MENU
WORLDALLERGY.ORG
Facebook: World Allergy Organization
Twitter: World Allergy Organization
LinkedIn: World Allergy Organization
Instagram: World Allergy Organization
Back to Top

Article Summaries - February 2014

CD8+ T CELLS PRODUCING IL-3 AND IL-5 IN NON-IGE-MEDIATED EOSINOPHILIC DISEASES

(Stoeckle C, Simon H-U. Allergy 2013; 68: 1622–1625)

  • IL-5, IL-3, GM-CSF (eosinophil hematopoietins): (i) crucial cytokines for eosinophil development, survival and function; (ii) activated CD4+ Th2 cells have been considered as the main source; (iii) CD8+ T cells can be an important source (Tc2 population).
  • Eosinophils: (i) multifunctional effector cells; (ii) normal blood counts: <500 cells/ìL (eosinophilia: >500 cells/ìL; hypereosinophilia: >1500 cells/ìL).
  • Causes of blood eosinophilia: helminthic infections, allergic diseases (e.g. atopic dermatitis, asthma, rhinosinusitis, eosinophilic esophagitis), paraneoplastic eosinophilia, hypereosinophilic syndromes, immune dysregulation.

DOWNREGULATION OF POLYMERIC IMMUNOGLOBULIN RECEPTOR AND SECRETORY IGA ANTIBODIES IN EOSINOPHILIC UPPER AIRWAY DISEASES

(Hupin C, Rombaux P, Bowen H, Gould H, Lecocq M, Pilette C. Allergy 2013; 68: 1589–1597)

  • Rhinosinusitis (RS): inflammation of nasal and paranasal mucosa; acute RS: <12 wks; chronic RS (CRS): ≥12 wks.
  • Diagnosis of CRS: (i) nasal blockage or nasal discharge (anterior or posterior) + facial pain/pressure or hyposmia, (ii) objective clinical, endoscopic or radiologic evidence of sinonasal inflammation (e.g. polyps, mucopurulent discharge, edema).
  • Pathogenesis of CRS: (i) Anatomic/structural problems: nasal septal deviation, nasal valve dysfunction, concha bullosa (enlarged nasal turbinate caused by internal ethmoid air cell), adenoid hyperplasia (mainly in children), nasal choanal narrowing, nasal or sinus mucoceles, scarring from prior nasal or sinus surgery, septal perforations, nasal foreign body, malignancies.
  • (ii) Altered immunity: altered epithelial barrier (↓ epithelial tight junctions [occludins, claudins, etc], ↑ epitelial shedding, ↓ repairing proteins [psoriasin, calgranulin A and B, SPINK5]); ↓ ciliary clearance (cystic fibrosis, primary ciliary dyskinesia); ↓ antimicrobial peptides (defensins, psoriasin, PLUNC family, lysozyme, lactoferrin); ↓ TLR responses (especially TLR2 and TLR9); ↓ STAT3 function; ↑ immune activation (T-cell responses [TH2, TH17, TH22], IgE, IgA, effector cells [mast cells, eosinophils], autoantibodies, IL-32); immunodeficiencies (eg. agammaglobulinemia); inflammatory diseases (eg. Wegener’s granulomatosis, sarcoidosis, aspirin-exacerbated respiratory disease); ↑ remodeling (TGF-â, MMPs, TIMPs).
  • (iii) Infections (bacteria, fungi, virus, biofilms): role is not fully defined → antibiotics may help (macrolides and doxycycline have been suggested due to antibacterial and antiinflammatory properties); biofilm-destabilizing agents may help; some patients respond to antifungals.
  • (iv) Pollutants and drugs: cigarette smoke, pollutants, cocaine, topical vasoconstrictors.
  • CRS phenotypes: (i) CRS with nasal polyps (CRSwNP): 4% of the population, TH2 environment (eosinophilic inflammation), better response to intranasal corticosteroids; (ii) CRS without nasal polyps (CRSsNP): ↑ remodeling (TGF-â, MMP, TIMP, collagen), predominance of neutrophils.
  • Possible CRS endotypes: (i) fungal-induced endotype (eg. allergic fungal RS); (ii) S. aureus-induced endotype (superantigens favor TH2 milieu; IL-4 and IL-13 ↓ immunity to S aureus); (iii) mucosal barrier defect endotype; (iv) innate immune defect endotype; (v) TH2/IgE/eosinophilic endotype; (vi) TH17/neutrophilic endotype; (vii) autoimmune endotype; (viii) drug-induced endotype (eg. AERD); (ix) remodeling endotype.
  • Treatment of CRS: (i) nasal irrigation/douching; (ii) intranasal and oral corticosteroids; (iii) antibiotics; (iv) surgery; (v) other therapies: antihistamines, LTRA, 5-lipoxygenase inhibitors, allergen immunotherapy, biological agents (monoclonal antibodies, soluble receptors, cytokines), aspirin desensitization, topical and oral antifungals, decongestants, mucolytics (eg. n-acetylcysteine), phototherapy, MTX, protein pump inhibitors, capsaicin, furosemide, vit D, Manuka honey, bromelain, quercetin, undecylenic acid, urtica dioica, massage of the sinus ostea with swabs of botanical essential oils, air purifiers, diets.
  • ‘Futuristic’ therapy of CRS: determine specific CRS phenotypes and endotypes using clinical, laboratory, histologic and genetic biomarkersindividualize therapy.
  • Immunoglobulin A (IgA): (i) 1st-line defence mechanism in mucosas; (ii) main function: neutralization of pathogens and hazardous particles; (iii) origin: mucosal plasma cells produce IgA dimers → epithelial cells transport IgA dimers into mucosal secretions (GI mucosa, urogenital mucosa, respiratory mucosa, tears, saliva, breast milk) using the polymeric immunoglobulin receptor (pIgR).
  • Authors show ↓ pIgR expression in patients with chronic upper airway diseases (CRSwNP, CRSsNP, allergic rhinitis) ↓ secretory IgA in nasal secretions, ↑ subepithelial IgA ↑ susceptibility to respiratory infections, ↑ eosinophilic inflammation.
  • Other diseases that may present ↓ local pIgR expression: severe COPD, lung cancer, nasopharyngeal cancer.

THE HISTORY OF MAST CELL AND BASOPHIL RESEARCH – SOME LESSONS LEARNT FROM THE LAST CENTURY

(Blank U, Falcone FH, Nilsson G. Allergy 2013; 68: 1093–1101)

  • 1863 → Friedrich von Recklinghausen described mast cells as ‘granulated cells in connective tissues’.
  • 1878 → Paul Ehrlich coined the term ‘mast cells’ (due to their appearance of ‘having ingested large amounts of nutrients’).
  • 1879 → Paul Ehrlich described basophils.
  • 1902 → Paul Portier and Charles Richet described the phenomenon of anaphylaxis (from the Greek ana = against and phylaxis = protection).
  • 1903 → Maurice Arthus described the Arthus phenomenon (repeated subcutaneous injections of the same horse antiserum caused local inflammation and necrosis due to hypersensitivity).
  • 1906 → Clemens von Pirquet described the term ‘allergy’ (from the Greek allos = other and ergon = work, reaction).
  • 1921 → Carl Prausnitz and Heinz Küstner described the Prausnitz–Küstner (PK) reaction: ‘allergy can be transferred by transferring serum from the allergic subject to a healthy person’ (this discovery ended the belief that an anaphylactic/allergic reaction was caused by poisons).
  • 1968 → IgE was considered as the 5th type of immunoglobulin.
  • Mast cells and basophils: (i) originate from HSCs; (ii) can de novo synthesize and secrete >30 cytokines; (iii) can also preform and store cytokines (e.g. TNF, IL-4); (iv) mast cells, but not basophils, can synthesize PGD2; (v) cytokine spectrum appears to be more TH2-restricted for basophils; (vi) in humans, IL-3 gives rise to basophils and not mast cells (in contrast to mouse); (vii) 2 subtypes of mast cells in humans: mast cells that contain only tryptase (MCT) [correspond in part to the mucosal type of mouse mast cells] and mast cells that contain both tryptase and chymase (MCTC) [correspond to the connective tissue type of mouse mast cells]; (viii) mast cells can either be pro-inflammatory, anti-inflammatory or immunosuppressive.
  • Functions of mast cells and basophils (some are better established than others): (i) defense against ticks (e.g. histamine promotes scratching and tick removal); (ii) defense against helminths (helminths are the most potent inducers of IgE responses); (iii) contribution to defense against some fungi, bacteria and virus; (iv) inflammation (e.g. activation by pathogen or danger signals through PRRs); (v) tissue remodeling and repair; (vi) protection against foreign agents (e.g. mast cell-derived proteases degrade exogenous toxins [venoms] or endogenous molecules [endothelin-1 and VIP]); (vii) angiogenesis; (viii) tumor immunity.

ROLE OF THE BASOPHIL ACTIVATION TEST IN THE DIAGNOSIS OF LOCAL ALLERGIC RHINITIS

(Gómez E, Campo P, Rondón C, Barrionuevo E, Blanca-López E, Torres MJ, Herrera R, Galindo L, Mayorga C, Blanca M. J Allergy Clin Immunol 2013; 132: 975-976)

  • Local allergic rhinitis (LAR, ‘entopy’): local production of allergen-specific IgE (sIgE), negative detection of sIgE by skin and serum tests (absence of systemic atopy); prevalence: 25% of all rhinitis cases (usually misdiagnosed as nonallergic rhinitis); diagnosis: nasal provocation tests (advantages: high sensitivity and specificity, very reproducible; limitations: requires well-trained personnel, time consuming), measurement of sIgE in nasal secretion (advantages: noninvasive, very specific; limitation: low sensitivity).
  • Basophil activation test (BAT): validated technique for in vitro diagnosis of sensitization to aeroallergens, food allergens, Hymenoptera venom and several drugs.
  • Authors show in this pilot study that BAT might be a useful test to diagnose LAR caused by Dermatophagoides pteronyssinus.
  • Important points: (i) BAT could diagnose at least 50% of patients with LAR to D pteronyssinus; (ii) BAT could detect sIgE on blood basophils from LAR patients; (iii) after local production of sIgE, basophils might be the first or only target cells before the detection of sIgE in serum and skin; (iv) advantages of BAT: higher sensitivity than nasal sIgE detection, less time-consuming than nasal provocation test.