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1.
Erez Rechavi Atar Lev Eran Eyal Ortal Barel Nitzan Kol Sarit Farage Barhom Ben Pode-Shakked Yair Anikster Raz Somech Amos J. Simon 《Journal of clinical immunology》2016,36(8):801-809
Purpose
Immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome is an extremely rare autosomal recessive disease. The immune phenotype is characterized by hypogammaglobulinemia in the presence of B cells. T cell lymphopenia also develops in some patients. We sought to further investigate the immune defect in an ICF patient with a novel missense mutation in DNMT3B and a severe phenotype.Methods
Patient lymphocytes were examined for subset counts, immunoglobulin levels, T and B cell de novo production (via excision circles) and receptor repertoire diversity. Mutated DNMT3B protein structure was modeled to assess the effect of a mutation located outside of the catalytic region on protein function.Results
A novel homozygous missense mutation, Ala585Thr, was found in DNMT3B. The patient had decreased B cell counts with hypogammaglobulinemia, and normal T cell counts. CD4+ T cells decreased over time, leading to an inversion of the CD4+ to CD8+ ratio. Excision circle copy numbers were normal, signifying normal de novo lymphocyte production, but the ratio between naïve and total B cells was low, indicating decreased in vivo B cell replication. T and B cell receptor repertoires displayed normal diversity. Computerized modeling of the mutated Ala585 residue suggested reduced thermostability, possibly affecting the enzyme kinetics.Conclusions
Our results highlight the existence of a T cell defect that develops over time in ICF patient, in addition to the known B cell dysfunction. With intravenous immunoglobulin (IVIG) treatment ameliorating the B cell defect, the extent of CD4+ lymphopenia may determine the severity of ICF immunodeficiency.2.
3.
Background
The CD5 protein antagonizes phosphorylation events downstream of T cell receptor (TCR) engagement to decrease T cell responsiveness. CD5-negative T cell clones respond preferentially over their CD5+ counterparts against cells with low human histocompatibility-linked leukocyte antigen (HLA) levels. In human immunodeficiency virus type 1 (HIV-1) infection, CD5-CD8+ T cells increase in prevalence with disease progression.Methods
To investigate potential causes of this expansion of CD5-CD8+ T cells in HIV-1 infection, we compared CD5 expression on CD8+ T cells reactive against HIV-1 peptides, common viral peptides and a self peptide that together span a broad range of TCR avidities in the context of the common HLA-A2 class I restriction molecule. Following stimulation, CD5 expression on peptide-specific CD8+ T cells was assessed by flow cytometry.Results
In healthy controls, there was no significant difference in the CD5+ percentage of CD8+ T cells specific for common viral peptides, but a lower percentage of those responding against a common self peptide expressed CD5. The same relationship occurred in HIV-infected individuals, however, a lower percentage of HIV peptide-specific CD8+ T cells than other viral peptide-specific CD8+ T cells expressed CD5. In terms of overall CD5 expression level at the peptide-specific responder population level, HIV-specific CD8+ T cells resembled those responsive against the self peptide, despite much higher avidity TCR/HLA/peptide interactions.Conclusions
This deficit in CD5 expression selective for HIV-specific CD8+ T cells is consistent with in vivo adaptation to low avidity HIV peptide variants and has potential consequences for CD8+ T cell expansion, cross-reactivity and autoreactivity.4.
5.
Takehiro Takashima Miko Okamura Tzu-wen Yeh Tsubasa Okano Motoi Yamashita Keisuke Tanaka Akihiro Hoshino Noriko Mitsuiki Masatoshi Takagi Eiichi Ishii Kohsuke Imai Hirokazu Kanegane Tomohiro Morio 《Journal of clinical immunology》2017,37(5):486-495
Purpose
Primary immunodeficiency diseases (PIDDs) are rare inherited diseases that impair the human immune system. We established a multicolor flow cytometric assay to comprehensively evaluate the immune status and immunological characteristics of patients with PIDDs.Methods
Fifty-nine normal controls and 75 patients with PIDDs, including X-linked severe combined immunodeficiency (X-SCID), X-linked agammaglobulinemia (XLA), X-linked hyper IgM syndrome (X-HIGM), ataxia telangiectasia (AT), Wiskott-Aldrich syndrome (WAS), hyper IgE syndrome (HIES), and chronic mucocutaneous candidiasis disease (CMCD), were enrolled in this study. Immunophenotyes were evaluated by multicolor flow cytometry using seven different panels that allowed the detection of major leukocyte populations in peripheral blood.Results
Multicolor flow cytometry revealed distinct leukocyte populations and immunological features of patients with X-SCID, XLA, X-HIGM, AT, WAS, HIES, and CMCD.Conclusions
Immunophenotyping by multicolor flow cytometry is useful to evaluate immune status and contributes to the diagnosis and management of patients with PIDDs.6.
Yiwa Suksawat Achara Sathienkijkanchai Jittima Veskitkul Orathai Jirapongsananuruk Nualanong Visitsunthorn Pakit Vichyanond Punchama Pacharn 《Journal of clinical immunology》2017,37(4):375-382
Purpose
Patients with 22q11.2 deletion syndrome have a variable decrease in immunological parameters, especially regarding T cell counts. The aim of this study was to investigate immunological change over time and factors associated with immunological recovery among patients with 22q11.2 deletion syndrome.Methods
Patients with 22q11.2 deletion syndrome diagnosed by fluorescence in situ hybridization (FISH) were studied. Immunological parameters were evaluated every 6 months until patients returned to normal. Infection and vaccination histories were recorded and analyzed, and Kaplan-Meier survival curves were plotted to describe resolution of immunodeficiency.Results
Forty-nine patients with an age range of 4 to 222 months were included. Twenty-five (51%) patients were female. In hypocalcemia, the odds ratio for CD4 lymphopenia was 17.03 (95%CI 1.82–159.23; p value = 0.01). Thirty patients (61.2%) exhibited decreased CD4+ T cell numbers, which returned to normal level in 18 (60%) patients. Median age of CD4+ T cell resolution was 2.5 years. T cell functions were abnormal in three patients. T cell functions returned to normal in all patients at a median age of 1.1 years. Six patients (13.5%) had abnormal serum immunoglobulin levels, with levels improving in four patients at 1.4 years of age. The most common infection was pneumonia (69.4%). BCG vaccination was administered in 47 of 49 patients at birth. Among 32 patients who had T cell defect, one patient developed BCGitis and one developed disseminated BCG.Conclusion
Immunodeficiencies identified among patients with 22q11.2 deletion syndrome were T cell defect (65.3%) and decreased immunoglobulin levels (12.2%). Median age of CD4 resolution was 2.5 years.7.
Ruud W. J. Meijers Katarzyna Dzierzanowska-Fangrat Magdalena Zborowska Iwona Solarska Dennis Tielemans Bob A. C. van Turnhout Gertjan Driessen Mirjam van der Burg Jacques J. M. van Dongen Krystyna H. Chrzanowska Anton W. Langerak 《Journal of clinical immunology》2017,37(2):133-142
Purpose
The Nijmegen breakage syndrome (NBS) is an inherited genetic disorder characterized by a typical facial appearance, microcephaly, growth retardation, immunodeficiency, and a strong predisposition to malignancies, especially of lymphoid origin. NBS patients have a mutation in the NBN gene which involves the repair of DNA double-strand breaks (DSBs). Here we studied the peripheral T cell compartment of NBS patients with a focus on immunological senescence.Methods
The absolute numbers and frequencies of the different T cell subsets were determined in NBS patients from young age till adulthood and compared to age-matched healthy individuals (HI). In addition, we determined the expression of senescent T cell markers and the signal joint T cell receptor excision circles (sjTRECs) content.Results
Our results demonstrate that NBS patients have reduced T cell numbers. NBS patients showed lower numbers of αβ+ T cells, but normal γδ+ T cell numbers compared to HI. Concerning the αβ+ T cells, both CD4+ as well as CD8+ T cells were excessively reduced in numbers compared to aged-matched HI. In addition, NBS patients showed higher frequencies of the more differentiated T cells expressing the senescent cell marker CD57 and did not express co-stimulatory molecule CD28. These effects were already present in the youngest age group. Furthermore, NBS patients showed lower sjTREC content in their T cells possibly indicative of a lower thymic output.Conclusions
We conclude that circulating T cells from NBS patients show signs of a senescent phenotype which is already present from young age on and which might explain their T cell immune deficiency.8.
Bianca Tesi Peter Priftakis Fredrik Lindgren Samuel C. C. Chiang Nikolaos Kartalis Alexandra Löfstedt Esther Lörinc Jan-Inge Henter Jacek Winiarski Yenan T. Bryceson Marie Meeths 《Journal of clinical immunology》2016,36(5):480-489
Purpose
Autosomal recessive mutations in LRBA, encoding for LPS-responsive beige-like anchor protein, were described in patients with a common variable immunodeficiency (CVID)-like disease characterized by hypogammaglobulinemia, autoimmune cytopenias, and enteropathy. Here, we detail the clinical, immunological, and genetic features of a patient with severe autoimmune manifestations.Methods
Whole exome sequencing was performed to establish a molecular diagnosis. Evaluation of lymphocyte subsets was performed for immunological characterization. Medical files were reviewed to collect clinical and immunological data.Results
A 7-year-old boy, born to consanguineous parents, presented with autoimmune hemolytic anemia, hepatosplenomegaly, autoimmune thyroiditis, and severe autoimmune gastrointestinal manifestations. Immunological investigations revealed low immunoglobulin levels and low numbers of B and NK cells. Treatment included immunoglobulin replacement and immunosuppressive therapy. Seven years after disease onset, the patient developed severe neurological symptoms resembling acute disseminated encephalomyelitis, prompting allogeneic hematopoietic stem cell transplantation (HSCT) with the HLA-identical mother as donor. Whole exome sequencing of the patient uncovered a homozygous 1 bp deletion in LRBA (c.7162delA:p.T2388Pfs*7). Importantly, during 2 years of follow-up post-HSCT, marked clinical improvement and recovery of immune function was observed.Conclusions
Our data suggest a beneficial effect of HSCT in patients with LRBA deficiency.9.
Yuliya V. Perfilyeva Nurshat Abdolla Yekaterina O. Ostapchuk Raikhan Tleulieva Vladimir C. Krasnoshtanov Nikolai N. Belyaev 《Inflammation research》2017,66(8):711-724
Objective
Myeloid-derived suppressor cells (MDSCs) are important negative regulators of immune processes in cancer and other pathological conditions. We suggested that MDSCs play a key role in pathogenesis of chronic inflammation, which precedes and, to a certain extent, induces carcinogenesis. The present study aimed at investigation of MDSCs arising during chronic inflammation and light-at-night (LN)-induced stress, which is shown to accelerate chronic diseases.Subjects
67 CD-1 mice and in vitro MDSC cultures.Treatment
Adjuvant arthritis was induced by a subdermal injection of complete Freund’s adjuvant. LN was induced by illumination of 750 lx at night.Methods
Flow cytometry for evaluation of cell phenotypes and MTT standard test for cell proliferation were used.Results
Increased levels of splenic CD11b+Ly6Ghigh and CD11b+CD49d+ myeloid cells possessing suppressive potential in mice with adjuvant arthritis are shown. LN amplifies the process of CD11b+Ly6Ghigh expansion in mice with adjuvant arthritis. Expression of CD62L and CD195 is elevated on the myeloid cells during exposure to LN.Conclusions
Our study raises the possibility that CD11b+Ly6Ghigh and CD11b+CD49d+ MDSCs play an important role in the induction of immunosuppressive environment typical for chronic inflammation. Also, LN can affect immune responses during chronic inflammation through recruitment of MDSCs from the bone marrow.10.
M. Vajpayee S. Kaushik V. Sreenivas K. Mojumdar S. Mendiratta N. K. Chauhan 《European journal of clinical microbiology & infectious diseases》2009,28(1):69-73
Objectives
The correlation of immune activation with CD4+ depletion and HIV-1 disease progression has been evidenced by several studies involving mainly clade B virus. However, this needs to be investigated in developing countries such as India predominately infected with clade C virus.Materials and methods
In a cross-sectional study of 68 antiretroviral treatment naïve, HIV-1 infected Indian patients, we studied the association between CD4+ T cells, plasma HIV-1 RNA levels, and immune activation markers using unadjusted and adjusted correlative analyses.Results
Significant negative correlations of higher magnitude were observed between the CD4+ T cell percentages and plasma HIV-1 RNA levels in the study population when adjusted for the effects of immune activation markers. However, the negative association of CD4+ T cells with immune activation markers remained unaffected when controlled for the effects of plasma HIV-1 RNA levels.Conclusions
Our results support the important role of immune activation in CD4+ T cell depletion and disease progression during untreated HIV-1 infection.11.
Joud Hajjar Danielle Guffey Charles G. Minard Jordan S. Orange 《Journal of clinical immunology》2017,37(2):153-165
Introduction
Patients with primary immunodeficiency (PID) often report fatigue, yet this symptom has not been studied in PID. Fatigue affects 6–7.5% of healthy adults. The goal of this study is to estimate the prevalence of fatigue in patients with PID and investigate its associated factors.Methods
We analyzed 2537 PID patients registered in USIDNET to determine responses to the field “fatigue” in the core registry form. Demographics, immune phenotypes, and comorbid conditions were compared between fatigued and non-fatigued patients to identify relevant associations and potential drivers. A focused analysis was performed for patients with predominantly antibody deficiency disorders (PADs).Results
Fatigue was reported in 25.9% (95% CI 23.7–28.3) of PAD patients, compared to 6.4% (95% CI 4.9–8.2) of non-PAD. Patients with common variable immunodeficiency (CVID) had the highest prevalence of fatigue (p < 0.001) among all PID diagnoses. Other factors that were associated with a higher rate of fatigue among PAD patients included female sex, higher BMI, depression, bronchiectasis, and autoimmunity. Additionally, fatigued PAD patients had lower absolute lymphocyte, CD3, CD4, and CD8 counts compared to non-fatigued patients.Conclusion
Our findings suggest that fatigue is overrepresented in PAD patients. Prospective studies to estimate prevalence, risk factors, and fatigue etiology in PID are warranted, so therapeutic interventions can be considered.12.
Beatriz T. Costa-Carvalho Kathleen E. Sullivan Patrícia M. Fontes Fernanda Aimé-Nobre Isabela G. S. Gonzales Elaine S. Lima Celso Granato Maria Isabel de Moraes-Pinto 《Journal of clinical immunology》2018,38(5):628-634
Purpose
Poliovirus has been nearly eliminated as part of a world-wide effort to immunize and contain circulating wild-type polio. Nevertheless, poliovirus has been detected in water supplies and represents a threat to patients with humoral immunodeficiencies where infection can be fatal. To define the risk, we analyzed antibodies to poliovirus 1, 2, and 3 in serum samples collected over a year from patients with primary immunodeficiency diseases (PID) on regular intravenous immunoglobulin (IVIG) replacement.Methods
Twenty-one patients on regular IVIG replacement therapy were evaluated: Twelve patients with common variable immune deficiency (CVID), six with X-linked agammaglobulinemia (XLA), and three with hyper IgM syndrome (HIGM). Over 1 year, four blood samples were collected from each of these patients immediately before immunoglobulin infusion. One sample of IVIG administered to each patient in the month before blood collection was also evaluated. Poliovirus antibodies were quantified by seroneutralization assay.Results
All IVIG samples had detectable antibodies to the three poliovirus serotypes. Despite that, only 52.4, 61.9, and 19.0% of patients showed protective antibody titers for poliovirus 1, 2, and 3, respectively. Only two patients (9.5%) had protective antibodies for the three poliovirus serotypes on all samples. Most patients were therefore susceptible to all three poliovirus serotypes.Conclusions
This study demonstrates the need for ongoing vigilance regarding exposure of patients with PID to poliovirus in the community.13.
Wenjun Mou Wei Han Xiaoli Ma Xiaolin Wang Hong Qin Wen Zhao Xiaoya Ren Xi Chen Wei Yang Haiyan Cheng Xisi Wang Hui Zhang Xin Ni Huanmin Wang Jingang Gui 《BMC immunology》2017,18(1):36
Background
Previous studies have shown that γδ TFH cells are capable of modulating antibody production in immunized and infected mouse model. In recent studies, human γδ TFH cells are shown to contribute to the activation of humoral immunity and promote the maturation of B cells. However, little information is available on their involvement in neuroblastoma (NB) pathogenesis.Results
In the present study, the frequency of γδ TFH cells in 74 NB patients was significantly higher compared with that in 60 healthy controls. Moreover, most γδ TFH cells in NB patients had a naive phenotype with up-regulation of CD25, CD69, HLA-DR and CD40L and down-regulation of ICOS. Importantly, γδ TFH cells in NB patients produced more IL-4 and IL-10 than those in healthy controls. Furthermore, serum total IgG level was significantly increased in NB patients compared with healthy controls. The expression of CD23 on B cells was up-regulated while CD80 expression was significantly down-regulated in NB patients. Further analysis of B cell compartment showed that the frequency of CD19+CD27hi plasma cells was enhanced in NB patients. Spearman’s correlation analysis revealed that the frequency of γδ TFH cells was positively correlated to serum total IgG level and CD19+CD27hi plasma cells in NB patients, but negatively correlated to CD19+ B cells.Conclusions
We concluded that γδ TFH cells might promote B cell maturation and antibody production in NB patients.14.
Mark Ballow Paul J. Pinciaro Timothy Craig Gary Kleiner James Moy Hans D. Ochs John Sleasman William Smits 《Journal of clinical immunology》2016,36(6):583-589
Purpose
The previous studies with Flebogamma® 5 % DIF intravenous immunoglobulin (IVIG) contained insufficient numbers of pediatric subjects to fully warrant a pediatric indication by the FDA. The objective of this study was to evaluate the efficacy, safety, and pharmacokinetics of Flebogamma® 5 % DIF for replacement therapy in children (age 2–16) with primary immunodeficiency diseases (PIDD).Methods
IVIG was administered at eight clinical sites to 24 subjects with well-defined PIDD at a dose of 300–800 mg/kg every 21–28 days for 12 months. The pharmacokinetics endpoint in this study was the dose-adjusted increment of the serum IgG trough levels.Results
The calculated serious bacterial infection rate was 0.05/subject/year. The incidence of adverse events considered potentially related to IVIG during or within 72 h after completing an infusion was within the FDA guidance threshold of <40 % at each time point. Dose-adjusted incremental IgG levels remained approximately equal to or slightly greater than pre-study IgG levels (between 800 and 1000 mg/dL throughout) when the subjects were treated with IVIG therapy other than Flebogamma® DIF 5 % indicating no evidence of a different pharmacokinetic profile in this pediatric population if compared to those profiles in previous Flebogamma studies in predominately adult populations.Conclusions
Flebogamma® 5 % DIF is efficacious and safe, has adequate pharmacokinetic properties, is well-tolerated, and maintains the profile of Flebogamma® 5 % for the treatment of children with primary humoral immunodeficiency diseases.15.
Masayuki Hori Takahiro Yasumi Saeko Shimodera Hirofumi Shibata Eitaro Hiejima Hirotsugu Oda Kazushi Izawa Tomoki Kawai Masataka Ishimura Naoko Nakano Ryutaro Shirakawa Ryuta Nishikomori Hidetoshi Takada Satoshi Morita Hisanori Horiuchi Osamu Ohara Eiichi Ishii Toshio Heike 《Journal of clinical immunology》2017,37(1):92-99
Purpose
Familial hemophagocytic lymphohistiocytosis type 3 (FHL3) is a genetic disorder that results in immune dysregulation. It requires prompt and accurate diagnosis. A natural killer (NK) cell degranulation assay is often used to screen for FHL3 patients. However, we recently encountered two cases of late-onset FHL3 carrying novel UNC13D missense mutations: in these cases, the degranulation assays using freshly isolated and interleukin (IL)-2-activated NK cells yielded contradictory results. Since the defective degranulation of CD57+ cytotoxic T lymphocytes (CTLs) in these cases was helpful for making the diagnosis, we assessed whether the CD57+ CTL degranulation assay more effectively identified FHL3 patients than the NK cell assays.Methods
Forty additional patients with hemophagocytic lymphohistiocytosis were prospectively screened for FHL3 by measuring the perforin expression in NK cells and the expression of Munc13-4, syntaxin-11, and Munc18-2 in platelets and by performing NK cell and CTL degranulation assays. The results were confirmed by genetic analysis.Results
The freshly isolated NK cell degranulation assay detected FHL3 patients with high sensitivity (100%) but low specificity (71%). The IL-2-stimulated NK cell assay had improved specificity, but 3 out of the 31 non-FHL3 patients still showed degranulation below the threshold level. The CD57+ CTL degranulation assay identified FHL3 patients with high sensitivity and specificity (both 100%).Conclusions
The CD57+ CTL degranulation assay more effectively identified FHL3 patients than the NK cell-based assays.16.
Clemens Wirsum Cornelia Glaser Sylvia Gutenberger Baerbel Keller Susanne Unger Reinhard E. Voll Werner Vach Thomas Ness Klaus Warnatz 《Journal of clinical immunology》2016,36(4):406-412
Purpose
The aim of this study was to identify characteristics of hypogammaglobulinemia secondary to glucocorticoid therapy and their value in the differential diagnosis to primary forms of antibody deficiency.Methods
We investigated prevalence and character of hypogammaglobulinemia in a cohort of 36 patients with giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) on glucocorticoid therapy in comparison to a gender- and age-matched cohort of hospital controls. We therefore determined serum immunoglobulin levels as well as B- and T cell-subsets in the peripheral blood of all participants. In addition, prior serum immunoglobulin levels and clinical data of the GCA and PMR patients were extracted from the electronic patient data-base.Results
21/36 GCA/PMR patients on glucocorticoid treatment developed antibody deficiency. In 19 patients this included IgG and in 13 patients IgG was the only affected isotype. The reduction of IgG was persistent in nearly 50 % of these patients during the observed period. GCA/PMR patients had reduced circulating naive and transitional B cells (p = 0.0043 and p = 0.0002 respectively) while IgM, IgG and IgA memory B cells were preserved. Amongst T-cell subsets, we found a reduction of CD4 memory T cells (p < 0.0001), CD4 regulatory T cells (p = 0.0002) and few CD8 memory T-cell subtypes.Conclusion
Persistent humoral immunodeficiency occurs in about a quarter of GCA/PMR patients under glucocorticoid therapy. Because most patients have isolated IgG deficiency, preserved IgA production and class-switched memory B cells, by these markers this form of secondary hypogammaglobulinemia can be clearly distinguished from common variable immunodeficiency (CVID).17.
Boris Bienvenu Grégoire Cozon Yves Mataix Dominique Lachaud Antoine Alix Cyrille Hoarau Daniel Antier Eric Hachulla Sylvie Brice Jean-François Viallard Stéphanie Tamisier Anne-Laure Fauchais Françoise Renon-Carron Pierre Clerson Yann Fardini Jean-Charles Crave Pierre Miossec 《Journal of clinical immunology》2018,38(4):503-512
Purpose
Subcutaneous immunoglobulin replacement therapy (IgRT) may be administered once a week with a pump or every other day with a syringe (rapid push). The objective of the study was to compare the impact of pump and rapid push infusions on patient’s life quality index (LQI).Methods
This study was a randomized, crossover, multicenter, non-inferiority trial conducted in adults with primary immunodeficiency (PID) accustomed to weekly infusions at home by pump. Patients used pump or rapid push for 3 months each according to the randomized sequence. Main criterion was PID-LQI factor I (treatment interference). Non-inferiority ratio was set at 90%.Results
Thirty patients entered the study; 28 completed the two periods. IgRT exposure was similar during each period. At the end of each period, mean LQI factor 1 was 87.0 (IC95% [80.3; 94.3]) and 77.80 (IC95% [71.5; 84.7]) for pump and rapid push, respectively. There was a slightly larger effect of rapid push on treatment interference than with pump so that the primary endpoint could not be met. No difference was found on other LQI components, satisfaction (TSQM), or quality of life (SF36v2). Eight patients declared to prefer rapid push while 19 others preferred pump. Of rapid push infusions, 67.2% led to local reactions vs 71.8% of pump infusions (p?=?0.11) illustrating its good tolerance. Rapid push and pump infusions achieved similar trough IgG levels with similar incidence of infections. Rapid push saved 70% of administration cost when compared to pump.Conclusions
Since IgRT is a lifelong treatment in PID patients, individualization of treatment is of paramount importance. Rapid push is a new administration method in the physician’s armamentarium which is preferred by some patients and is cost-effective.ClinicalTrials.gov Identifier
NCT02180763Clinical Implications
Self-administration of small volumes of immunoglobulins at home, every other day, using a syringe (rapid push) is a cost-effective alternative to administration of larger volumes by pump once a week.Capsule Summary
This study compared subcutaneous infusions of immunoglobulins either weekly via a pump or every other day via a syringe (rapid push). Rapid push is preferred by some patients and is cost-effective, therefore completing a physician’s armamentarium.18.
19.
Rajiv Mallick Stephen Jolles Hirokazu Kanegane Dominique Agbor-Tarh Mikhail Rojavin 《Journal of clinical immunology》2018,38(8):886-897