Manish Butte

Highly sensitive optoelectrical biosensor for multiplex allergy diagnosis.

Biosens Bioelectron. 2020 Jul 15;166:112438

Authors: Mas S, Badran AA, Juárez MJ, Fernández de Rojas DH, Morais S, Maquieira Á

Abstract
Compact multiplexed biosensors systems hold great potential for diagnosis of diseases where the detection of multiple biomarkers is required. Hypersensitivity Immunoglobulin E mediated syndromes are primary immunodeficiency disorders associated with sensitization to allergens. Assessing immunoglobulin E (IgE) sensitization to allergens is an important strategy for allergy diagnosis. Here, we report for the first time a reliable, flexible and cost-effective optoelectrical biosensor system for the simultaneous determination of total and allergen-specific IgE and IgG, antibodies using an immunogold-silver signal amplification method. The biosensor was constructed on a regular digital versatile disc (DVD) to immobilize a panel of 12 allergen extracts or pure proteins in microarray format, as a proof of concept. The multiplexed biosensor showed a limit of detection of 0.26 IU/mL (624 pg/mL) and 14 ng/mL for IgE and IgG antibodies, respectively. The system was successfully applied in a cohort of 127 human serum samples, showing good sensitivity (97.6%) as well as specificity (85.7%), and an excellent area under the curve (AUC) value was found at 0.977 (confidence interval, CI 0.957 to 0.990) as compared and validated with a reference clinical immunofluorescence assay, confirming an excellent correlation between both techniques. The multiplex biosensor system with on-demand panel composition can be used fully autonomously in clinical or mobile laboratory settings without the need for any additional medical equipment, with which could make it suitable for massive allergy screening campaigns to better define sensitization profiles.

PMID: 32755808 [PubMed – as supplied by publisher]

Powered by WPeMatico

Newborn Screening through TREC, TREC/KREC system for Primary Immunodeficiency with limitation of TREC/KREC. Comprehensive review.

Antiinflamm Antiallergy Agents Med Chem. 2020 Jul 30;:

Authors: Shinwari K, Bolkov M, Tuzankina IA, Chereshnev VA

Abstract
INTRODUCTION: Newborn screening (NBS) by quantifying T cell receptor excision circles (TRECs) and Kappa receptor excision circles in neonatal dried blood spots (DBS) enables early diagnosis of different types of primary immune deficiencies. Global newborn screening for PID, using an assay to detect T-cell receptor excision circles (TREC) in dried blood spots (DBS), is now being performed in all states in the United States. In this review, we discuss the development and outcomes of TREC, TREC/KREC combines screening, and continued challenges to implementation.
OBJECTIVE: To review the diagnostic performance of published articles for TREC and TREC/ KREC based NBS for PID and its different types.
METHODS: Different research resources were used to get an approach for the published data of TREС and KREC based NBS for PID like PubMed, Scopus, Google Scholar, Research gate EMBASE. We extracted TREC and KREC screening Publisher with years of publication, content and cut-off values, and a number of retests, repeat DBS, and referrals from the different published pilot, pilot cohort, Case series, and cohort studies.
RESULTS: We included the results of TREC, combine TREC/KREC system based NBS screening from different research articles,and divided these results between the Pilot studies, case series, and cohort. For each of these studies, different parameter data are excluded from different articles. Thirteen studies were included, re-confirming 89 known SCID cases in case series and reporting 53 new SCID cases in 3.15 million newborns. Individual TREC contents in all SCID patients were <25 TRECs/μl (except in those evaluated with the New York State assay).
CONCLUSION: TREC and KREC sensitivity for typical SCID and other types of PID was100 %. It shows its importance and anticipating the significance of implementation in different undeveloped and developed countries in the NBS program in upcoming years. Data adapting the screening algorithm for pre-term/ill infants reduce the amount of false-positive test results.

PMID: 32748762 [PubMed – as supplied by publisher]

Powered by WPeMatico

Rituximab and antimetabolite treatment of granulomatous and lymphocytic interstitial lung disease in common variable immunodeficiency.

J Allergy Clin Immunol. 2020 Jul 31;:

Authors: Verbsky JW, Hintermeyer MK, Simpson PM, Feng M, Barbeau J, Rao N, Cool CD, Sosa-Lozano LA, Baruah D, Hammelev E, Busalacchi A, Rymaszewski A, Woodliff J, Chen S, Bausch-Jurken M, Routes JM

Abstract
BACKGROUND: Granulomatous and lymphocytic interstitial lung disease (GLILD) is a life-threatening complication in patients with CVID, but the optimal treatment is unknown.
OBJECTIVE: Determine if rituximab with azathioprine or mycophenolate mofetil improves the HRCT of the chest and/or PFTs in patients with CVID and GLILD.
METHODS: A retrospective chart review was performed of clinical and laboratory data in 39 patients with CVID and GLILD who completed immunosuppressive therapy. Chest HRCT scans, performed prior to therapy and after the conclusion of therapy, were blinded, randomized, and scored independently by two radiologists. Differences between pre- and post-treatment HRCT scores, PFTs and lymphocyte subsets were analyzed. Whole exome sequencing was performed on all patients.
RESULTS: Immunosuppressive therapy improved CT scores (p<0.0001), FVC (p=0.0017), FEV1 (p=0.037), TLC (p=0.013) but not DLCO (p=0.12). Nine patients relapsed and six completed re-treatment, and 5/6 (83%) of these patients had improved HRCT scores (p=0.063). Relapse was associated with an increased number of B cells (p=0.016) and activated CD4 T cells (p=0.016). Four (10%) patients had pneumonia on active treatment, and 2 (5%) patients died after completion of therapy. Eight (21%) patients had a damaging mutation in a gene known to predispose (TNFRSF13B, n=3) or cause a CVID-like PID (CTLA4, n=2; KMT2D, n=2; BIRC4, n=1). Immunosuppression improved the HRCT scores in patients with (p=0.0078) and without (p<0.0001) a damaging mutation.
CONCLUSIONS: Immunosuppressive therapy improved the radiographic abnormalities and pulmonary function of patients with GLILD. A majority of patients had sustained remissions.

PMID: 32745555 [PubMed – as supplied by publisher]

Powered by WPeMatico

The clinical implications of selective IgA deficiency.

J Transl Autoimmun. 2019 Dec;2:100025

Authors: Swain S, Selmi C, Gershwin ME, Teuber SS

Abstract
Selective IgA deficiency (SIgAD) is the most common primary immunodeficiency but does not always result in clinical disease. This may in part be due to the definition based on serum IgA, while most IgA is secreted at mucosal surfaces, not amenable to measurement. Clinical complications include increased risk of sinopulmonary infections with bacteria and viruses, gastrointestinal infections with a predilection for Giardia lamblia, a myriad of autoimmune diseases including systemic lupus erythematosus, hyper- and hypo-thyroidism, Type 1 diabetes, celiac disease, and rarely, malignancy. SIgAD must be differentiated from IgA deficiency that may be seen with IgG2 or IgG4 deficiency, specific antibody deficiency, or as an early manifestation prior to a diagnosis of common variable immunodeficiency. Secondary IgA deficiency is increasingly recognized and may be due to medications such as anti-epileptics, or antibiotics with disruption of the microbiome which can influence IgA levels, infections or malignancies. Patients with SIgAD should be monitored at regular intervals and educated to be aware of particular complications. There is a rare chance of development of anti-IgA IgE antibodies in patients with complete deficiency, which can result in anaphylaxis if blood products with IgA are administered. Prophylactic antibiotics may be indicated in some cases, and very rarely, supplemental IgG infusions.

PMID: 32743511 [PubMed]

Powered by WPeMatico