DOCSLIB.ORG

Graft-Versus-Host Disease Cells Suppresses Development Of

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Graft-Versus-Host Disease Cells Suppresses Development Of Adenosine A2A Receptor Agonist −Mediated Increase in Donor-Derived Regulatory T Cells Suppresses Development of Graft-versus-Host Disease This information is current as of September 28, 2021. Kyu Lee Han, Stephenie V. M. Thomas, Sherry M. Koontz, Cattlena M. Changpriroa, Seung-Kwon Ha, Harry L. Malech and Elizabeth M. Kang J Immunol 2013; 190:458-468; Prepublished online 7 December 2012; Downloaded from doi: 10.4049/jimmunol.1201325 http://www.jimmunol.org/content/190/1/458 http://www.jimmunol.org/ References This article cites 52 articles, 20 of which you can access for free at: http://www.jimmunol.org/content/190/1/458.full#ref-list-1 Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists by guest on September 28, 2021 • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Adenosine A2A Receptor Agonist–Mediated Increase in Donor-Derived Regulatory T Cells Suppresses Development of Graft-versus-Host Disease Kyu Lee Han,* Stephenie V. M. Thomas,* Sherry M. Koontz,* Cattlena M. Changpriroa,* Seung-Kwon Ha,† Harry L. Malech,* and Elizabeth M. Kang* Graft-versus-host disease (GVHD) remains a significant complication of allogeneic transplantation. We previously reported that the adenosine A2A receptor (A2AR) specific agonist, ATL146e, decreases the incidence and severity of GVHD in a mouse transplant model. There is increasing interest in treatments that increase CD4+CD25highFoxp3+ regulatory T cells (Tregs) to suppress GVHD. Our current study found in vitro that A2AR selective agonists enhanced TGF-b–induced generation of mouse Tregs 2.3- to 3-fold. We demonstrated in vivo suppression of GVHD with specific A2AR agonists in two different murine GVHD transplant models Downloaded from associated with profound increases in both circulating and target tissue Tregs of donor origin. Three different A2AR agonists of differing potency, ATL146e, ATL370, and ATL1223, all significantly inhibited GVHD-associated weight loss and mortality. At the same time, Tregs shown to be of donor origin increased 5.1- to 7.4-fold in spleen, 2.7- to 4.6-fold in peripheral blood, 2.3- to 4.7-fold in colon, and 3.8- to 4.6-fold in skin. We conclude that specific activation of A2AR inhibits acute GVHD through an increase of donor-derived Tregs. Furthermore, the increased presence of Tregs in target tissues (colon and skin) of A2AR-specific agonist- treated mice is likely the mechanistic basis for the anti-inflammatory effect preventing acute GVHD. The Journal of Immunology, http://www.jimmunol.org/ 2013, 190: 458–468. raft-versus-host disease (GVHD) continues to be a sig- cAMP-elevating agents are known to induce alloreactive T cell nificant cause of morbidity and mortality after allogeneic tolerance and prevent GVHD lethality in murine models (10). G hematopoietic stem cell transplantation (1). Targeted Because the activation of the Gs-coupled adenosine A2A receptor methods to prevent or treat GVHD are in high demand. Regulatory (A2AR) appears to terminate inflammation through the regulation T cells (Tregs) are a subset of CD4+CD25high T cells that express of cells that mediate both innate and adaptive immunity, it is a the FOXP3 and have been shown to suppress the proliferation of promising pharmacological target for the treatment of GVHD by guest on September 28, 2021 T conventional cells and help promote tolerance (2, 3). There is (11). The selective activation of the A2AR has been shown to increasing recognition that Tregs are important in preventing the potently limit inflammation and injury in various inflammatory development, reducing the severity, and/or mediating the resolu- disease models, and the data suggest a central role for this receptor tion of GVHD (4, 5). It has been reported that donor Treg infusions involves a feedback mechanism that inhibits the inflammation as- will suppress the development of GVHD in a mouse model (6–8) sociated with activation of either innate or acquired immunity. A2AR and that the number of Tregs in the peripheral blood and affected agonists have significant protective effects in multiple models of tissues is decreased during the development of acute GVHD in ischemia–reperfusion injury and inhibit the progression of inflam- humans (9). It is likely that Tregs act to modulate immune matory bowel disease and reduce joint destruction because of responses at anatomic sites of GVHD inflammation but also may septic arthrosis (12–16). Furthermore, it has been shown that the act to modulate immunity in central and peripheral lymphoid anti-inflammatory effects of methotrexate are mediated in part via organs as well as in peripheral blood. the induction of adenine nucleotide release from injured tissue and the subsequent activation of A2ARs on local immune cells (17, 18). Notably, T cell tolerance by T cell anergy can also be induced by selective A2AR agonist treatment (19). *Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, We have previously shown that treatment with the specific A2AR National Institutes of Health, Bethesda, MD 20892; and †Life Science Research and Development Center, SK Chemicals, Inc., Sungnam-Si, Gyeonggi-Do 463-410, Re- agonist, ATL146e, decreases the incidence and severity of GVHD public of Korea as well as improves survival of mice in a GVHD transplant model Received for publication May 10, 2012. Accepted for publication October 31, 2012. (20). However, the mechanism of action of ATL146e mediating This work was supported by intramural funds from the National Institute of Allergy this reduction of GVHD mortality was not clearly determined. and Infectious Diseases. There had been a few reports exploring the relationship between K.L.H., S.V.M.T., S.M.K., S.-K.H., and C.M.C. performed experiments; K.L.H., Tregs and A2AR (15, 21–23), but there was no prior evidence to S.-K.H., and S.V.M.T. collected and analyzed data; K.L.H., H.L.M., and E.M.K. show that activation of A R could actually induce immunosup- designed the research; and K.L.H., E.M.K., and H.L.M. wrote the manuscript. 2A pressive Tregs in the setting of GVHD. In our current study, we Address correspondence and reprint requests to Dr. Elizabeth M. Kang, Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National In- found that selective A2AR agonists potently enhanced the TGF-b– stitutes of Health, Building 10, Room 6-3752, 10 Center Drive, MSC-1456, Bethesda, induced generation of mouse Tregs in vitro. In vivo in two GVHD MD 20892-1456. E-mail address: [email protected] mouse transplant models, treatment with selective A2AR agonists + high + Abbreviations used in this article: A2AR, A2A receptor; B6, C57BL/6J; B6-D2, a greatly increased the number of CD4 CD25 Foxp3 Tregs in B6D2F1/J; BM, bone marrow; B6-Thy1.1, B6.PL-Thy1 /CyJ; CsA, cyclosporine A; GVHD, graft-versus-host disease; mTOR, mammalian target of rapamycin; peripheral blood and lymphatic tissue such as the spleen, as well TCD, T cell–depleted; Treg, regulatory T cell. as locally in tissues (skin and colon) that are the target of GVHD www.jimmunol.org/cgi/doi/10.4049/jimmunol.1201325 The Journal of Immunology 459 in these models. Our findings in vitro and in vivo strongly link the permeabilization using a PE-conjugated anti-mouse Foxp3 (FJK-16s) Ab (eBioscience). Control samples were labeled with isotype-matched control action of selective A2AR agonists to the induction of Tregs that act to reduce the development of GVHD in target tissues. Abs. The samples were run on a benchtop flow cytometer (FACSort; BD Biosciences, San Diego, CA) with a minimum of 10,000 events collected. Analysis was performed with Cell Quest (Tree Star, Ashland, OR). Materials and Methods Measurement of serum cytokines Mice Cytokine concentrations in serum samples were measured using mouse For these studies, five mouse strains (with relevant H2 major histocom- cytokine/chemokine multiplex immunoassay kits (Linco, St. Charles, MO) patibility type indicated) were purchased from The Jackson Laboratory (Bar with the BioPlex system (Bio-Rad, Hercules, CA) using Luminex tech- Harbor, ME): C57BL/6J (H2-Kb); B6.PL-Thy1a/CyJ (congenic to C57BL/ b d nology. Serum levels of TGF-b were measured by ELISA (R&D Systems, 6J carrying the Thy 1.1 allele [H2-K ]); BALB/c (H2-K ); B6D2F1/J (F1 Minneapolis, MN). hybrid cross between C57BL/6J female 3 DBA/2J male [H2-Kb/d]); and B6. Cg-Foxp3sf/J (Foxp3 deficient scurfy on C57BL/6J background [H2-Kb]). Histopathological analysis and immunohistochemistry The National Institute of Allergy and Infectious Disease Animal Care and Use Committee (Bethesda, MD) approved all animal studies (Institutional Skin and colon were harvested from euthanized mice and fixed in 4% Animal Care and Use Committee–approved protocol LHD-3E). paraformaldehyde in PBS (pH 7.4) and embedded in paraffin. Sections (4 mm) were subjected to standard H&E staining and immunochemical Specific A2AR agonists staining. Each section was then scored separately by a board-certified toxicologic pathologist, blinded to animal status, according to the pub- The highly specific A2AR agonists ATL146e, ATL370, and ATL1223 were lished criteria (25–27).
Load more

Recommended publications
  • Allergy and Immunology Milestones
    Allergy and Immunology Milestones The Accreditation Council for Graduate Medical Education Second Revision: August 2019 First Revision: August 2013 Allergy and Immunology Milestones The Milestones are designed only for use in evaluation of residents in the context of their participation in ACGME-accredited residency or fellowship programs. The Milestones provide a framework for the assessment of the development of the resident in key dimensions of the elements of physician competency in a specialty or subspecialty. They neither represent the entirety of the dimensions of the six domains of physician competency, nor are they designed to be relevant in any other context. i Allergy and Immunology Milestones Work Group Amal Assa’ad, MD Evelyn Lomasney, MD Taylor Atchley, MD Aidan Long, MD T. Prescott Atkinson, MD, PhD Mike Nelson, MD Laura Edgar, EdD, CAE Princess Ogbogu, MD Beverly Huckman, BA* Kelly Stone, MD, PhD Bruce Lanser, MD The ACGME would like to thank the following organizations for their continued support in the development of the Milestones: American Board of Allergy and Immunology American Academy of Allergy, Asthma, and Immunology Review Committee for Allergy and Immunology *Acknowledgments: The Work Group and the ACGME would like to honor Beverly Huckman, for her contributions as the non-physician member of the milestones work group. She will be greatly missed. ii Understanding Milestone Levels and Reporting This document presents the Milestones, which programs use in a semi-annual review of resident performance, and then report to the ACGME. Milestones are knowledge, skills, attitudes, and other attributes for each of the ACGME Competencies organized in a developmental framework.
    [Show full text]
  • Hypersensitivity Reactions (Types I, II, III, IV)
    Hypersensitivity Reactions (Types I, II, III, IV) April 15, 2009 Inflammatory response - local, eliminates antigen without extensively damaging the host’s tissue. Hypersensitivity - immune & inflammatory responses that are harmful to the host (von Pirquet, 1906) - Type I Produce effector molecules Capable of ingesting foreign Particles Association with parasite infection Modified from Abbas, Lichtman & Pillai, Table 19-1 Type I hypersensitivity response IgE VH V L Cε1 CL Binds to mast cell Normal serum level = 0.0003 mg/ml Binds Fc region of IgE Link Intracellular signal trans. Initiation of degranulation Larche et al. Nat. Rev. Immunol 6:761-771, 2006 Abbas, Lichtman & Pillai,19-8 Factors in the development of allergic diseases • Geographical distribution • Environmental factors - climate, air pollution, socioeconomic status • Genetic risk factors • “Hygiene hypothesis” – Older siblings, day care – Exposure to certain foods, farm animals – Exposure to antibiotics during infancy • Cytokine milieu Adapted from Bach, JF. N Engl J Med 347:911, 2002. Upham & Holt. Curr Opin Allergy Clin Immunol 5:167, 2005 Also: Papadopoulos and Kalobatsou. Curr Op Allergy Clin Immunol 7:91-95, 2007 IgE-mediated diseases in humans • Systemic (anaphylactic shock) •Asthma – Classification by immunopathological phenotype can be used to determine management strategies • Hay fever (allergic rhinitis) • Allergic conjunctivitis • Skin reactions • Food allergies Diseases in Humans (I) • Systemic anaphylaxis - potentially fatal - due to food ingestion (eggs, shellfish,
    [Show full text]
  • What You Need to Know About the New Guidelines for the Diagnosis and Management of Food Allergy in the U.S
    Allergy guidelines insert_Layout 1 9/26/11 1:36 PM Page 1 What you need to know about the new guidelines for the diagnosis and management of food allergy in the U.S. V OLUME 126, N O . 6 D ECEMBER 2010 • Tests for food-specific IgE are recom- Overview www.jacionline.org • The Guidelines, sponsored by the NIH Supplement to mended to assist in diagnosis, but should (NIAID), are based upon expert opinion THE JOURNAL OF not be relied upon as a sole means to di- Allergy ANDClinical and a comprehensive literature review. Immunology agnose food allergy. The medical history/ AAP had input on the document.1,2 exam are recommended to aid in diag- nosis. A medically monitored feeding Guidelines for the Diagnosis and Management Definitions of Food Allergy in the United States: Report of the (food challenge) is considered the most NIAID-Sponsored Expert Panel • Food allergy was defined as an adverse definitive test for food allergy. health effect arising from a specific im- • Food-specific IgE testing has numerous mune response. limitations; positive tests are not intrin- • Food allergies result in IgE-mediated sically diagnostic and reactions some- immediate reactions (e.g., anaphylaxis) OFFICIAL JOURNAL OF times occur with negative tests. These and several chronic diseases (e.g., ente- Supported by the Food Allergy Initiative issues are also reviewed in an AAP Clini - rocolitis syndromes, eosinophilic esopha - cal Report.3 Testing “food panels” with- gitis, etc), in which IgE may not play an important role. out considering history is often mis - leading. Tests selected to evaluate food allergy should be Epidemiology and Natural History based on the patient’s medical history and not comprise • Food allergy is more common in children than adults, large general panels of food allergens.
    [Show full text]
  • What Is the Difference Between Allergy, Sensitivity & Intolerance?
    What Is the Difference Between Allergy, Sensitivity & Intolerance? The primary difference between an allergy, a sensitivity, and an intolerance is that an allergy is characterized by an immune system reaction to a substance, a sensitivity involves no immune response and an intolerance is characterized by the body lacking a chemical or enzyme needed to digest certain food. All, however, can be quite serious, and a range of symptoms can be caused by allergies, sensitivities, and intolerances. For this reason, it is a good idea to see a doctor about symptoms which appear to be linked to exposure to certain substances, to figure out precisely what is going on. Allergy: Although the word "Allergy" is commonly used to describe any unpleasant reaction to a drug, food, insect sting or chemical, this can be misleading. The word should only really be used to describe a reaction produced when the body meets a normally harmless substance, which has been “remembered" from a previous exposure and subsequently produces the "IgE" antibody. In the case of an allergy, the immune system learns to attack a particular substance for an unknown reason. In order for an allergy to develop, someone must be exposed to the substance at least once before the allergy will manifest. A classic example of an allergy is a peanut allergy, in which the immune system regards peanuts as harmful, and goes into overdrive when someone consumes peanuts or is exposed to peanut products. Some common symptoms linked with allergies are dermatological symptoms like eczema and hives, respiratory problems, anaphylaxis, rhinitis, and shock.
    [Show full text]
  • Allergy/Immunology
    259754_text 2-14 2/14/11 2:35 PM Page 17 To facilitate physician referrals, call: (901) 287-7337 or (866) 870-5570 Allergy/Immunology Le Bonheur Children’s Hospital treats more children with allergy and immunology problems than any other diagnosis. At Le Bonheur, board-certified pediatric allergists/immunologists perform comprehensive labora- tory testing to diagnose the child’s condition. Services include treatment and testing for: • Asthma • Allergic rhinitis • Immune disorders • Severe reactions to food, insect stings or drugs • Skin allergies Major diagnostic procedures include: • Secretion cytology • Allergy skin tests • Pulmonary function studies • Penicillin skin testing • RAST testing • Circulating eosinophil count • Bronchial challenge • EIA tests • Serum immunoglobulin levels Camp Wezbegon Camp Wezbegon is a fun-filled, one-week camp designed specifically for children ages 9 - 13 who have asthma. The camp’s emphasis is on having fun while learning. Campers participate in a variety of outdoor activities including swimming, hiking and nature study. They also attend a daily class on asthma manage- ment. Volunteer physicians, nurses, respiratory therapists, pharmacists, nutritionists and child life volunteers provide 24-hour medical supervision. A committee selects the campers, and services are provided free of charge. The camp is made possible through generous funding from donors. .................................Mary Ellen Conley, MD .................................Betty Lew, MD UT Le Bonheur Pediatric Specialists UT Le Bonheur
    [Show full text]
  • Food Allergens in the Bakery
    Food Allergens in the Bakery Major food allergens are: fish, peanuts, wheat, soy, tree nuts (such as almonds, filberts/hazelnuts, pecans, pistachios, walnuts), eggs, milk/dairy, and shellfish (such as shrimp, crab, or lobster). A food allergen can cause illness or death in some of your customers. Other sensitive ingredients include lactose, gluten, and sesame. Be aware of bakery products that contain allergens. The list below is not a full listing of potential allergens, but a list of more common ones found in bakery products: CMYK Milk/ • Butter • Sour Cream Lactose • Cream • Whipped Cream • Ice Cream • Yogurt • Milk • Cheese • Whey • Buttermilk • Caramel color or flavor Eggs • Egg washes—used on breads, sweet goods, • Egg substitutes made pastries, and pies with egg whites • Edible cake decorations Wheat/ • Wheat: • Barley Gluten • triticale • flour • Oats • graham • hydrolyzed wheat • Rye • kamut protein • Wheat derivatives: • semolina • matzoh • bran • grass • spelt • sprouted wheat • durum • malt • faro • wheat germ oil • germ • sprouts • einkorn • whole wheat berries • gluten • starch Peanuts/ • Artificial nuts • Almonds Tree Nuts • May be made from peanuts with tree nut • Filberts/Hazelnuts flavoring added • Peanuts • Marzipan • Pecans • Made from almond paste; used in cookies, • Pistachios sweet goods, and cakes • Walnuts • Pesto • May contain pine nuts or walnuts; added to some focaccia and savory breads Soy • Lecithin • Soy flour • Guar gum • Soy milk How Can I Help My Customers? • Some customers will ask you for ingredient information to make informed decisions. • Know where to find labels or product ingredient information to give them. • DO NOT use this information to make health recommendations. Let customers decide. For more in-depth information on the top 8 food allergens, see FARE’s Tips for Avoiding Your Allergen at foodallergy.org.
    [Show full text]
  • Food Allergy Glossary.Pdf
    G看ossary of Food A=e「gy Te「ms The fo=owing words and phrases a「e often used to ta肱about food訓ergies. 囲 Acute symptoms - Physical signs that begin suddenly or last only a short amo踊t Of time. Adrenaline - A hormone made by the body (also known as epinephrine), Adver§e leaCtions - An unwanted response to a food 〈such as a rash, VOmiting, etC.). A=ergen - Anything that causes an a=ergic reaction. Allergic reaction - An immune system response to something that the body mistakes as a th「eat. Ånaphyiaxis - A serious a=ergic reaction that comes on quickIy and may cause death. Anaphylactic shock - A symptom of anaphylaxis where there is a severe drop in b10Od pressure, Angiodema (or edemaトSwe用ng of a part of the body. Antibody - A protein in the biood that is meant to identify and a廿ack fo「eign objects like bacte「ia o「 v血ses. In food a=ergies, these antibodies mistake some food p「Oteins as a foreign object. Antigen - Anything that causes the immune system to react when it ente「s the body. Antihis置amine葛A medicine used to bIock the effects of histamine, a Chemical that is reIeased during an aiIergic reaction. Antihistamines do not stop anaphylaxis. Asthma - A chronic disease of the lungs in which the airways become blocked o川arrowed. This biockage can make it hard to breathe. Many people with food a=ergies aIso have asthma. Those wjth both asthma and food a=ergies are at a higher risk for a severe aiiergic reaction. 匿 Biphasic reaction - An aIIergic reaction that h∂S tWO StageS.
    [Show full text]
  • Inflammatory Myopathies with Cutaneous Involvement
    DOI: 10.1515/folmed-2017-0003 REVIEW Infl ammatory Myopathies with Cutaneous Involvement: from Diagnosis to Therapy Lyubomir A. Dourmishev Department of Dermatology and Venereology, Medical University of Sofi a, Sofi a, Bulgaria Correspondence: The group of idiopathic infl ammatory myopathies (IIM) include various disorders Lyubomir A. Dourmishev, Depart- of skeletal muscles with or without skin involvement. The most common types are ment of Dermatology and Venere- dermatomyositis (DM), polymyositis (PM), inclusion body myositis (IBM) and nec- ology, Medical University of Sofi a, rotizing autoimmune myopathy (NAM). Dermatomyositis subdivides into various 1 St Georgi Sofi iski St., clinical forms such as juvenile, amyopathic or paraneoplastic dermatomyositis, 1431 Sofi a, Bulgaria E-mail: [email protected] scleromyositis, overlap or anti-synthetase syndromes, etc. Tel: +3592 9230438 Recently, numerous new antibodies defi ning the characteristic clinical phenotype Received: 08 March 2016 have been described as anti-MDA5 antibodies associated with interstitial lung Accepted: 19 July 2016 disease and amyopathic dermatomyositis or anti-TIF1γ antibodies as markers for Published Online: 22 Nov 2016 paraneoplastic dermatomyositis. Moreover, new clinical entities as drug-induced Published: 27 March 2017 dermatomyositis are presumed, since some medications may induce, or trigger infl ammatory myopathies. Key words: idiopathic infl am- matory myopathies, cutaneous Knowledge of the complex methods and techniques required to diagnose the involvement, clinical variants, disease is of great importance in clinical practice. The variety of clinical variants diagnosis, therapy needs diagnosis because of the diff ering prognosis and therapeutic modalities. Citation: Dourmishev LA. Infl am- matory myopathies with cutane- ous involvement: from diagnosis to therapy. Folia Medica 2017;59(1):7-13.
    [Show full text]
  • Monoclonal Antibodies in Treating Food Allergy: a New Therapeutic Horizon
    nutrients Review Monoclonal Antibodies in Treating Food Allergy: A New Therapeutic Horizon Sara Manti 1 , Giulia Pecora 1,†, Francesca Patanè 1,†, Alessandro Giallongo 1,* , Giuseppe Fabio Parisi 1 , Maria Papale 1, Amelia Licari 2 , Gian Luigi Marseglia 2 and Salvatore Leonardi 1 1 Pediatric Respiratory Unit, Department of Clinical and Experimental Medicine, San Marco Hospital, University of Catania, Via Santa Sofia 78, 95123 Catania, Italy; [email protected] (S.M.); [email protected] (G.P.); [email protected] (F.P.); [email protected] (G.F.P.); [email protected] (M.P.); [email protected] (S.L.) 2 Pediatric Clinic, Department of Pediatrics, Fondazione IRCCS Policlinico San Matteo, University of Pavia, 27100 Pavia, Italy; [email protected] (A.L.); [email protected] (G.L.M.) * Correspondence: [email protected]; Tel.: +39-095-4794-181 † These authors contributed equally to this work. Abstract: Food allergy (FA) is a pathological immune response, potentially deadly, induced by exposure to an innocuous and specific food allergen. To date, there is no specific treatment for FAs; thus, dietary avoidance and symptomatic medications represent the standard treatment for managing them. Recently, several therapeutic strategies for FAs, such as sublingual and epicutaneous immunotherapy and monoclonal antibodies, have shown long-term safety and benefits in clinical practice. This review summarizes the current evidence on changes in treating FA, focusing on monoclonal antibodies, which have recently provided encouraging data as therapeutic weapons modifying the disease course. Citation: Manti, S.; Pecora, G.; Patanè, F.; Giallongo, A.; Parisi, G.F.; Keywords: monoclonal antibodies; food allergy; biologics; children; adults Papale, M.; Licari, A.; Marseglia, G.L.; Leonardi, S.
    [Show full text]
  • Mast Cell Involvement in Fibrosis in Chronic Graft-Versus-Host Disease
    International Journal of Molecular Sciences Review Mast Cell Involvement in Fibrosis in Chronic Graft-Versus-Host Disease Ethan Strattan and Gerhard Carl Hildebrandt * Division of Hematology and Blood & Marrow Transplant, Markey Cancer Center, University of Kentucky, Lexington, KY 40536, USA; [email protected] * Correspondence: [email protected] Abstract: Allogeneic hematopoietic stem cell transplantation (HSCT) is most commonly a treatment for inborn defects of hematopoiesis or acute leukemias. Widespread use of HSCT, a potentially curative therapy, is hampered by onset of graft-versus-host disease (GVHD), classified as either acute or chronic GVHD. While the pathology of acute GVHD is better understood, factors driving GVHD at the cellular and molecular level are less clear. Mast cells are an arm of the immune system that are known for atopic disease. However, studies have demonstrated that they can play important roles in tissue homeostasis and wound healing, and mast cell dysregulation can lead to fibrotic disease. Interestingly, in chronic GVHD, aberrant wound healing mechanisms lead to pathological fibrosis, but the cellular etiology driving this is not well-understood, although some studies have implicated mast cells. Given this novel role, we here review the literature for studies of mast cell involvement in the context of chronic GVHD. While there are few publications on this topic, the papers excellently characterized a niche for mast cells in chronic GVHD. These findings may be extended to other fibrosing diseases in order to better target mast cells or their mediators for treatment of fibrotic disease. Citation: Strattan, E.; Hildebrandt, Keywords: mast cells; GVHD; fibrosis; transplant; autoimmune; pathogenesis G.C.
    [Show full text]
  • Clinical Aspects of Overlap Syndrome - Case Report and Literature Review
    Arch Clin Biomed Res 2018; 2 (4): 117-131 DOI: 10.26502/acbr.5017051 Case Report Clinical Aspects of Overlap Syndrome - Case Report and Literature Review Bogna Grygiel-Górniak*, Oscar Nicholas Godtfredsen, Gunnar Nyborg Eid, Nicholas Werczak, Mariusz Puszczewicz Department of Rheumatology and Internal Medicine, Poznan University of Medical Sciences, Poznan, Poland *Corresponding Author: Bogna Grygiel-Górniak, Department of Rheumatology and Internal Medicine, Poznan University of Medical Sciences, Poznan, Poland, E-mail: [email protected] Received: 04 May 2018; Accepted: 08 May 2018; Published: 10 May 2018 Abstract We report a patient with overlap syndrome (systemic sclerosis (SSc) and polymyositis (PM)). The heterogeneous nature of systemic sclerosis may lead to a great diversity in the clinical presentation of the disease. With this case report we aim to demonstrate clinical manifestations of systemic sclerosis and polymyositis in an overlap-syndrome, with support from antibody profile and laboratory data. Keywords: Overlap syndrome; Systemic sclerosis; Polymyositis; Pulmonary fibrosis; Treatment 1. Case Report A 51-year old female patient came to the Pulmonology Ward in 2015 complaining of shortness of breath and reduced exercise tolerance for approximately 1 year. Clinical examination revealed a rash on the neck that spread throughout the upper part of thorax, in addition to swollen, reddish fingers with skin stiffness on the hands. The patient also suffered from a swollen face and swollen eyelids. On auscultation, crackles were heard in the lower lung fields. On X-ray, changes in the interstitium were seen, and computer tomography confirmed fibrotic areas located peripherally in the lower lobes. In HRCT (high definition computer tomography) fibrosis was found in both lungs peripherally in the lower posterior lobes.
    [Show full text]
  • Viagra Online Order
    What is an ALLERGY? What are the Symptoms of Ear, Nose and Throat Allergies? llergy is a condition, often inherited, People often think of allergy as only “hay fever,” in which the immune system of the with sneezing, runny nose, nasal stuffiness and A affected person reacts to something itchy, watery eyes. However, allergies can also that is either eaten, touched, or inhaled that cause symptoms such as chronic “sinus” doesn’t affect most other people. The patient’s problems, excess nasal and throat drainage (post immune system reacts to this substance as if it nasal drip), head congestion, frequent “colds,” were an “enemy invader” (like a virus). This hoarse voice, eczema (skin allergies), recurring ear infections, hearing loss, dizziness, chronic reaction leads to symptoms that often adversely cough and asthma. Even stomach and intestinal affect the patient’s work, play, rest, and overall problems as well as excessive fatigue can be What causes Symptoms to Begin? quality of life. symptoms of allergy. Symptoms of ear, nose, There is no “usual” way for an allergy to begin; and throat allergies may include: the onset may be sudden or gradual. Often, Allergens Cause Allergies i Repeated sneezing symptoms develop following an unusual stress to the immune symptom, such as a severe Any substance that triggers an allergic reaction i Nasal itching and rubbing viral infection. is called an allergen. Allergens “invade” the i Nasal congestion body by being inhaled, swallowed or injected, i Runny nose Can an Allergy be Outgrown? or they may be absorbed through the skin. i Dark circles under the eyes No, but it is common for people to change the Common allergens include pollen, dust i Crease across bridge of nose way their allergic symptoms affect them.
    [Show full text]