DOCSLIB.ORG

Haematological Abnormalities in Human Immunodeficiency Virus (HIV) Disease

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Haematological Abnormalities in Human Immunodeficiency Virus (HIV) Disease J Clin Pathol: first published as 10.1136/jcp.41.7.711 on 1 July 1988. Downloaded from J Clin Pathol 1988;41:711-715 Review article Haematological abnormalities in human immunodeficiency virus (HIV) disease CHRISTINE COSTELLO From the Department ofHaematology, St Stephen's Hospital, London Peripheral blood and bone marrow changes are com- patients with AIDS and opportunistic tumours.2 Care monly seen in disease associated with human immun- must be taken when interpreting the ratio of T helper odeficiency virus (HIV). This annotation aims to to T suppressor cells. Only when there is lymphopenia summarise these changes and to suggest possible does a decreased ratio indicate depletion of T helper factors entailed in their occurrence. cells. In patients with a normal lymphocyte count a decreased ratio might result either from T helper cell The wideranging clinical and pathological changes in depletion or from T suppressor cell increase. patients infected with HIV virus are both fascinating Mir found a 79% incidence of lymphopenia in 40 and challenging to physicians and pathologists alike. patients with AIDS and in our series of 925 HIV Haematological abnormalities are well recognised in antibody positive patients studied during 1987, 305 HIV disease and result from diverse influences on the (33%) were lymphopenic; most of these patients had haemopoietic tissue. Changes in the peripheral blood AIDS or ARC.3 and bone marrow may reflect disease elsewhere in the Granulocytopenia is a less well recognised feature of body, may result from treatment for that disease, may HIV disease but was seen in 185 (20%) of 925 HIV reflect an attempt to attack the HIV virus itself, or may antibody positive patients (Haematological features of seem to be isolated haematological disorders. Only by HIV disease, Costello C, unpublished observations). http://jcp.bmj.com/ monitoring blood changes and correlating them with In Treacy's series two thirds ofthe patients with AIDS the clinical state of the patient can we hope to or ARC having bone marrow examinations were understand the mechanisms involved and to suggest granulocytopenic' and this figure was similar in a what their clinical importance might be. larger series of 60 patients at St Stephen's Hospital undergoing bone marrow examinations (Proceedings Peripheral blood changes of meeting on prospective indications for intravenous immunoglobulin, 1988).3 on October 1, 2021 by guest. Protected copyright. Leucopenia is common in patients with HIV infection A left shift in the granulocytic series is a common and seems to correlate with the severity of the disease. finding'4 and may reflect the clinical condition of the Two hundred and twelve (23%) ofa series of 925 HIV patient. The pathogenesis of neutropenia is obscure, antibody positive patients at this hospital were though several factors are likely to be important: leucopenic at some stage during their illness, and 88% concurrent infections, drugs which suppress the ofpatients with acquired immune deficiency syndrome marrow, and probably, in some cases, an immune (AIDS) or AIDS-related complex (ARC) were process. Murphy et al studied 105 HIV antibody leucopenic at presentation.' Ofinterest is the contribu- positive patients and found neutropenia in 20% of tion of lymphopenia, neutropenia, and granulo- patients with AIDS, 25% of patients with persistent cytopenia to the reduction of total number of white generalised lymphadenopathy (PGL), but none of 26 cells. asymptomatic HIV antibody positive subjects.5 He Lymphopenia in HIV disease is common, cells of performed granulocyte immunofluorescence tests the T helper phenotype being specifically depleted. In (GIFT) on 34 HIV antibody positive men, two with patients with AIDS and opportunistic infections AIDS, 24 with PGL, and eight who were asymp- immune function is more severely disturbed than in tomatic. Seven of the 34 were neutropenic and in four the GIFT reaction was positive. Six patients with Accepted for publication 3 March 1988 normal neutrophil counts also showed positive GIFT 711 J Clin Pathol: first published as 10.1136/jcp.41.7.711 on 1 July 1988. Downloaded from 712 Costello tests but in none of these patients with positive immune in aetiology, related to drugs, or part of the reactions was there any correlation with concentra- pancytopenia often seen in ill patients with opportun- tions of circulating immune complexes. Thus in at istic infections. least some patients with neutropenia an autoimmune The incidence ofthrombocytopenia has perhaps not mechanism might be implicated. been fully appreciated. The initial reluctance to put Van der Lehe also found granulocyte bound samples through a whole blood counter led to an immunoglobulin in patients with HIV disease and to a evaluation ofplatelet numbers often being made on a lesser extent in high risk patients without evidence of blood film. Mild degrees of thrombocytopenia were HIV disease.6 In some cases acid eluates from the quite likely overlooked. At this hospital we found a granulocytes contained immunoglobulins reacting 13% incidence of thrombocytopenia (121 of 925 with normal granulocytes, thus indicating that they patients studied over 12 months) in patients who were were autoantibodies rather than non-specifically at risk for HIV disease. Although most ofthe patients bound immune complexes. Presumably the immune had either AIDS or ARC, 12% of the patients with imbalance in HIV infected patients may result in the thrombocytopenia were HIV antibody positive, and production of autoantibodies to blood cells. asymptomatic. An alternative cause for the neutropenia seen in The diagnosis of immune thrombocytopenia is patients with HIV disease might be decreased bone often made on clinical and bone marrow findings as marrow production of granulocytes consequent on platelet-associated immunoglobulin testing has not inhibition ofgranulocyte progenitors. Leiderman et al been widely used in high risk patients for reasons of described deficiency of growth of the granulocyte- safety. In patients with reduced platelet numbers and macrophage progenitor cell (CFU-GM) from bone no splenomegaly, no drug treatment, and a marrow marrows of patients with HIV disease and postulated showing plentiful megakaryocytes, a presumptive that a glycoprotein present in the marrow of infected diagnosis ofimmune thrombocytopenia may be made. patients might be the inhibitory agent.' The condition varies in HIV antibody positive Monocytopenia was apparent in 79 (8 6%) of the patients, as in other patients with immune throm- 925 HIV antibody positive patients studied by Cos- bocytopenia, from a well compensated state with only tello and in a higher percentage ofpatients from whom a mild reduction in platelet numbers to a severe marrow aspirates were taken (35% of Treacy's series, condition with very low platelet counts. 43% of Mir's patients). Morphological abnormalities The mechanism for immune thrombocytopenia has of monocytes were observed by Treacy and also by been studied by several workers in the United States. the monocytes vacuol- Walsh et al showed high concentrations of platelet- Spivak,4 showing cytoplasmic http://jcp.bmj.com/ isation and abnormal nuclear features. associated IgG and complement in homosexual Anaemia is commonly seen in patients with patients with idiopathic thrombocytopenia (ITP).'2 AIDS,' 48 often reflecting reticuloendothelial iron These values were around four times higher than those block and effects of treatment with drugs such as seen in classic ITP and it is likely that they reflect co-trimoxazole, pentamidine, foscarnet and more deposition ofimmune complexes on the surface of the recently zidovudine (AZT). Blood transfusion is often platelet. Raised concentrations of immune complexes necessary in patients with AIDS, especially in those are commonly found in patients with HIV disease, and receiving AZT, a drug which produces severe anaemia interestingly, the homosexual control patients with on October 1, 2021 by guest. Protected copyright. in a proportion ofrecipients.9 Forty nine (36%) of 138 normal platelet counts had concentrations ofplatelet- patients treated with AZT at this hospital required associated IgG and complement which were sig- blood transfusion at least once.'" nificantly higher than those of non-homosexual con- Erythroid hypoplasia with severe anaemia has trols, suggesting that immune complex deposition on recently been described in patients with disseminated platelets may occur without large scale platelet des- Mycobacterium avium-intracellulae (MAI) infection." truction. Whether bone marrow stem cells are infected with A true antiplatelet autoantibody, however, may the HIV virus is as yet unknown but Zon suggested coexist with immune complexes on the surface of the that erythropoiesis could be suppressed by the action platelet. Strickler et al reported platelet membrane of the retrovirus on progenitor cell proliferation or antibody in homosexual patients with ITP with reac- maturation.8 Spivak raised the possibility of the tivity against a 25000 molecular weight platelet mem- anaemia in HIV disease being at least partly the result brane antigen, suggesting the presence of a 7S platelet of suppression oferythropoiesis by cell to cell interac- antibody.'3 tion.4 The imbalance ofT helper and T suppressor cell Furthermore, Van der Lelie eluted platelet bound populations in AIDS lends credence to this theory. immunoglobulin from his patients with HIV related Thrombocytopenia is a well recognised occurrence disease that
Load more

Recommended publications
  • My Beloved Neutrophil Dr Boxer 2014 Neutropenia Family Conference
    The Beloved Neutrophil: Its Function in Health and Disease Stem Cell Multipotent Progenitor Myeloid Lymphoid CMP IL-3, SCF, GM-CSF CLP Committed Progenitor MEP GMP GM-CSF, IL-3, SCF EPO TPO G-CSF M-CSF IL-5 IL-3 SCF RBC Platelet Neutrophil Monocyte/ Basophil B-cells Macrophage Eosinophil T-Cells Mast cell NK cells Mature Cell Dendritic cells PRODUCTION AND KINETICS OF NEUTROPHILS CELLS % CELLS TIME Bone Marrow: Myeloblast 1 7 - 9 Mitotic Promyelocyte 4 Days Myelocyte 16 Maturation/ Metamyelocyte 22 3 – 7 Storage Band 30 Days Seg 21 Vascular: Peripheral Blood Seg 2 6 – 12 hours 3 Marginating Pool Apoptosis and ? Tissue clearance by 0 – 3 macrophages days PHAGOCYTOSIS 1. Mobilization 2. Chemotaxis 3. Recognition (Opsonization) 4. Ingestion 5. Degranulation 6. Peroxidation 7. Killing and Digestion 8. Net formation Adhesion: β 2 Integrins ▪ Heterodimer of a and b chain ▪ Tight adhesion, migration, ingestion, co- stimulation of other PMN responses LFA-1 Mac-1 (CR3) p150,95 a2b2 a CD11a CD11b CD11c CD11d b CD18 CD18 CD18 CD18 Cells All PMN, Dendritic Mac, mono, leukocytes mono/mac, PMN, T cell LGL Ligands ICAMs ICAM-1 C3bi, ICAM-3, C3bi other other Fibrinogen other GRANULOCYTE CHEMOATTRACTANTS Chemoattractants Source Activators Lipids PAF Neutrophils C5a, LPS, FMLP Endothelium LTB4 Neutrophils FMLP, C5a, LPS Chemokines (a) IL-8 Monocytes, endothelium LPS, IL-1, TNF, IL-3 other cells Gro a, b, g Monocytes, endothelium IL-1, TNF other cells NAP-2 Activated platelets Platelet activation Others FMLP Bacteria C5a Activation of complement Other Important Receptors on PMNs ñ Pattern recognition receptors – Detect microbes - Toll receptor family - Mannose receptor - bGlucan receptor – fungal cell walls ñ Cytokine receptors – enhance PMN function - G-CSF, GM-CSF - TNF Receptor ñ Opsonin receptors – trigger phagocytosis - FcgRI, II, III - Complement receptors – ñ Mac1/CR3 (CD11b/CD18) – C3bi ñ CR-1 – C3b, C4b, C3bi, C1q, Mannose binding protein From JG Hirsch, J Exp Med 116:827, 1962, with permission.
    [Show full text]
  • Practice Parameter for the Diagnosis and Management of Primary Immunodeficiency
    Practice parameter Practice parameter for the diagnosis and management of primary immunodeficiency Francisco A. Bonilla, MD, PhD, David A. Khan, MD, Zuhair K. Ballas, MD, Javier Chinen, MD, PhD, Michael M. Frank, MD, Joyce T. Hsu, MD, Michael Keller, MD, Lisa J. Kobrynski, MD, Hirsh D. Komarow, MD, Bruce Mazer, MD, Robert P. Nelson, Jr, MD, Jordan S. Orange, MD, PhD, John M. Routes, MD, William T. Shearer, MD, PhD, Ricardo U. Sorensen, MD, James W. Verbsky, MD, PhD, David I. Bernstein, MD, Joann Blessing-Moore, MD, David Lang, MD, Richard A. Nicklas, MD, John Oppenheimer, MD, Jay M. Portnoy, MD, Christopher R. Randolph, MD, Diane Schuller, MD, Sheldon L. Spector, MD, Stephen Tilles, MD, Dana Wallace, MD Chief Editor: Francisco A. Bonilla, MD, PhD Co-Editor: David A. Khan, MD Members of the Joint Task Force on Practice Parameters: David I. Bernstein, MD, Joann Blessing-Moore, MD, David Khan, MD, David Lang, MD, Richard A. Nicklas, MD, John Oppenheimer, MD, Jay M. Portnoy, MD, Christopher R. Randolph, MD, Diane Schuller, MD, Sheldon L. Spector, MD, Stephen Tilles, MD, Dana Wallace, MD Primary Immunodeficiency Workgroup: Chairman: Francisco A. Bonilla, MD, PhD Members: Zuhair K. Ballas, MD, Javier Chinen, MD, PhD, Michael M. Frank, MD, Joyce T. Hsu, MD, Michael Keller, MD, Lisa J. Kobrynski, MD, Hirsh D. Komarow, MD, Bruce Mazer, MD, Robert P. Nelson, Jr, MD, Jordan S. Orange, MD, PhD, John M. Routes, MD, William T. Shearer, MD, PhD, Ricardo U. Sorensen, MD, James W. Verbsky, MD, PhD GlaxoSmithKline, Merck, and Aerocrine; has received payment for lectures from Genentech/ These parameters were developed by the Joint Task Force on Practice Parameters, representing Novartis, GlaxoSmithKline, and Merck; and has received research support from Genentech/ the American Academy of Allergy, Asthma & Immunology; the American College of Novartis and Merck.
    [Show full text]
  • Complete Blood Count in Primary Care
    Complete Blood Count in Primary Care bpac nz better medicine Editorial Team bpacnz Tony Fraser 10 George Street Professor Murray Tilyard PO Box 6032, Dunedin Clinical Advisory Group phone 03 477 5418 Dr Dave Colquhoun Michele Cray free fax 0800 bpac nz Dr Rosemary Ikram www.bpac.org.nz Dr Peter Jensen Dr Cam Kyle Dr Chris Leathart Dr Lynn McBain Associate Professor Jim Reid Dr David Reith Professor Murray Tilyard Programme Development Team Noni Allison Rachael Clarke Rebecca Didham Terry Ehau Peter Ellison Dr Malcolm Kendall-Smith Dr Anne Marie Tangney Dr Trevor Walker Dr Sharyn Willis Dave Woods Report Development Team Justine Broadley Todd Gillies Lana Johnson Web Gordon Smith Design Michael Crawford Management and Administration Kaye Baldwin Tony Fraser Kyla Letman Professor Murray Tilyard Distribution Zane Lindon Lyn Thomlinson Colleen Witchall All information is intended for use by competent health care professionals and should be utilised in conjunction with © May 2008 pertinent clinical data. Contents Key points/purpose 2 Introduction 2 Background ▪ Haematopoiesis - Cell development 3 ▪ Limitations of reference ranges for the CBC 4 ▪ Borderline abnormal results must be interpreted in clinical context 4 ▪ History and clinical examination 4 White Cells ▪ Neutrophils 5 ▪ Lymphocytes 9 ▪ Monocytes 11 ▪ Basophils 12 ▪ Eosinophils 12 ▪ Platelets 13 Haemoglobin and red cell indices ▪ Low haemoglobin 15 ▪ Microcytic anaemia 15 ▪ Normocytic anaemia 16 ▪ Macrocytic anaemia 17 ▪ High haemoglobin 17 ▪ Other red cell indices 18 Summary Table 19 Glossary 20 This resource is a consensus document, developed with haematology and general practice input. We would like to thank: Dr Liam Fernyhough, Haematologist, Canterbury Health Laboratories Dr Chris Leathart, GP, Christchurch Dr Edward Theakston, Haematologist, Diagnostic Medlab Ltd We would like to acknowledge their advice, expertise and valuable feedback on this document.
    [Show full text]
  • University of Birmingham the Primary Immunodeficiency Disorders
    University of Birmingham The primary immunodeficiency disorders Shields, Adrian; Patel, Smita Y DOI: 10.1016/j.mpmed.2017.07.011 License: Creative Commons: Attribution-NonCommercial-NoDerivs (CC BY-NC-ND) Document Version Peer reviewed version Citation for published version (Harvard): Shields, A & Patel, SY 2017, 'The primary immunodeficiency disorders', Medicine, vol. 45, no. 10, pp. 597-604. https://doi.org/10.1016/j.mpmed.2017.07.011 Link to publication on Research at Birmingham portal Publisher Rights Statement: Shields, A. Patel, S. (2017) The primary immunodeficiency disorders, Medicine, volume 45, issue 10, pages 597-604, https://doi.org/10.1016/j.mpmed.2017.07.011 General rights Unless a licence is specified above, all rights (including copyright and moral rights) in this document are retained by the authors and/or the copyright holders. The express permission of the copyright holder must be obtained for any use of this material other than for purposes permitted by law. •Users may freely distribute the URL that is used to identify this publication. •Users may download and/or print one copy of the publication from the University of Birmingham research portal for the purpose of private study or non-commercial research. •User may use extracts from the document in line with the concept of ‘fair dealing’ under the Copyright, Designs and Patents Act 1988 (?) •Users may not further distribute the material nor use it for the purposes of commercial gain. Where a licence is displayed above, please note the terms and conditions of the licence govern your use of this document. When citing, please reference the published version.
    [Show full text]
  • ESID Registry – Working Definitions for Clinical Diagnosis of PID
    ESID Registry – Working Definitions for Clinical Diagnosis of PID These criteria are only for patients with no genetic diagnosis*. *Exceptions: Atypical SCID, DiGeorge syndrome – a known genetic defect and confirmation of criteria is mandatory Available entries (Please click on an entry to see the criteria.) Page Acquired angioedema .................................................................................................................................................................. 4 Agammaglobulinaemia ................................................................................................................................................................ 4 Asplenia syndrome (Ivemark syndrome) ................................................................................................................................... 4 Ataxia telangiectasia (ATM) ......................................................................................................................................................... 4 Atypical Severe Combined Immunodeficiency (Atypical SCID) ............................................................................................... 5 Autoimmune lymphoproliferative syndrome (ALPS) ................................................................................................................ 5 APECED / APS1 with CMC - Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) .................. 5 Barth syndrome ...........................................................................................................................................................................
    [Show full text]
  • Practice Parameter for the Diagnosis and Management of Primary Immunodeficiency Francisco A
    Practice parameter Practice parameter for the diagnosis and management of primary immunodeficiency Francisco A. Bonilla, MD, PhD*; I. Leonard Bernstein, MD†; David A. Khan, MD‡; Zuhair K. Ballas, MD§; Javier Chinen, MD, PhD¶; Michael M. Frank, MDʈ; Lisa J. Kobrynski, MD**; Arnold I. Levinson, MD††; Bruce Mazer, MD‡‡; Robert P. Nelson, Jr, MD§§; Jordan S. Orange, MD, PhD¶¶; John M. Routes, MDʈʈ; William T. Shearer, MD, PhD***; and Ricardo U. Sorensen, MD††† TABLE OF CONTENTS I. Preface....................................................................................................................................................................................S1 II. Executive Summary...............................................................................................................................................................S2 III. Algorithms .............................................................................................................................................................................S7 IV. Summary Statements ...........................................................................................................................................................S14 V. General Considerations........................................................................................................................................................S20 VI. Humoral Immunodeficiencies .............................................................................................................................................S24
    [Show full text]
  • Blueprint Genetics Primary Immunodeficiency Panel
    Primary Immunodeficiency Panel Test code: IM0301 Is a 298 gene panel that includes assessment of non-coding variants. Is ideal for patients with a clinical suspicion of any type of primary immunodeficiency (PID). About Primary Immunodeficiency Primary immunodeficiencies (PIDs) are a genetically heterogeneous group of diseases. The International Union of Immunological Societies Expert Committee categorizes PIDs into nine different categories: 1) combined immunodeficiencies, 2) combined immunodeficiencies with associated or syndromic features, 3) predominantly antibody deficiencies, 4) diseases of immune dysregulation, 5) congenital defects of phagocyte number, function, or both, 6) defects in intrinsic and innate immunity, 7) autoinflammatory disorders, 8) complement deficiencies and 9) phenocopies of PIDs. Despite a heterogeneous genetic basis, the core symptoms are often very similar complicating the diagnosis. In addition, many PIDs may be included in more than one category. Treatment choice without knowing the specific mutation in the causative gene may therefore be complicated. Also, type and site of and specific organisms causing the infections may help to classify the disease. In addition to immune-related symptoms, many PIDs have non-immune manifestations. The prevalence of individual PIDs have a wide range, but the combined prevalence of all primary immunodeficiencies is reported to be as high as 5-8:10,000. Some recently identified PIDs are extremely rare. Availability 4 weeks Gene Set Description Genes in the Primary Immunodeficiency
    [Show full text]
  • Clozapine-Induced Late Agranulocytosis and Severe
    Hindawi Publishing Corporation Case Reports in Medicine Volume 2015, Article ID 703218, 7 pages http://dx.doi.org/10.1155/2015/703218 Case Report Clozapine-Induced Late Agranulocytosis and Severe Neutropenia Complicated with Streptococcus pneumonia, Venous Thromboembolism, and Allergic Vasculitis in Treatment-Resistant Female Psychosis Christina Voulgari,1 Raphael Giannas,1 Georgios Paterakis,2 Anna Kanellou,1 Nikolaos Anagnostopoulos,3 and Stamata Pagoni1 1 3rd Department of Internal Medicine, Athens General Regional Hospital “G. Gennimatas”, Mesogeion Avenue 154, 11527Athens,Greece 2Flow Cytometry Laboratory, Department of Immunology, Athens General Regional Hospital “G. Gennimatas”, Athens, Greece 3Department of Hematology, Athens General Regional Hospital “G. Gennimatas”, Athens, Greece Correspondence should be addressed to Christina Voulgari; c v [email protected] Received 10 November 2014; Accepted 27 January 2015 Academic Editor: B. Carpiniello Copyright © 2015 Christina Voulgari et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Clozapine is a second-generation antipsychotic agent from the benzodiazepine group indicated for treatment-resistant schizophre- nia and other psychotic conditions. Using clozapine earlier on once a case appears to be refractory limits both social and personal morbidity of chronic psychosis. However treatment with second-generation antipsychotics is often complicated by adverse effects. We present a case of a 33-year-old Caucasian woman with a 25-year history of refractory psychotic mania after switching to a 2-year clozapine therapy. She presented clozapine-induced absolute neutropenia, agranulocytosis, which were complicated by Streptococcus pneumonia and sepsis.
    [Show full text]
  • The Full Blood Count Blood Test for Colorectal Cancer Detection: a Systematic Review, Meta-Analysis, and Critical Appraisal
    Review The Full Blood Count Blood Test for Colorectal Cancer Detection: A Systematic Review, Meta-Analysis, and Critical Appraisal Pradeep S. Virdee, Ioana Marian, Anita Mansouri, Leena Elhussein, Shona Kirtley, Tim Holt and Jacqueline Birks 1. Description of the full blood count Table S1. Description of each component of the full blood count blood test Full blood count Conventional Description/purpose component units The number of red blood cells in the blood. 1012 per litre Lower levels can be associated with blood less. Red blood cell count 1 (1012/L) Each red blood cell contains levels of haemoglobin. The number of white blood cells in the blood. White blood cell count 1 109 per litre (109/L) They are of the immune system and involved in protecting the body against disease. Grams per Carries oxygen around the body and is found in Haemoglobin 1 decilitre (g/dL) red blood cells Haematocrit/packed cell Percentage, i.e. as Proportion of blood that is occupied by the red volume 2 litres per litre (%) cells. A possible alternative for detecting anaemia. Average size of red blood cells. Calculated as Mean corpuscular Femtolitre (f/L) haematocrit (%) divided by the number of red volume 2 blood cells (1012/L) Average of amount of haemoglobin that is in each Mean corpuscular Pictograms (pg) red blood cell. Calculated as haemoglobin (g/dL) haemoglobin 2 divided by the red blood cell count (1012/L) Average of amount of haemoglobin in individual Mean corpuscular Grams per cells based on the volume of red blood cells. haemoglobin decilitre (g/dL) Calculated as haemoglobin (g/dL) divided by the concentration 2 haematocrit (%) Red cell distribution A coefficient, as A measure of the amount of variation in the size width 2 opposed to count of red cells; the higher, the more variation.
    [Show full text]
  • Defective Leukocyte Adhesion and Chemotaxis Contributes to Combined Immunodeficiency in Humans with Autosomal Recessive MST1 Deficiency
    J Clin Immunol (2016) 36:117–122 DOI 10.1007/s10875-016-0232-2 ASTUTE CLINICIAN REPORT Defective Leukocyte Adhesion and Chemotaxis Contributes to Combined Immunodeficiency in Humans with Autosomal Recessive MST1 Deficiency Tarana Singh Dang 1 & Joseph DP Willet1 & Helen R Griffin2 & Neil V Morgan3 & Graeme O’Boyle1 & Peter D Arkwright4 & Stephen M Hughes4 & Mario Abinun1,5 & Louise J Tee3 & Dawn Barge6 & Karin R Engelhardt1 & Michael Jackson5 & Andrew J Cant1,5 & Eamonn R Maher3,7 & Mauro Santibanez Koref2 & Louise N Reynard1 & Simi Ali1 & Sophie Hambleton1,5 Received: 20 March 2015 /Accepted: 4 January 2016 /Published online: 22 January 2016 # The Author(s) 2016. This article is published with open access at Springerlink.com Abstract measured, and transwell assays were used to assess chemo- Purpose To investigate the clinical and functional aspects of taxis. Chemokine receptor expression was examined by flow MST1 (STK4) deficiency in a profoundly CD4-lymphopenic cytometry and receptor signalling by immunoblotting. kindred with a novel homozygous nonsense mutation in Results A homozygous nonsense mutation in STK4 STK4. Although recent studies have described the cellular (c.442C > T, p.Arg148Stop) was found in the patients, leading effects of murine Mst1 deficiency, the phenotype of MST1- to a lack of MST1 protein expression. Patient leukocytes ex- deficient human lymphocytes has yet to be fully explored. hibited deficient chemotaxis after stimulation with CXCL11, Patient lymphocytes were therefore investigated in the context despite preserved expression of CXCR3. Patient lymphocytes of current knowledge of murine Mst1 deficiency. were also unable to bind effectively to immobilised ICAM-1 Methods Genetic etiology was identified by whole exome se- under flow conditions, in keeping with a failure to develop quencing of genomic DNA from two siblings, combined with high affinity binding.
    [Show full text]
  • Congenital Neutropenia and Primary Immunodeficiency Diseases
    Critical Reviews in Oncology / Hematology 133 (2019) 149–162 Contents lists available at ScienceDirect Critical Reviews in Oncology / Hematology journal homepage: www.elsevier.com/locate/critrevonc Congenital neutropenia and primary immunodeficiency diseases T ⁎ Jonathan Spoora,b,c, Hamid Farajifarda,d, Nima Rezaeia,d,e, a Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran,Iran b Erasmus University Medical Centre, Erasmus University Rotterdam, Rotterdam, the Netherlands c Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Rotterdam, the Netherlands d Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran e Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran ARTICLE INFO ABSTRACT Keywords: Neutropenia is a dangerous and potentially fatal condition that renders patients vulnerable to recurrent infec- Neutropenia tions. Its severity is commensurate with the absolute count of neutrophil granulocytes in the circulation. In Congenital paediatric patients, neutropenia can have many different aetiologies. Primary causes make up but asmall Immunological deficiency syndromes portion of the whole and are relatively unknown. In the past decades, a number of genes has been discovered Genetic diseases that are responsible for congenital neutropenia. By perturbation of mitochondrial energy metabolism, vesicle trafficking or synthesis of functional proteins, these mutations cause a maturation arrest in myeloid precursor cells in the bone marrow. Apart from these isolated forms, congenital neutropenia is associated with a multi- plicity of syndromic diseases that includes among others: oculocutaneous albinism, metabolic diseases and bone marrow failure syndromes.
    [Show full text]
  • Leukocytosis Associated with Clozapine Treatment: a Case Series and Systematic Review of the Literature
    medicina Review Leukocytosis Associated with Clozapine Treatment: A Case Series and Systematic Review of the Literature Pasquale Paribello 1,2,† , Mirko Manchia 1,2,3,† , Massimo Zedda 1 , Federica Pinna 1,2,* and Bernardo Carpiniello 1,2 1 Section of Psychiatry, Department of Medical Sciences and Public Health, University of Cagliari, 09124 Cagliari, Italy; [email protected] (P.P.); [email protected] (M.M.); [email protected] (M.Z.); [email protected] (B.C.) 2 Unit of Clinical Psychiatry, University Hospital Agency of Cagliari, 09124 Cagliari, Italy 3 Department of Pharmacology, Dalhousie University, Halifax, NS B3H 4R2, Canada * Correspondence: [email protected] † These authors contributed equally. Abstract: Background and Objectives: Clozapine is the only antipsychotic approved for treatment- resistant schizophrenia. Despite its superior efficacy profile as compared with other antipsychotics, clozapine remains underutilized. Clozapine monitoring systems clearly describe the proposed management of clozapine-induced neutropenia; however, no specific mention is made of how to interpret neutrophilic leukocytosis, despite that being a relatively frequent finding. Prescribers unfamiliar with this molecule may misjudge its clinical significance, potentially leading to untimely treatment interruption. Here, we systematically review the literature on the risk of neutrophilic leukocytosis during clozapine treatment, and describe eight additional cases among our patient cohort. Materials and Methods: We performed a systematic review of the literature on PubMed and Embase using the PRISMA 2020 guidelines, and selected all original reports describing either (1) the prevalence of neutrophilic leukocytosis during clozapine treatment, or (2) the clinical significance of Citation: Paribello, P.; Manchia, M.; Zedda, M.; Pinna, F.; Carpiniello, B. neutrophilic leukocytosis. We described eight additional cases of neutrophilic leukocytosis during Leukocytosis Associated with clozapine treatment while attending an outpatient psychiatric clinic.
    [Show full text]