary function tests (PFT), and high-resolution computed tomography (HRCT) scans.
RESULTS: Pneumonia was the most common respiratory manifestation (n = 35, 56.4%), followed by otitis media (45.1%), sinusitis (33.8%), and bronchiectasis (14.5%). 52.1% of the patients had abnormal PFT results, with a predominant restrictive pattern of changes. HRCT scans demonstrated abnormal findings in 85.7% of patients with found mutations. Ten cases had hilar lymphadenopathy and para-hilar infiltrates in their HRCT findings. Genetic diagnosis was confirmed in 29 HIgM patients (72.4% CD40 ligand (CD40L) and 24.1% activation-induced cytidine deaminase (AICDA/AID) deficiencies). Majority of patients with CD40L (71.4%) and AID (57.1%) deficiencies had missense mutations. Pneumonia and abnormal high-resolution computed tomography (HRCT) findings were more frequent among patients with CD40L mutation. Respiratory failure constituted the major cause of mortality (37.5%) with majority of cases occurring in CD40L-deficient patients (50%).
CONCLUSIONS: Respiratory complications are common in patients with HIgM syndrome. A proper awareness of respiratory manifestations in patients with HIgM may result in improved management, reduced morbidity and mortality, and an improvement in the quality of life of the patients.

PMID: 31183658 [PubMed – as supplied by publisher]

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Clinical, genetic, and immunological characteristics of 40 Chinese patients with CD40 ligand deficiency.

Scand J Immunol. 2019 Jun 10;:e12798

Authors: Du X, Tang W, Chen X, Zeng T, Wang Y, Chen Z, Xu T, Zhou L, Tang X, An Y, Zhao X

Abstract
CD40 ligand (CD40L) deficiency is a rare but life-threatening primary immunodeficiency caused by mutations in the CD40L gene. Here, we investigated a cohort of 40 genetically-diagnosed CD40L-deficient patients from the Chinese mainland, analyzed their clinical and genetic data, and examined CD40L expression, the proportion of T cell subsets, B cell subsets, and T follicular helper (Tfh) cells. The aim was to provide a complete picture of CD40L deficiency. Initial presentations of the patient cohort mainly involved recurrent fever (47.5%) and sinopulmonary infection (42.5%). Life-threatening infections (42.5%), caused by various pathogens, were the most serious threats faced by CD40L-deficient patients, while neutropenia (57.5%) remained the most common complication. Opportunistic infections, including Pneumocystis carinii pneumonia and invasive fungal disease associated with Talaromyces marneffei were also common in the cohort. In addition, seven patients (17.5%) suffered BCGitis /BCGosis, which is a major problem facing a planned immunization program in China. It was intriguing that reduced IgM levels were observed in 12.5% of patients, while normal or elevated IgA levels were shown in 47.5% of patients. Thirty-seven unique mutations were identified in 40 patients; of these, 10 were novel. Furthermore, we observed a lower percentage of NK cells, Tfh cells, and central memory CD4+ T cells, and an extremely small class-switched memory B cell population, in CD40L-deficient patients. Patients that underwent hematopoietic stem cell transplantation experienced better disease remission. Taken together, our data establish the largest database about CD40L deficiency in China and provide genetic, immunologic, and clinical information about Chinese CD40L-deficient patients. This article is protected by copyright. All rights reserved.

PMID: 31179555 [PubMed – as supplied by publisher]

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Supporting caregivers during hematopoietic cell transplantation for children with primary immunodeficiency disorders.

J Allergy Clin Immunol. 2019 Jun;143(6):2271-2278

Authors: Yoo J, Halley MC, Lown EA, Yank V, Ort K, Cowan MJ, Dorsey MJ, Smith H, Iyengar S, Scalchunes C, Mangurian C

Abstract
BACKGROUND: Caregivers of children with primary immunodeficiency disorders (PIDs) experience significant psychological distress during their child’s hematopoietic cell transplantation (HCT) process.
OBJECTIVES: This study aims to understand caregiver challenges and identify areas for health care system-level improvements to enhance caregiver well-being.
METHODS: In this mixed-methods study caregivers of children with PIDs were contacted in August to November 2017 through online and electronic mailing lists of rare disease consortiums and foundations. Caregivers were invited to participate in an online survey assessing sociodemographic variables, the child’s medical characteristics, psychosocial support use, and the World Health Organization-5 Well-Being Index. Open-ended questions about health care system improvements were included. Descriptive statistics and linear multivariate regression analyses were conducted. A modified content analysis method was used to code responses and identify emergent themes.
RESULTS: Among the 80 caregiver respondents, caregivers had a median age of 34 years (range, 23-62 years) and were predominantly female, white, and married with male children given a diagnosis of severe combined immune deficiency. In the adjusted regression model lower caregiver well-being was significantly associated with lower household income and medical complications. Challenges during HCT include maintaining relationships with partners and the child’s healthy sibling or siblings, managing self-care, and coping with feelings of uncertainty. Caregivers suggested several organizational-level solutions to enhance psychosocial support, including respite services, online connections to other PID caregivers, and bedside mental health services.
CONCLUSIONS: Certain high-risk subpopulations of caregivers might need more targeted psychosocial support to reduce the long-term effect of the HCT experience on their well-being. Caregivers suggested several organizational-level solutions for provision of this support.

PMID: 31178019 [PubMed – in process]

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