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The benefit of exercise in patients who undergo allogeneic hematopoietic stem cell transplantation.

May 28, 2019 By Manish Butte

The benefit of exercise in patients who undergo allogeneic hematopoietic stem cell transplantation.

J Int Soc Phys Rehabil Med. 2019 Jan-Mar;2(1):54-61

Authors: Morishita S, Tsubaki A, Hotta K, Fu JB, Fuji S

Abstract
Allogeneic hematopoietic stem-cell transplantation (allo-HSCT) is increasingly used in the treatment of hematologic cancers such as leukemias, lymphomas, and myeloma, and for other hematologic disorders such as primary immunodeficiency, aplastic anemia, and myelodysplasia. Allo-HSCT entails a conditioning regimen of frequent high-dose chemotherapy in combination with total body irradiation, followed by infusion of donor-harvested bone marrow or peripheral blood stem cells. As an aggressive and demanding medical therapy that profoundly impacts patient quality of life (QOL), allo-HSCT is associated with numerous treatment-related physical, psychological, and psychosocial side effects. The procedure can result in decreased respiratory and balance function, skeletal muscle strength, and exercise capacity. Thus, as physical exercise has been shown to positively effect physical and psychosocial function and QOL in allo-HSCT patients, it is a recommended intervention for improving essential functions and offsetting lost exercise capacity after the procedure. Furthermore, recent evidence has shown that physical exercise can influence survival rate and mortality in allo-HSCT patients. This review provides an overview of the current research on the effectiveness of physical exercise for allo-HSCT patients.

PMID: 31131374 [PubMed]

Clinical and Laboratory Features of 184 Italian Pediatric Patients Affected with Selective IgA Deficiency (SIgAD): a Longitudinal Single-Center Study.

May 28, 2019 By Manish Butte

Clinical and Laboratory Features of 184 Italian Pediatric Patients Affected with Selective IgA Deficiency (SIgAD): a Longitudinal Single-Center Study.

J Clin Immunol. 2019 May 25;:

Authors: Lougaris V, Sorlini A, Monfredini C, Ingrasciotta G, Caravaggio A, Lorenzini T, Baronio M, Cattalini M, Meini A, Ruggeri L, Salpietro A, Pilotta A, Grazzani L, Prandi E, Felappi B, Gualdi G, Fabiano A, Fuoti M, Ravelli A, Villanacci V, Soresina A, Badolato R, Plebani A

Abstract
PURPOSE: Selective IgA deficiency (SIgAD) is the most common humoral primary immunodeficiency. Long-term follow-up data in large cohort of pediatric patients are scarce.
METHODS: We report on a single-center cohort of 184 pediatric patients affected with selective IgA deficiency and describe the characteristics at diagnosis and during follow-up.
RESULTS: Respiratory infections were the most common clinical finding leading to the initial diagnosis (62%). Positive family history for antibody deficiencies (selective IgA deficiency, common variable immunodeficiency) led to SIgAD diagnosis in 16% of cases. During follow-up, while the incidence of respiratory infections was not particularly high, gastrointestinal symptoms were reported in 27% of patients. Allergic manifestations were found in 23% at diagnosis and an additional 16% of patients during follow-up, leading to a prevalence of atopy of 39% among SIgAD patients. Autoimmune manifestations, excluding celiac disease, were found in 9% of affected patients during follow-up. Celiac disease was found in a high prevalence (14%). Increase of serum IgA levels to partial deficiency (9%) and normal serum levels for age (4%) was observed during follow-up. A small percentage of patients (2%) progressed to common variable immunodeficiency (CVID).
CONCLUSIONS: In conclusion, this is the first study to describe a large single-center pediatric cohort of patients affected with SIgAD, revealing that overall most patients do well with regard to infections. Many develop CD, at a rate much higher than the general population. A few normalize their IgA levels. A few progress to CVID. Thus, careful follow-up is suggested to diagnose and treat potential complications earlier for avoiding potential morbidities.

PMID: 31129864 [PubMed – as supplied by publisher]

Common Variable Immune Deficiency and Associated Complications.

May 28, 2019 By Manish Butte

Common Variable Immune Deficiency and Associated Complications.

Chest. 2019 May 22;:

Authors: Gupta S, Pattanaik D, Krishnaswamy G

Abstract
Common variable immunodeficiency (CVID) disorders refer to a relatively common primary immune deficiency group of diseases that present with infectious and inflammatory complications secondary to defects in antibody production and sometimes in cellular immunity. The disorder often presents in middle age or later with recurrent sinopulmonary infections, bronchiectasis or a plethora of noninfectious complications such as autoimmune disorders, granulomatous interstitial lung disease (GLILD), gastrointestinal diseases, malignancies (including lymphoma), and multisystem granulomatous disease resembling sarcoidosis. Infusion of immunoglobulin by intravenous (IVIG) or subcutaneous (SCIG) is the mainstay of therapy. Management of complications is often difficult as immune suppression may be necessary in these conditions, and entails the use of medications and biologicals which may further increase the risk for infections. Specifically, bronchiectasis, granulomatous lymphocytic interstitial lung disease, repeated sinopulmonary infections and malignancies are sequelae of antibody deficiency that may present to the pulmonologist. This review will provide an updated understanding of the molecular aspects, differential diagnosis, presentations and the management of CVID disorders.

PMID: 31128118 [PubMed – as supplied by publisher]

[Recurrent infections of the upper aerodigestive tract in patients with primary immunodeficiency].

May 24, 2019 By Manish Butte

[Recurrent infections of the upper aerodigestive tract in patients with primary immunodeficiency].

HNO. 2019 May 22;:

Authors: Ickrath P, Morbach H, Schwaneck EC, Gehrke T, Scherzad A, Hagen R, Hackenberg S

Abstract
BACKGROUND: Primary immunodeficiency is a rare disease of humoral and cellular immune defense, which can lead to severe and recurrent infections of different organs. The diagnosis of this disease is often difficult, and its early identification is necessary for adequate treatment and control.
OBJECTIVE: This study aimed to analyze ear, nose, and throat (ENT) infections in adults and children with a primary immunodeficiency. We attempted to characterize possible warning signs that should trigger an immunologic diagnostic workup.
MATERIALS AND METHODS: The current study comprised a retrospective case series of patients with primary immunodeficiencies. The type of immunodeficiency and the number of ENT infections were recorded.
RESULTS: A total of 85 Patients were included in the study. 56 patients (66%) had an acute exacerbation of chronic rhinosinusitis (n = 28), cervical lymphadenitis (n = 16), acute tonsillitis (n = 14), and acute otitis media (n = 6). Reporting detailed information about the frequencies and dates of infections was not possible, due to the retrospective nature of the analysis.
CONCLUSION: The prevalence of ENT infections in patients with a primary immunodeficiency is increased compared to the normal population. For the ENT specialist, these findings underline the necessity of including primary immunodeficiency in the differential diagnosis and initiating targeted diagnostic methods where indicated. Interdisciplinary collaboration with rheumatologists and immunologists is highly recommended, particularly for pediatric patients.

PMID: 31119330 [PubMed – as supplied by publisher]

A Critical View of Specific Antibody Deficiencies.

May 24, 2019 By Manish Butte

A Critical View of Specific Antibody Deficiencies.

Front Immunol. 2019;10:986

Authors: Sorensen RU

PMID: 31118939 [PubMed – in process]

Topical application of nebulized human IgG, IgA and IgAM in the lungs of rats and non-human primates.

May 24, 2019 By Manish Butte

Topical application of nebulized human IgG, IgA and IgAM in the lungs of rats and non-human primates.

Respir Res. 2019 May 22;20(1):99

Authors: Vonarburg C, Loetscher M, Spycher MO, Kropf A, Illi M, Salmon S, Roberts S, Steinfuehrer K, Campbell I, Koernig S, Bain J, Edler M, Baumann U, Miescher S, Metzger DW, Schaub A, Käsermann F, Zuercher AW

Abstract
BACKGROUND: Recurrent and persistent infections are known to affect airways of patients with Primary Immunodeficiency despite appropriate replacement immunoglobulin serum levels. Interestingly, patients with Chronic Obstructive Pulmonary Disease or with non-CF bronchiectasis also show similar susceptibility to such infections. This may be due to the limited availability of immunoglobulins from the systemic circulation in the conductive airways, resulting in local immunodeficiency. Topical application of nebulized plasma-derived immunoglobulins may represent a means to address this deficiency. In this study, we assessed the feasibility of nebulizing plasma-derived immunoglobulins and delivering them into the airways of rats and non-human primates.
METHODS: Distinct human plasma-derived immunoglobulin isotype preparations were nebulized with an investigational eFlow® nebulizer and analyzed in vitro or deposited into animals. Biochemical and immunohistological analysis of nebulized immunoglobulins were then performed. Lastly, efficacy of topically applied human plasma-derived immunoglobulins was assessed in an acute Streptococcus pneumoniae respiratory infection in mice.
RESULTS: Characteristics of the resulting aerosols were comparable between preparations, even when using solutions with elevated viscosity. Neither the structural integrity nor the biological function of nebulized immunoglobulins were compromised by the nebulization process. In animal studies, immunoglobulins levels were assessed in plasma, broncho-alveolar lavages (BAL) and on lung sections of rats and non-human primates in samples collected up to 72 h following application. Nebulized immunoglobulins were detectable over 48 h in the BAL samples and up to 72 h on lung sections. Immunoglobulins recovered from BAL fluid up to 24 h after inhalation remained structurally and functionally intact. Importantly, topical application of human plasma-derived immunoglobulin G into the airways of mice offered significant protection against acute pneumococcal pneumonia.
CONCLUSION: Taken together our data demonstrate the feasibility of topically applying plasma-derived immunoglobulins into the lungs using a nebulized liquid formulation. Moreover, topically administered human plasma-derived immunoglobulins prevented acute respiratory infection.

PMID: 31118031 [PubMed – in process]

Clinical Manifestations, Immunological Characteristics and Genetic Analysis of Patients with Hyper-Immunoglobulin M Syndrome in Iran.

May 23, 2019 By Manish Butte

Clinical Manifestations, Immunological Characteristics and Genetic Analysis of Patients with Hyper-Immunoglobulin M Syndrome in Iran.

Int Arch Allergy Immunol. 2019 May 22;:1-12

Authors: Tafakori Delbari M, Cheraghi T, Yazdani R, Fekrvand S, Delavari S, Azizi G, Chavoshzadeh Z, Mahdaviani SA, Ahanchian H, Khoshkhui M, Behmanesh F, Aleyasin S, Esmaeilzadeh H, Jabbari-Azad F, Fallahpour M, Zamani M, Madani SP, Moazzami B, Habibi S, Rezaei A, Lotfalikhani A, Movahed M, Shariat M, Kalantari A, Babaei D, Darabi M, Parvaneh N, Rezaei N, Abolhassani H, Aghamohammadi A

Abstract
BACKGROUND: Hyper-immunoglobulin M (HIGM) syndrome is a rare heterogeneous group of primary immunodeficiency disorders characterized by low or absent serum levels of IgG and IgA along with normal or elevated serum levels of IgM.
METHODS: Clinical and immunological data were collected from the 75 patients’ medical records diagnosed in Children’s Medical Center affiliated to Tehran University Medical Sciences and other Universities of Medical Sciences in Iran. Among 75 selected patients, 48 patients (64%) were analyzed genetically using targeted and whole-exome sequencing.
RESULTS: The ratio of male to female was 2.9:1. The median age at the onset of the disease, time of diagnosis, and diagnostic delay were 10.5, 50, and 24 months, respectively. Pneumonia and lower respiratory tract infections (61.3%) were the most common complications. Responsible genes were identified in 35 patients (72.9%) out 48 genetically analyzed patients. Cluster of differentiation 40 ligand gene was the most mutated gene observed in 24 patients (68.5%) followed by activation-induced cytidine deaminase gene in 7 patients, lipopolysaccharide-responsive and beige-like anchor (1 patient), nuclear factor-kappa-B essential modulator (1 patient), phosphoinositide-3-kinase regulatory subunit 1 (1 patient), and nuclear factor kappa B subunit 1 (1 patient) genes. Nineteen (25.3%) patients died during the study period, and pneumonia was the major cause of death occurred in 6 (31.6%) patients.
CONCLUSION: Physicians in our country should carefully pay attention to respiratory tract infections and pneumonia, particularly in patients with a positive family history. Further investigations are required for detection of new genes and pathways resulting in HIGM phenotype.

PMID: 31117086 [PubMed – as supplied by publisher]

Shared decision making: Does a physician’s decision-making style affect patient participation in treatment choices for primary immunodeficiency?

May 23, 2019 By Manish Butte

Shared decision making: Does a physician’s decision-making style affect patient participation in treatment choices for primary immunodeficiency?

J Eval Clin Pract. 2019 May 22;:

Authors: Lamb CC, Wang Y, Lyytinen K

Abstract
Overall health care spending in the United States is equivalent to more than 15% of GDP, yet outcomes rank below the top 25 in most quality categories when compared with other Organization for Economic Cooperation and Development (OECD) countries. The majority of spending is consumed by small patient populations with chronic diseases. Experts believe increased patient-physician shared decision making (SDM) should result in better overall longitudinal care but understanding the physician’s role in facilitating SDM is limited. Structural equation modelling was applied to results of a 2016 questionnaire-based survey of 330 US physicians who treat approximately 55% of primary immune deficiency requiring immune globulin therapy; it tested the relationship between slow/rational vs fast/intuitive decision-making styles and SDM as mediated by patient-centric care and moderated by physician’s trust in the patient. The results showed a statistically significant relationship between slow/rational decision making and SDM. The results also suggest differences related to age, gender, education, and race but no differences related to trust.

PMID: 31115958 [PubMed – as supplied by publisher]

CARMIL2 Deficiency Presenting as Very Early Onset Inflammatory Bowel Disease.

May 23, 2019 By Manish Butte

CARMIL2 Deficiency Presenting as Very Early Onset Inflammatory Bowel Disease.

Inflamm Bowel Dis. 2019 May 22;:

Authors: Magg T, Shcherbina A, Arslan D, Desai MM, Wall S, Mitsialis V, Conca R, Unal E, Karacabey N, Mukhina A, Rodina Y, Taur PD, Illig D, Marquardt B, Hollizeck S, Jeske T, Gothe F, Schober T, Rohlfs M, Koletzko S, Lurz E, Muise AM, Snapper SB, Hauck F, Klein C, Kotlarz D

Abstract
BACKGROUND: Children with very early onset inflammatory bowel diseases (VEO-IBD) often have a refractory and severe disease course. A significant number of described VEO-IBD-causing monogenic disorders can be attributed to defects in immune-related genes. The diagnosis of the underlying primary immunodeficiency (PID) often has critical implications for the treatment of patients with IBD-like phenotypes.
METHODS: To identify the molecular etiology in 5 patients from 3 unrelated kindred with IBD-like symptoms, we conducted whole exome sequencing. Immune workup confirmed an underlying PID.
RESULTS: Whole exome sequencing revealed 3 novel CARMIL2 loss-of-function mutations in our patients. Immunophenotyping of peripheral blood mononuclear cells showed reduction of regulatory and effector memory T cells and impaired B cell class switching. The T cell proliferation and activation assays confirmed defective responses to CD28 costimulation, consistent with CARMIL2 deficiency.
CONCLUSION: Our study highlights that human CARMIL2 deficiency can manifest with IBD-like symptoms. This example illustrates that early diagnosis of underlying PID is crucial for the treatment and prognosis of children with VEO-IBD.

PMID: 31115454 [PubMed – as supplied by publisher]

A novel Bruton tyrosine kinase gene variation was found in an adult with X-linked agammaglobulinemia during blood cross-matching prior to surgical operation.

May 23, 2019 By Manish Butte

A novel Bruton tyrosine kinase gene variation was found in an adult with X-linked agammaglobulinemia during blood cross-matching prior to surgical operation.

Transfus Med. 2019 May 22;:

Authors: Wang N, Tian Y, Jia S, Shao L, Yu W, Fang M

Abstract
AIMS/OBJECTIVES: To investigate the underlying molecular mechanism of the patient’s ABO typing discrepancy.
BACKGROUND: ABO typing discrepancy was frequently seen in patients due to different causes. In this study, ABO typing discrepancy was found in a 24-year-old man with arthralgia, whose forward ABO grouping was O and reverse ABO grouping was AB. Primary immunodeficiency disease was speculated in this patient, especially X-linked agammaglobulinemia (XLA).
METHODS: Immunoglobulins of all isotypes were detected using a specific protein analyser. Lymphocyte subgroups were analysed by flow cytometry. All 19 exons and boundaries of BTK gene were amplified by polymerase chain reaction (PCR), and all PCR products were sequenced by a DNA analyser. BTK protein in the leukocytes and platelets was detected by Western blot.
RESULTS: No B lymphocytes could be detected in the peripheral blood of the patient. A novel BTK gene variation, c.817G>T, in the exon 9 of BTK gene was discovered. No BTK protein expression could be detected in the leukocytes and platelets of the patient.
CONCLUSIONS: XLA could be occasionally discovered by ABO typing discrepancy in some cases because of the deficiency of reciprocal IgM anti-A and/or anti-B antibodies in the serum of the patient. Humoral immunodeficiency is one of the causes of ABO typing discrepancy.

PMID: 31115091 [PubMed – as supplied by publisher]