scholarly journals Clinical utility of Basophil and B-cell biomarkers for monitoring disease activity in food allergy and food oral immunotherapy

2020 ◽  
Author(s):  
Theodore Kim ◽  
Richard L. Wasserman ◽  
Oral Alpan ◽  
Atul Shah ◽  
Douglas Jones
Keyword(s):  
United States ◽  
Food Allergy ◽  
B Cells ◽  
Disease Activity ◽  
B Cell ◽  
Clinical Care ◽  
The United States ◽  
High Ratio ◽  
Food Allergies ◽  
Cd73 Expression

As research in the field of food allergy is gaining momentum with new and emerging therapies there is need for both researchers and clinicians to have a better understanding on how to put all this new information into context in clinical care. We are continuously learning from other fields, such as oncology, that a one-shoe-fits all type approaches are becoming the practice of the past and there is need to incorporate markers of disease activity as well as drug selection into clinical care. In the United States, this can happen in two ways; laboratory developed testing and companion diagnostics, generally former leading the path to the later. The findings in this letter is a collaboration between four CLIA/CAP accredited in-office flow cytometry laboratories in Utah, New York and Virginia that are part of very busy food allergy clinics directed by board certified Allergist/Immunologists. The identification of changes in basophils and B cells during oral food immunotherapy are proving to be potentially useful markers in monitoring these patients. We show a high ratio of CD63 to CD203c and CD73 expression on B-cells, compared to healthy non-allergic controls and patients who have outgrown their food allergies. This ratio of basophil surface markers as well as B cell CD73 expression drops as patients are undergoing food-OIT. Quite interestingly, we see a similar low pattern in patients who have non-releaser basophils. Altogether these biomarkers are providing useful and important information monitoring patients and we have validated these assays for clinical use as laboratory developed tests. The Basophil Activation Test is used much more routinely outside the United States, and the powerful correlation it provides to oral food challenge outcomes is making it a very attractive tool. We have just submitted two manuscripts on the validation of the BAT as well as sample stability which is under review elsewhere. We expect more utility of the BAT in the United States in the future. Incorporating biomarkers to clinical care of patients with food allergies will provide to be important in assessing efficacy as well as complications of various therapies as well as monitoring the natural resolution of the food allergies.

Food Allergies

2018 ◽  
Author(s):  
Matthew Greenhawt
Keyword(s):  
United States ◽  
Adverse Reaction ◽  
Food Allergy ◽  
Eosinophilic Esophagitis ◽  
Adverse Reactions ◽  
Action Plan ◽  
The United States ◽  
Oral Allergy Syndrome ◽  
Food Allergies ◽  
Food Protein

Food allergy represents a rapidly growing public health problem in the United States and other westernized nations. Adverse reactions to foods are categorized as either immunologic or nonimmunologic reactions. This distinction is highly important but often confusing to patients and physicians unfamiliar with allergy, who may simply describe any adverse reaction to a food as an “allergy.” A food allergy is an immune-mediated, adverse reaction to one or more protein allergens in a particular food item involving recognition of that protein by specifically targeted IgE or allergen-specific T cells. This chapter discusses the definition, pathophysiology, epidemiology, testing, management, prognosis, and natural history of food allergy. Clinical manifestations are systematically covered, including cutaneous, respiratory, cardiovascular, and gastrointestinal reactions, as well as eosinophilic esophagitis, food protein–induced enterocolitis syndrome, and oral allergy syndrome. Emerging treatments such as food oral immunotherapy are also reviewed. Tables outline signs and symptoms of immediate hypersensitivity reactions to food, the prevalence of major food allergens in the United States, common patterns of cross-reactivity among foods, clinical criteria for the diagnosis of anaphylaxis, and clinical studies involving treatment for food allergies. Figures illustrate the classification of adverse reactions to food, esophageal histology, visual and radiographic features of eosinophilic esophagitis, and a food allergy action plan. This review contains 4 figures, 8 tables, and 64 references. KeyWords: Food allergy, Hypersensitivity, IgE-mediated allergy, Eosinophilic esophagitis, Anaphylaxis

Food Allergies

2018 ◽  
Author(s):  
Matthew Greenhawt
Keyword(s):  
United States ◽  
Adverse Reaction ◽  
Food Allergy ◽  
Eosinophilic Esophagitis ◽  
Adverse Reactions ◽  
Action Plan ◽  
The United States ◽  
Oral Allergy Syndrome ◽  
Food Allergies ◽  
Food Protein

Food allergy represents a rapidly growing public health problem in the United States and other westernized nations. Adverse reactions to foods are categorized as either immunologic or nonimmunologic reactions. This distinction is highly important but often confusing to patients and physicians unfamiliar with allergy, who may simply describe any adverse reaction to a food as an “allergy.” A food allergy is an immune-mediated, adverse reaction to one or more protein allergens in a particular food item involving recognition of that protein by specifically targeted IgE or allergen-specific T cells. This chapter discusses the definition, pathophysiology, epidemiology, testing, management, prognosis, and natural history of food allergy. Clinical manifestations are systematically covered, including cutaneous, respiratory, cardiovascular, and gastrointestinal reactions, as well as eosinophilic esophagitis, food protein–induced enterocolitis syndrome, and oral allergy syndrome. Emerging treatments such as food oral immunotherapy are also reviewed. Tables outline signs and symptoms of immediate hypersensitivity reactions to food, the prevalence of major food allergens in the United States, common patterns of cross-reactivity among foods, clinical criteria for the diagnosis of anaphylaxis, and clinical studies involving treatment for food allergies. Figures illustrate the classification of adverse reactions to food, esophageal histology, visual and radiographic features of eosinophilic esophagitis, and a food allergy action plan. This review contains 4 figures, 8 tables, and 64 references. KeyWords: Food allergy, Hypersensitivity, IgE-mediated allergy, Eosinophilic esophagitis, Anaphylaxis

scholarly journals OP0005 ELEVATED STAT1 EXPRESSION BUT NOT PHOSPHORYLATION IN LUPUS B CELLS CORRELATES WITH DISEASE ACTIVITY AND INCREASED PLASMABLAST SUSCEPTIBILITY

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 4-5
Author(s):  
A. Aue ◽  
F. Szelinski ◽  
S. Weißenberg ◽  
A. Wiedemann ◽  
T. Rose ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
B Cells ◽  
Autoimmune Diseases ◽  
Disease Activity ◽  
B Cell ◽  
Lupus Erythematosus ◽  
Type I ◽  
Type I Ifn ◽  
Systemic Lupus ◽  
B Cell Subsets

Background:Systemic lupus erythematosus (SLE) is characterized by two pathogenic key signatures, type I interferon (IFN) (1.) and B-cell abnormalities (2.). How these signatures are interrelated is not known. Type I-II IFN trigger activation of Janus kinase (JAK) – signal transducer and activator of transcription (STAT).Objectives:JAK-STAT inhibition is an attractive therapeutic possibility for SLE (3.). We assess STAT1 and STAT3 expression and phosphorylation at baseline and after IFN type I and II stimulation in B-cell subpopulations of SLE patients compared to other autoimmune diseases and healthy controls (HD) and related it to disease activity.Methods:Expression of STAT1, pSTAT1, STAT3 and pSTAT3 in B and T-cells of 21 HD, 10 rheumatoid arthritis (RA), 7 primary Sjögren’s (pSS) and 22 SLE patients was analyzed by flow cytometry. STAT1 and STAT3 expression and phosphorylation in PBMCs of SLE patients and HD after IFNα and IFNγ incubation were further investigated.Results:SLE patients showed substantially higher STAT1 but not pSTAT1 in B and T-cell subsets. Increased STAT1 expression in B cell subsets correlated significantly with SLEDAI and Siglec-1 on monocytes, a type I IFN marker (4.). STAT1 activation in plasmablasts was IFNα dependent while monocytes exhibited dependence on IFNγ.Figure 1.Significantly increased expression of STAT1 by SLE B cells(A) Representative histograms of baseline expression of STAT1, pSTAT1, STAT3 and pSTAT3 in CD19+ B cells of SLE patients (orange), HD (black) and isotype controls (grey). (B) Baseline expression of STAT1 and pSTAT1 or (C) STAT3 and pSTAT3 in CD20+CD27-, CD20+CD27+ and CD20lowCD27high B-lineage cells from SLE (orange) patients compared to those from HD (black). Mann Whitney test; ****p≤0.0001.Figure 2.Correlation of STAT1 expression by SLE B cells correlates with type I IFN signature (Siglec-1, CD169) and clinical activity (SLEDAI).Correlation of STAT1 expression in CD20+CD27- näive (p<0.0001, r=0.8766), CD20+CD27+ memory (p<0.0001, r=0.8556) and CD20lowCD27high (p<0.0001, r=0.9396) B cells from SLE patients with (A) Siglec-1 (CD169) expression on CD14+ cells as parameter of type I IFN signature and (B) lupus disease activity (SLEDAI score). Spearman rank coefficient (r) was calculated to identify correlations between these parameters. *p≤0.05, **p≤0.01. (C) STAT1 expression in B cell subsets of a previously undiagnosed, active SLE patient who was subsequently treated with two dosages of prednisolone and reanalyzed.Conclusion:Enhanced expression of STAT1 by B-cells candidates as key node of two immunopathogenic signatures (type I IFN and B-cells) related to important immunopathogenic pathways and lupus activity. We show that STAT1 is activated upon IFNα exposure in SLE plasmablasts. Thus, Jak inhibitors, targeting JAK-STAT pathways, hold promise to block STAT1 expression and control plasmablast induction in SLE.References:[1]Baechler EC, Batliwalla FM, Karypis G, Gaffney PM, Ortmann WA, Espe KJ, et al. Interferon-inducible gene expression signature in peripheral blood cells of patients with severe lupus. Proc Natl Acad Sci U S A. 2003;100(5):2610-5.[2]Lino AC, Dorner T, Bar-Or A, Fillatreau S. Cytokine-producing B cells: a translational view on their roles in human and mouse autoimmune diseases. Immunol Rev. 2016;269(1):130-44.[3]Dorner T, Lipsky PE. Beyond pan-B-cell-directed therapy - new avenues and insights into the pathogenesis of SLE. Nat Rev Rheumatol. 2016;12(11):645-57.[4]Biesen R, Demir C, Barkhudarova F, Grun JR, Steinbrich-Zollner M, Backhaus M, et al. Sialic acid-binding Ig-like lectin 1 expression in inflammatory and resident monocytes is a potential biomarker for monitoring disease activity and success of therapy in systemic lupus erythematosus. Arthritis Rheum. 2008;58(4):1136-45.Disclosure of Interests:Arman Aue: None declared, Franziska Szelinski: None declared, Sarah Weißenberg: None declared, Annika Wiedemann: None declared, Thomas Rose: None declared, Andreia Lino: None declared, Thomas Dörner Grant/research support from: Janssen, Novartis, Roche, UCB, Consultant of: Abbvie, Celgene, Eli Lilly, Roche, Janssen, EMD, Speakers bureau: Eli Lilly, Roche, Samsung, Janssen

scholarly journals Addressing Common Misconceptions in Food Allergy: A Review

Children ◽  
2021 ◽  
Vol 8 (6) ◽  
pp. 497
Author(s):  
Aikaterini Anagnostou
Keyword(s):  
Food Allergy ◽  
The United States ◽  
Specific Ige ◽  
Oral Immunotherapy ◽  
Food Allergies ◽  
Allergy Prevention ◽  
Diagnosis And Management ◽  
Skin Prick Tests ◽  
Food Specific Ige ◽  
Common Misconceptions

Background: Food allergies are common, affecting 1 in 13 school children in the United States and their prevalence is increasing. Many misconceptions exist with regards to food allergy prevention, diagnosis and management. Objective: The main objective of this review is to address misconceptions with regards to food allergies and discuss the optimal, evidence-based approach for patients who carry this diagnosis. Observations: Common misconceptions in terms of food allergy prevention include beliefs that breastfeeding and delayed introduction of allergenic foods prevent the development of food allergies. In terms of diagnosis, statements such as ‘larger skin prick tests or/and higher levels of food-specific IgE can predict the severity of food-induced allergic reactions’, or ‘Tryptase is always elevated in food-induced anaphylaxis’ are inaccurate. Additionally, egg allergy is not a contraindication for receiving the influenza vaccine, food-allergy related fatalities are rare and peanut oral immunotherapy, despite reported benefits, is not a cure for food allergies. Finally, not all infants with eczema will develop food allergies and epinephrine auto-injectors may unfortunately be both unavailable and underused in food-triggered anaphylaxis. Conclusions and relevance: Healthcare professionals must be familiar with recent evidence in the food allergy field and avoid common misunderstandings that may negatively affect prevention, diagnosis and management of this chronic disease.

scholarly journals The expansion of activated naive DNA autoreactive B cells and its association with disease activity in systemic lupus erythematosus patients

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Kittikorn Wangriatisak ◽  
Chokchai Thanadetsuntorn ◽  
Thamonwan Krittayapoositpot ◽  
Chaniya Leepiyasakulchai ◽  
Thanitta Suangtamai ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
B Cells ◽  
Disease Activity ◽  
B Cell ◽  
Lupus Erythematosus ◽  
Systemic Lupus ◽  
Autoreactive B Cells ◽  
Dsdna Antibody ◽  
Cell Subpopulations ◽  
B Cell Subsets

Abstract Background Autoreactive B cells are well recognized as key participants in the pathogenesis of systemic lupus erythematosus (SLE). However, elucidating the particular subset of B cells in producing anti-dsDNA antibodies is limited due to their B cell heterogeneity. This study aimed to identify peripheral B cell subpopulations that display autoreactivity to DNA and contribute to lupus pathogenesis. Methods Flow cytometry was used to detect total B cell subsets (n = 20) and DNA autoreactive B cells (n = 15) in SLE patients’ peripheral blood. Clinical disease activities were assessed in SLE patients using modified SLEDAI-2 K and used for correlation analyses with expanded B cell subsets and DNA autoreactive B cells. Results The increases of circulating double negative 2 (DN2) and activated naïve (aNAV) B cells were significantly observed in SLE patients. Expanded B cell subsets and DNA autoreactive B cells represented a high proportion of aNAV B cells with overexpression of CD69 and CD86. The frequencies of aNAV B cells in total B cell populations were significantly correlated with modified SLEDAI-2 K scores. Further analysis showed that expansion of aNAV DNA autoreactive B cells was more related to disease activity and serum anti-dsDNA antibody levels than to total aNAV B cells. Conclusion Our study demonstrated an expansion of aNAV B cells in SLE patients. The association between the frequency of aNAV B cells and disease activity patients suggested that these expanded B cells may play a role in SLE pathogenesis.

scholarly journals Abortion attempts without clinical supervision among transgender, nonbinary and gender-expansive people in the United States

2021 ◽  
pp. bmjsrh-2020-200966
Author(s):  
Heidi Moseson ◽  
Laura Fix ◽  
Caitlin Gerdts ◽  
Sachiko Ragosta ◽  
Jen Hastings ◽  
...  
Keyword(s):  
United States ◽  
Clinical Supervision ◽  
Online Survey ◽  
Clinical Care ◽  
Insurance Coverage ◽  
Health Insurance Coverage ◽  
The United States ◽  
Physical Trauma ◽  
Abortion Care ◽  
And Gender

BackgroundTransgender, nonbinary and gender-expansive (TGE) people face barriers to abortion care and may consider abortion without clinical supervision.MethodsIn 2019, we recruited participants for an online survey about sexual and reproductive health. Eligible participants were TGE people assigned female or intersex at birth, 18 years and older, from across the United States, and recruited through The PRIDE Study or via online and in-person postings.ResultsOf 1694 TGE participants, 76 people (36% of those ever pregnant) reported considering trying to end a pregnancy on their own without clinical supervision, and a subset of these (n=40; 19% of those ever pregnant) reported attempting to do so. Methods fell into four broad categories: herbs (n=15, 38%), physical trauma (n=10, 25%), vitamin C (n=8, 20%) and substance use (n=7, 18%). Reasons given for abortion without clinical supervision ranged from perceived efficiency and desire for privacy, to structural issues including a lack of health insurance coverage, legal restrictions, denials of or mistreatment within clinical care, and cost.ConclusionsThese data highlight a high proportion of sampled TGE people who have attempted abortion without clinical supervision. This could reflect formidable barriers to facility-based abortion care as well as a strong desire for privacy and autonomy in the abortion process. Efforts are needed to connect TGE people with information on safe and effective methods of self-managed abortion and to dismantle barriers to clinical abortion care so that TGE people may freely choose a safe, effective abortion in either setting.

Synovial Infiltration with CD79a-positive B Cells, But Not Other B Cell Lineage Markers, Correlates with Joint Destruction in Rheumatoid Arthritis

2011 ◽  
Vol 38 (11) ◽  
pp. 2301-2308 ◽  
Author(s):  
YING-QIAN MO ◽  
LIE DAI ◽  
DONG-HUI ZHENG ◽  
LANG-JING ZHU ◽  
XIU-NING WEI ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
B Cells ◽  
Disease Activity ◽  
B Cell ◽  
Cell Density ◽  
Joint Destruction ◽  
Chinese Patients ◽  
Positive Staining ◽  
Synovitis Score ◽  
Sharp Score

Objective.The efficacy of B cell depletion in the treatment of patients with rheumatoid arthritis (RA) has revitalized interest in the pathogenic role(s) of B cells in RA. We evaluated the distribution of synovial B lineage cells and their correlation with histologic disease activity and joint destruction in RA.Methods.Synovial tissue samples were obtained by closed-needle biopsy from 69 Chinese patients with active RA, from 14 patients with osteoarthritis (OA), and from 15 with orthopedic arthropathies (OrthA) as disease controls. Serial tissue sections were stained immunohistochemically for CD79a (pro-B cell to plasma cell), CD20 (B cells), CD38 (plasma cells), CD21 (follicular dendritic cells), CD68 (macrophages), CD3 (T cells), and CD34 (endothelial cells). Densities of positive-staining cells were determined and correlated with histologic disease activity (Krenn 3-component synovitis score) and radiographic joint destruction (Sharp score).Results.Mean sublining CD79a-positive cell density was significantly higher in RA than in OA (p <0.001) or OrthA (p = 0.003). Receiver operating characteristic curve analysis showed that CD79a-positive cell density differentiated RA well from OA [area under the curve (AUC) = 0.79] or OrthA (AUC = 0.75). Spearman’s rank order correlation showed significant correlations between sublining CD79a-positive cell density and the synovitis score (r = 0.714, p < 0.001), total Sharp score (r = 0.490, p < 0.001), and the erosion subscore (r = 0.545, p < 0.001), as well as the joint space narrowing subscore (r = 0.468, p = 0.001) in RA.Conclusion.Synovial CD79a-positive B cells may be a helpful biomarker for histologic disease activity in RA and may be involved in the pathogenesis of joint destruction in RA.

scholarly journals Uptake and Clinical Utility of Multibiomarker Disease Activity Testing in the United States

2018 ◽  
Vol 46 (3) ◽  
pp. 237-244 ◽  
Author(s):  
Jeffrey R. Curtis ◽  
Fenglong Xie ◽  
Shuo Yang ◽  
Maria I. Danila ◽  
Justin K. Owensby ◽  
...  
Keyword(s):  
United States ◽  
Disease Activity ◽  
Clinical Utility ◽  
The United States ◽  
Routine Care ◽  
Subsequent Treatment ◽  
Janus Kinase ◽  
Jak Inhibitor ◽  
Medicare Data ◽  
Multivariable Adjustment

Objective.The clinical utility of the multibiomarker disease activity (MBDA) test for rheumatoid arthritis (RA) management in routine care in the United States has not been thoroughly studied.Methods.Using 2011–2015 Medicare data, we linked each patient with RA to their MBDA test result. Initiation of a biologic or Janus kinase (JAK) inhibitor in the 6 months following MBDA testing was described. Multivariable adjustment evaluated the likelihood of adding or switching biologic/JAK inhibitor, controlling for potential confounders. For patients with high MBDA scores who added a new RA therapy and were subsequently retested, lack of improvement in the MBDA score was evaluated as a predictor of future RA medication failure, defined by the necessity to change RA medications again.Results.Among 60,596 RA patients with MBDA testing, the proportion adding or switching biologics/JAK inhibitor among those not already taking a biologic/JAK inhibitor was 9.0% (low MBDA), 11.8% (moderate MBDA), and 19.7% (high MBDA, p < 0.0001). Similarly, among those already taking biologics/JAK inhibitor, the proportions were 5.2%, 8.3%, and 13.5% (p < 0.0001). After multivariable adjustment, referent to those with low disease MBDA scores, the likelihood of switching was 1.51-fold greater (95% CI 1.35–1.69) for patients with moderate MBDA scores, and 2.62 (2.26–3.05) for patients with high MBDA scores. Among those with high MBDA scores who subsequently added a biologic/JAK inhibitor and were retested, lack of improvement in the MBDA score category was associated with likelihood of future RA treatment failure (OR 1.61, 95% CI 1.27–2.03).Conclusion.The MBDA score was associated with both biologic and JAK inhibitor medication addition/switching and subsequent treatment outcomes.

Sign in / Sign up

Export Citation Format

Share Document