Abstract:
:Early detection of Primary Immunodeficiencies Disorders (PIDDs) is of paramount importance for effective treatment and disease management. Many PIDDs would be strong candidates for newborn screening (NBS) if robust screening methods could identify patients from dried blood spots (DBS) during the neonatal period. As majority of congenital PIDDs result in the reduction or absence of specific proteins, direct quantification of these target proteins represents an attractive potential screening tool. Unfortunately, detection is often limited by the extremely low protein concentrations in blood cells and limited blood volume present in DBS. We have recently developed a robust novel method for quantification of low abundance proteins in DBS for PIDDs using peptide immunoaffinity enrichment coupled to selected reaction monitoring (immuno-SRM). Here, we further generated a multiplexed Immuno-SRM panel for simultaneous screening of eight signature peptides representing five PIDD-specific and two cell-type specific proteins from DBS. In samples from 28 PIDD patients including two carriers, representing X-Linked Agammaglobulinemia (XLA), Wiskott-Aldrich Syndrome (WAS), X-Linked Chronic Granulomatous Disease (XL-CGD), DOCK8 Deficiency and ADA deficiency, peptides representing each disease are significantly reduced relative to normal controls and patient identification had excellent agreement with clinical and molecular diagnosis. Also included in the multiplex panel are cell specific markers for platelets (CD42) and Natural Killer Cells (CD56). In patients with WAS, CD42 levels were found to be significantly reduced consistent with characteristic thrombocytopenia. A patient with WAS analyzed before and after bone marrow transplant showed normalized WAS protein and platelet CD42 after treatment highlighting the ability of immuno-SRM to monitor the effects of PIDD treatment. The assay was readily reproduced in two separate laboratories with similar analytical performance and complete agreement in patient diagnosis demonstrating the effective standardized methods. A high-throughput Immuno-SRM method screens PIDD-specific peptides in a 2.5-min runtime meeting high volume NBS workflow requirements was also demonstrated in this report. This high-throughput method returned identical results to the standard Immuno-SRM PIDD panel. Immuno-SRM peptide analysis represents a robust potential clinical diagnostic for identifying and studying PIDD patients from easily collected and shipped DBS and supports a significant potential for early PIDD diagnosis through newborn screening.
journal_name
Front Immunoljournal_title
Frontiers in immunologyauthors
Collins CJ,Yi F,Dayuha R,Whiteaker JR,Ochs HD,Freeman A,Su HC,Paulovich AG,Segundo GRS,Torgerson T,Hahn SHdoi
10.3389/fimmu.2020.00464subject
Has Abstractpub_date
2020-04-01 00:00:00pages
464issn
1664-3224journal_volume
11pub_type
杂志文章abstract::Dendritic cells (DCs) are specialized antigen presenting cells that are exquisitely adapted to sense pathogens and induce the development of adaptive immune responses. They form a complex network of phenotypically and functionally distinct subsets. Within this network, individual DC subsets display highly specific rol...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2012.00026
更新日期:2012-02-27 00:00:00
abstract::Pulmonary tuberculosis (TB) is a difficult-to-eliminate disease. Although the Bacille Calmette-Guérin (BCG) vaccine against Mycobacterium tuberculosis (MTB) has been available for decades, its efficacy is variable and has lessened over time. Furthermore, the BCG vaccine no longer protects against newly emerged Beijing...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.01298
更新日期:2020-06-23 00:00:00
abstract::This review discusses the mechanisms and consequences of degradation of tryptophan (Trp) in the placenta, focusing mainly on the role of indoleamine 2,3-dioxygenase-1 (IDO1), one of three enzymes catalyzing the first step of the kynurenine pathway of Trp degradation. IDO1 has been implicated in regulation of feto-mate...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2014.00230
更新日期:2014-05-19 00:00:00
abstract::Invariant natural killer T (iNKT) cells produce copious amounts of cytokines in response to T-cell receptor (TCR) stimulation by recognizing antigens such as α-galactosylceramide (α-GalCer) presented on CD1d; thus, orchestrating other immune cells to fight against pathogen infection and tumors. Because of their abilit...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2018.02021
更新日期:2018-09-07 00:00:00
abstract::Anemia of inflammation (AI) is the second most prevalent anemia after iron deficiency anemia and results in persistent low blood erythrocytes and hemoglobin, fatigue, weakness, and early death. Anemia of inflammation is common in people with chronic inflammation, chronic infections, or sepsis. Although several studies...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.583550
更新日期:2020-10-06 00:00:00
abstract::Atopic dermatitis (AD) is a complex multifactorial inflammatory skin disease that affects ~280 million people worldwide. About 85% of AD cases begin in childhood, a significant portion of which can persist into adulthood. Moreover, a typical progression of children with AD to food allergy, asthma or allergic rhinitis ...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2018.02727
更新日期:2018-12-12 00:00:00
abstract::The Pediatric Acute Liver Failure (PALF) study is a multicenter, observational cohort study of infants and children diagnosed with this complex clinical syndrome. Outcomes in PALF reflect interactions among the child's clinical condition, response to supportive care, disease severity, potential for recovery, and, if n...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.610861
更新日期:2021-01-15 00:00:00
abstract::Enamel matrix derivatives (EMDs)-based periodontal tissue regenerative therapy is known to promote healing with minimal inflammatory response after periodontal surgery, i. e., it promotes wound healing with reduced pain and swelling. It has also been reported that macrophages stimulated with amelogenin, a major compon...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.00709
更新日期:2020-04-21 00:00:00
abstract::Anti-tumor immunity is limited by a number of factors including the lack of fully activated T-cells, insufficient antigenic stimulation and the immune-suppressive tumor microenvironment. We addressed these hurdles by developing a novel class of immunoconjugates, Antibody-Targeted Pathogen-derived Peptides (ATPPs), whi...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.01962
更新日期:2019-08-21 00:00:00
abstract::Chronic hepatitis C virus (HCV) infection disrupts immune functions, including that of cytotoxic CD8+ T-cells which are important mediators of immune response. While HCV cure aims to eliminate long term sequelae of infection, whether direct-acting antiviral (DAA) treatment results in immune reconstitution remains uncl...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.01926
更新日期:2019-08-13 00:00:00
abstract::Tuberculosis (TB) is a major health issue globally. Although typically the disease can be cured by chemotherapy in all age groups, and prevented in part in newborn by vaccination, general consensus exists that development of novel intervention measures requires better understanding of disease mechanisms. Human TB is c...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2014.00036
更新日期:2014-02-05 00:00:00
abstract::In the current quest for a complete cure for HIV/AIDS, highly sensitive HIV-1 latency detection methods are critical to verify full viral eradication. Until now, the in vitro quantitative viral outgrowth assays (qVOA) have been the gold standard for assessing latent HIV-1 viral burden. However, these assays have been ...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2018.00344
更新日期:2018-03-05 00:00:00
abstract::Fibroblastic reticular cells (FRCs) are the specialized lymphoid stromal cells initially identified as triggering T-cell recruitment and dynamic motion in secondary lymphoid organs. Interestingly, FRCs also display antigen presentation capacities and support lymphocyte survival. CXCR5+CD4+ follicular T cells are impor...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.559866
更新日期:2020-10-02 00:00:00
abstract::Two decades of clinical cancer research with dendritic cell (DC)-based vaccination have proved that this type of personalized medicine is safe and has the capacity to improve survival, but monotherapy is unlikely to cure the cancer. Designed to empower the patient's antitumor immunity, huge research efforts are set to...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2018.00394
更新日期:2018-03-01 00:00:00
abstract::The 5-year survival rate of primary anorectal malignant melanoma is less than 20%. Optimal treatment of this condition remains controversial regarding locally disease, and whether any preferential survival benefit arises from either abdominoperineal resection or wide local excision remains unknown. The majority of pat...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.00797
更新日期:2018-04-19 00:00:00
abstract::The Signaling Lymphocyte Activation Molecule Family (SLAMF) genes, which encode cell-surface receptors that modulate innate and adaptive immune responses, lay within a genomic region of human and mouse chromosome 1 that confers a predisposition for the development of systemic lupus erythematosus (SLE). Herein, we demo...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2013.00225
更新日期:2013-07-31 00:00:00
abstract::An efficient B cell immunity requires a dynamic equilibrium between positive and negative signals. In germinal centers (GCs), T follicular helper cells are supposed to be the positive regulator while T follicular regulatory (Tfr) cells were assigned to be the negative regulators. Indeed, Tfr cells are considered as a ...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2018.01792
更新日期:2018-08-13 00:00:00
abstract::CD24 expression on pro-B cells plays a role in B cell selection and development in the bone marrow. We previously detected higher CD24 expression and frequency within IgD+ naïve and memory B cells in patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) compared with age-matched healthy controls (H...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.02421
更新日期:2018-10-22 00:00:00
abstract::Endothelial cells are thought to play a central role in the pathogenesis of antiphospholipid syndrome (APS). Omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation has been shown to improve endothelial function in a number of diseases; thus, it could be of high clinical relevance in APS. The aim of this study w...
journal_title:Frontiers in immunology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.3389/fimmu.2018.00336
更新日期:2018-03-02 00:00:00
abstract::Pleural effusions, when benign, are attributed to cardiac events and suffusion of fluid within the pleural space. When malignant, lymphatic obstruction by tumor and failure to absorb constitutively produced fluid is the predominant formulation. The prevailing view has been challenged recently, namely that the lymphati...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.02027
更新日期:2020-09-04 00:00:00
abstract::Immune aging is best known for its immune defects that increase susceptibility to infections and reduce adaptive immune responses to vaccination. In parallel, the aged immune system is prone to autoimmune responses and many autoimmune diseases increase in incidence with age or are even preferentially encountered in th...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2013.00131
更新日期:2013-06-04 00:00:00
abstract::Epidemiological investigations have shown that smoking ameliorates ulcerative colitis (UC) but exacerbates Crohn's disease (CD), diseases that feature a Th2-mediated and Th1-mediated response, respectively. Cigarette extracts, especially nicotine, affect the Th1/Th2 balance. We previously reported that nicotine protec...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.00235
更新日期:2020-02-21 00:00:00
abstract::Multiple sclerosis (MS) is the most common neurological immune-mediated disease leading to disability in young adults. The outcome of the disease is unpredictable, and over time, neurological disabilities accumulate. Interferon beta-1b was the first drug to be approved in the 1990s for relapsing-remitting MS to modula...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2019.01564
更新日期:2019-07-11 00:00:00
abstract::Autophagy was initially characterized as a process to digest cellular components, including damaged cell organelles or unused proteins. However, later studies showed that autophagy plays an important role to protect hosts from microbial infections. Accumulating evidences showed the contribution of autophagy itself and...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2016.00047
更新日期:2016-02-18 00:00:00
abstract::Background: Obesity is a condition with a complex pathophysiology characterized by both chronic low-grade inflammation and changes in the gut microbial ecosystem. These alterations can affect the metabolism of tryptophan (TRP), an essential amino acid and precursor of serotonin (5-HT), kynurenine (KYN), and indoles. T...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.00557
更新日期:2020-04-15 00:00:00
abstract::Background: Elevated interleukin-6 (IL-6) and complement activation are associated with detrimental effects of inflammation in coronary artery disease (CAD). The complement anaphylatoxins C5a and C3a interact with their receptors; the highly inflammatory C5aR1, and the C5aR2 and C3aR. We evaluated the effect of the IL...
journal_title:Frontiers in immunology
pub_type: 杂志文章,随机对照试验
doi:10.3389/fimmu.2018.02035
更新日期:2018-09-12 00:00:00
abstract::IgA nephropathy (IgAN) is the dominant type of primary glomerulonephritis worldwide. However, IgAN rarely affects African Blacks and is uncommon in African Americans. Polymeric IgA1 with galactose-deficient hinge-region glycans is recognized as auto-antigen by glycan-specific antibodies, leading to formation of circul...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.00267
更新日期:2020-02-28 00:00:00
abstract::Mycolic acid (MA), a major lipid component of Mycobacterium tuberculosis (Mtb) cell wall, can be presented by the non-polymorphic antigen presenting molecule CD1b to T cells isolated from Mtb-infected individuals. These MA-specific CD1b-restricted T cells are cytotoxic, produce Th1 cytokines, and form memory populatio...
journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.02709
更新日期:2018-11-27 00:00:00
abstract::Metabolic reprogramming is rapidly gaining appreciation in the etiology of immune cell dysfunction in a variety of diseases. Tuberculosis, schistosomiasis, and sarcoidosis represent an important class of diseases characterized by the formation of granulomas, where macrophages are causatively implicated in disease path...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2019.02265
更新日期:2019-10-04 00:00:00
abstract::Sensing of microbe-associated molecular patterns or danger signals by innate immune receptors drives a complex exchange of information. Innate receptor signaling not only triggers transcriptional events but also induces profound changes in metabolic fluxes, redox balance, and metabolite abundance thereby influencing i...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2017.00527
更新日期:2017-05-08 00:00:00