DOCSLIB.ORG

Complement Components C3 and C4 Indicate Vasculitis Manifestations to Distinct Renal Compartments in ANCA-Associated Glomerulonephritis

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Complement Components C3 and C4 Indicate Vasculitis Manifestations to Distinct Renal Compartments in ANCA-Associated Glomerulonephritis International Journal of Molecular Sciences Article Complement Components C3 and C4 Indicate Vasculitis Manifestations to Distinct Renal Compartments in ANCA-Associated Glomerulonephritis Samy Hakroush 1 ,Désirée Tampe 2, Peter Korsten 2 , Philipp Ströbel 1 and Björn Tampe 2,* 1 Institute of Pathology, University Medical Center Göttingen, 37075 Göttingen, Germany; [email protected] (S.H.); [email protected] (P.S.) 2 Department of Nephrology and Rheumatology, University Medical Center Göttingen, 37075 Göttingen, Germany; [email protected] (D.T.); [email protected] (P.K.) * Correspondence: [email protected]; Tel.: +49-551-39-10575 Abstract: Acute kidney injury (AKI) is a common and severe complication of antineutrophil cyto- plasmic antibodies (ANCA)-associated vasculitis (AAV) causing progressive chronic kidney disease (CKD), end-stage renal disease (ESRD) or death. Pathogenic ANCAs, in particular proteinase 3 (PR3) and myeloperoxidase (MPO), trigger a deleterious immune response resulting in pauci-immune necrotizing and crescentic glomerulonephritis (GN), a common manifestation of glomerular injury in AAV. However, there is growing evidence that activation of the complement pathway contributes to the pathogenesis and progression of AAV. We here aimed to compare glomerular and tubuloin- Citation: Hakroush, S.; Tampe, D.; terstitial lesions in ANCA GN and extrarenal manifestation of AAV in association with levels of Korsten, P.; Ströbel, P.; Tampe, B. circulating complement components C3c and C4. Methods: Plasma levels of C3c and C4 in a total Complement Components C3 and C4 number of 53 kidney biopsies with ANCA GN were retrospectively included between 2015 and 2020. Indicate Vasculitis Manifestations to Glomerular and tubulointerstitial lesions were evaluated according to established scoring systems for Distinct Renal Compartments in ANCA GN and analogous to the Banff classification. Results: We here show that circulating levels of ANCA-Associated C3c and C4 in ANCA GN were comparable to the majority of other renal pathologies. Furthermore, Glomerulonephritis. Int. J. Mol. Sci. hypocomplementemia was only detectable in a minor subset of ANCA GN and not correlated with 2021, 22, 6588. https://doi.org/ renal or extrarenal AAV manifestations. However, low levels of circulating C3c correlated with AKI 10.3390/ijms22126588 severity in ANCA GN independent of systemic disease activity or extrarenal AAV manifestation. By Academic Editors: Amandeep Bajwa systematic scoring of glomerular and tubulointerstitial lesions, we provide evidence that low levels and Navjot Pabla of circulating C3c and C4 correlated with vasculitis manifestations to distinct renal compartments in ANCA GN. Conclusions: We here expand our current knowledge about distinct complement Received: 25 May 2021 components in association with vasculitis manifestations to different renal compartments in ANCA Accepted: 16 June 2021 GN. While low levels of C4 correlated with glomerulitis, our observation that low levels of circulating Published: 19 June 2021 complement component C3c is associated with interstitial vasculitis manifestation reflected by intimal arteritis implicates that C3c contributes to tubulointerstitial injury in ANCA GN. Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in Keywords: acute kidney injury; innate immunity; complement system activation; autoimmune published maps and institutional affil- diseases; systemic vasculitis; ANCA-associated glomerulonephritis iations. 1. Introduction Copyright: © 2021 by the authors. According to the 2012 revised Chapel Hill Consensus Conference Nomenclature of Licensee MDPI, Basel, Switzerland. Vasculitides, antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is This article is an open access article a small vessel vasculitis, most frequently presenting as microscopic polyangiitis (MPA) distributed under the terms and or granulomatosis with polyangiitis (GPA) [1,2]. Acute kidney injury (AKI) is a common conditions of the Creative Commons Attribution (CC BY) license (https:// and severe complication of AAV as it can cause progressive chronic kidney disease (CKD), creativecommons.org/licenses/by/ end-stage renal disease (ESRD) or death [3,4]. Pathogenic ANCAs, in particular proteinase 4.0/). 3 (PR3) and myeloperoxidase (MPO), trigger a deleterious immune response resulting in Int. J. Mol. Sci. 2021, 22, 6588. https://doi.org/10.3390/ijms22126588 https://www.mdpi.com/journal/ijms Int. J. Mol. Sci. 2021, 22, 6588 2 of 15 Int. J. Mol. Sci. 2021, 22, x FOR PEER REVIEW 2 of 16 pauci-immune necrotizing and crescentic glomerulonephritis (GN), a common manifesta- tion of glomerular injury in AAV [5]. Several studies have investigated determinants of 3 (PR3) and myeloperoxidase (MPO), trigger a deleterious immune response resulting in renalpauci-immune outcome necrotizing in ANCA GN,and crescentic including glomerulonephritis baseline kidney function(GN), a common and histopathological manifes- lesionstation of [ 6glomerular,7]. On a injury mechanistic in AAV level,[5]. Several neutrophils studies have are activated investigated by determinants pathogenic ANCAsof causingrenal outcome release in of ANCA inflammatory GN, including cytokines, baseline reactive kidney oxygen function species and andhistopathological lytic enzymes, and resultinglesions [6,7]. in excessive On a mechanistic formation level, of neutrophil neutrophils extracellular are activated traps by (NETs)pathogenic [8– 10ANCAs]. At least in part,causing these release mechanisms of inflammatory underly cytokines, the pathogenicity reactive oxygen of ANCAs species mediating and lytic enzymes, inflammation and and vascularresulting injury.in excessive Disease formation manifestations of neutrophil in the extracellular kidney are traps usually (NETs) characterized [8–10]. At byleast a pauci- immunityin part, these with mechanisms only minor, underly if any, the immunoglobulin pathogenicity of ANCAs and complement mediating inflammation deposition in the vascularand vascular system. injury. In general,Disease manifestations circulating complement in the kidney components are usually C3 characterized and C4 levels by a in AAV arepauci-immunity normal [11]. with However, only minor, there if isany, growing immunoglobulin evidence and that complement activation of deposition the complement in pathwaythe vascular contributes system. In to general, the pathogenesis circulating andcomplement progression components of AAV C3 [12 and–14]. C4 In levels experimental in models,AAV are pauci-immunenormal [11]. However, crescentic there GN is growing correlated evidence with thethat activationactivation of of the the comple- complement systemment pathway [15]. Furthermore, contributes to blocking the pathogenes the alternativeis and progression complement of AAV system [12–14]. resulted In exper- in protec- tionimental from models, crescentic pauci-immune GN, further crescentic supporting GN correlated an important with contributionthe activation ofof thethe alternativecom- complementplement system system [15]. Furthermore, in the pathogenesis blocking of the ANCA alternative GN [ 15complement]. Conversely, system complement resulted C4d in protection from crescentic GN, further supporting an important contribution of the al- has been found in the majority of renal biopsies, implicating that activation of the classical ternative complement system in the pathogenesis of ANCA GN [15]. Conversely, comple- complement system is also relevant in ANCA GN [16]. The mechanistic contribution of the ment C4d has been found in the majority of renal biopsies, implicating that activation of complement system in the pathogenesis of AAV was further substantiated by recent studies the classical complement system is also relevant in ANCA GN [16]. The mechanistic con- thattribution analyzed of the complementcomplement system components in the pathogenesis in different of activity AAV was states further of AAV substantiated [16–22]. This is especiallyby recent studies relevant that since analyzed the use complement of the anti-C5a components receptor in inhibitor different avacopanactivity states has of recently beenAAV shown[16–22]. to This sustain is especially effective relevant remission since in the AAV, use furtherof the anti-C5a supporting receptor the inhibitor importance of theavacopan complement has recently system been in shown the pathogenesis to sustain effective and progressionremission in AAV, of AAV further [23– support-25]. However, systematicing the importance analysis of the activationcomplement of system the complement in the pathogenesis system in and association progression with of distinct clinicalAAV [23–25]. and histopathological However, systematic lesions analysis in ANCAof the activation GN remains of the elusive.complement Therefore, system in we here aimedassociation to compare with distinct glomerular clinical and and histopathological tubulointerstitial lesions lesions in ANCA in ANCA GN remains GN analogous elu- to thesive. Banff Therefore, classification we here andaimed extrarenal to compare manifestation glomerular ofand AAV tubulointerstitial in association lesions with levelsin of circulatingANCA GN complementanalogous to the components Banff classification C3c and and C4. extrarenal manifestation of AAV in association with levels of circulating complement components C3c and C4. 2. Results 2.1.2. Results Description of Demographic
Load more

Recommended publications
  • WO 2017/048702 Al
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date W O 2017/048702 A l 2 3 March 2017 (23.03.2017) P O P C T (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every C07D 487/04 (2006.01) A61P 35/00 (2006.01) kind of national protection available): AE, AG, AL, AM, A61K 31/519 (2006.01) AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, (21) International Application Number: DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, PCT/US20 16/05 1490 HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, (22) International Filing Date: KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, 13 September 2016 (13.09.201 6) MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, (25) Filing Language: English SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, (26) Publication Language: English TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (30) Priority Data: 62/218,493 14 September 2015 (14.09.2015) US (84) Designated States (unless otherwise indicated, for every 62/218,486 14 September 2015 (14.09.2015) US kind of regional protection available): ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, (71) Applicant: INFINITY PHARMACEUTICALS, INC.
    [Show full text]
  • Pulmonary Microscopic Polyangiitis Presenting As Acute Respiratory Failure from Diffuse Alveolar Hemorrhage
    Case report SARCOIDOSIS VASCULITIS AND DIFFUSE LUNG DISEASES 2015; 32; 372-377 © Mattioli 1885 Pulmonary microscopic polyangiitis presenting as acute respiratory failure from diffuse alveolar hemorrhage Katharine K. Roberts1, Michael M. Chamberlin2, Allen R. Holmes3, Jonathan L. Henderson4, Robert L. Hutton3, William N. Hannah1, Michael J. Morris4 1 Internal Medicine Residency, Department of Medicine, San Antonio Military Medical Center; 2 Internal Medicine, United States Army Health Clinic, Vilseck, Germany; 3 Pathology Residency, Department of Pathology, San Antonio Military Medical Center; 4 Pulmonary/ Critical Care Service, Department of Medicine, San Antonio Military Medical Center Abstract. MicrMicroscopicoscopic polyangiitis and granulomatosis with polyangiitis are rare anti-neutrophilic cytoplas-cytoplas- mic antibody-associated systemic vasculitides that predominantly affect small to medium sized vessels of the lungs and kidneys. These syndromes are largely confined to older adults and often present sub-acutely follow- ing weeks to months of nonspecific prodromal symptoms. While both diseases often manifest within multiple organ systems concurrently, the disease spectrum of microscopic polyangiitis almost always includes the kidneys, while granulomatosis with polyangiitis is most commonly associated with pulmonary disease. We present two cases of rapid onset respiratory failure secondary to diffuse alveolar hemorrhage in young active duty military personnel. After serological testing and surgical lung biopsy, both patients were
    [Show full text]
  • Clinicopathologic Characteristics of Iga Nephropathy with Steroid-Responsive Nephrotic Syndrome
    J Korean Med Sci 2009; 24 (Suppl 1): S44-9 Copyright � The Korean Academy ISSN 1011-8934 of Medical Sciences DOI: 10.3346/jkms.2009.24.S1.S44 Clinicopathologic Characteristics of IgA Nephropathy with Steroid-responsive Nephrotic Syndrome Nephrotic syndrome is an unusual manifestation of IgA Nephropathy (IgAN). Some Sun Moon Kim, Kyung Chul Moon*, cases respond to steroid treatment. Here we describe a case-series of IgAN patients Kook-Hwan Oh, Kwon Wook Joo, with steroid-responsive nephrotic syndrome. Twelve patients with IgAN with steroid- Yon Su Kim, Curie Ahn, responsive nephrotic syndrome were evaluated and followed up. All patients pre- Jin Suk Han, and Suhnggwon Kim sented with generalized edema. Renal insufficiency was found in two patients. The Departments of Internal Medicine, and Pathology*, renal biopsy of eight patients revealed wide foot process effacement in addition to Seoul National University College of Medicine, Seoul, the typical features of IgAN. They showed complete remission after steroid thera- Korea py. Seven relapses were reported in five patients; six of the relapsed cases respond- ed to steroid therapy. Compared with steroid-non-responsive patients, the patients with steroid-responsive nephrotic syndrome had shorter symptom duration, more Received : 1 September 2008 weight gain, more proteinuria, and lower histologic grade than did those that had Accepted : 10 December 2008 steroid-non-responsive nephrotic syndrome at presentation. None of the respon- ders progressed to end stage renal disease, whereas five (38%) non-responders required dialysis or renal transplantation. Patients with IgAN who have steroid-respon- Address for correspondence sive nephrotic syndrome likely have both minimal change disease and IgAN.
    [Show full text]
  • ANCA--Associated Small-Vessel Vasculitis
    ANCA–Associated Small-Vessel Vasculitis ISHAK A. MANSI, M.D., PH.D., ADRIANA OPRAN, M.D., and FRED ROSNER, M.D. Mount Sinai Services at Queens Hospital Center, Jamaica, New York and the Mount Sinai School of Medicine, New York, New York Antineutrophil cytoplasmic antibodies (ANCA)–associated vasculitis is the most common primary sys- temic small-vessel vasculitis to occur in adults. Although the etiology is not always known, the inci- dence of vasculitis is increasing, and the diagnosis and management of patients may be challenging because of its relative infrequency, changing nomenclature, and variability of clinical expression. Advances in clinical management have been achieved during the past few years, and many ongoing studies are pending. Vasculitis may affect the large, medium, or small blood vessels. Small-vessel vas- culitis may be further classified as ANCA-associated or non-ANCA–associated vasculitis. ANCA–asso- ciated small-vessel vasculitis includes microscopic polyangiitis, Wegener’s granulomatosis, Churg- Strauss syndrome, and drug-induced vasculitis. Better definition criteria and advancement in the technologies make these diagnoses increasingly common. Features that may aid in defining the spe- cific type of vasculitic disorder include the type of organ involvement, presence and type of ANCA (myeloperoxidase–ANCA or proteinase 3–ANCA), presence of serum cryoglobulins, and the presence of evidence for granulomatous inflammation. Family physicians should be familiar with this group of vasculitic disorders to reach a prompt diagnosis and initiate treatment to prevent end-organ dam- age. Treatment usually includes corticosteroid and immunosuppressive therapy. (Am Fam Physician 2002;65:1615-20. Copyright© 2002 American Academy of Family Physicians.) asculitis is a process caused These antibodies can be detected with indi- by inflammation of blood rect immunofluorescence microscopy.
    [Show full text]
  • The Case for Lupus Nephritis
    Journal of Clinical Medicine Review Expanding the Role of Complement Therapies: The Case for Lupus Nephritis Nicholas L. Li * , Daniel J. Birmingham and Brad H. Rovin Department of Internal Medicine, Division of Nephrology, The Ohio State University, Columbus, OH 43210, USA; [email protected] (D.J.B.); [email protected] (B.H.R.) * Correspondence: [email protected]; Tel.: +1-614-293-4997; Fax: +1-614-293-3073 Abstract: The complement system is an innate immune surveillance network that provides defense against microorganisms and clearance of immune complexes and cellular debris and bridges innate and adaptive immunity. In the context of autoimmune disease, activation and dysregulation of complement can lead to uncontrolled inflammation and organ damage, especially to the kidney. Systemic lupus erythematosus (SLE) is characterized by loss of tolerance, autoantibody production, and immune complex deposition in tissues including the kidney, with inflammatory consequences. Effective clearance of immune complexes and cellular waste by early complement components protects against the development of lupus nephritis, while uncontrolled activation of complement, especially the alternative pathway, promotes kidney damage in SLE. Therefore, complement plays a dual role in the pathogenesis of lupus nephritis. Improved understanding of the contribution of the various complement pathways to the development of kidney disease in SLE has created an opportunity to target the complement system with novel therapies to improve outcomes in lupus nephritis. In this review, we explore the interactions between complement and the kidney in SLE and their implications for the treatment of lupus nephritis. Keywords: lupus nephritis; complement; systemic lupus erythematosus; glomerulonephritis Citation: Li, N.L.; Birmingham, D.J.; Rovin, B.H.
    [Show full text]
  • Vasculitis: Pearls for Early Diagnosis and Treatment of Giant Cell Arteritis
    Vasculitis: Pearls for early diagnosis and treatment of Giant Cell Arteritis Mary Beth Humphrey, MD, PhD Professor of Medicine McEldowney Chair of Immunology [email protected] Office Phone: 405 271-8001 ext 35290 October 2019 Relevant Disclosure and Resolution Under Accreditation Council for Continuing Medical Education guidelines disclosure must be made regarding relevant financial relationships with commercial interests within the last 12 months. Mary Beth Humphrey I have no relevant financial relationships or affiliations with commercial interests to disclose. Experimental or Off-Label Drug/Therapy/Device Disclosure I will be discussing experimental or off-label drugs, therapies and/or devices that have not been approved by the FDA. Objectives • To recognize early signs of vasculitis. • To discuss Tocilizumab (IL-6 inhibitor) as a new treatment option for temporal arteritis. • To recognize complications of vasculitis and therapies. Professional Practice Gap Gap 1: Application of imaging recommendations in large vessel vasculitis Gap 2: Application of tocilizimab in treatment of giant cell vasculitis Cranial Symptoms Aortic Vision loss Aneurysm GCA Arm PMR Claudication FUO Which is not a risk factor or temporal arteritis? A. Smoking B. Female sex C. Diabetes D. Northern European ancestry E. Age Which is not a risk factor or temporal arteritis? A. Smoking B. Female sex C. Diabetes D. Northern European ancestry E. Age Giant Cell Arteritis • Most common form of systemic vasculitis in adults – Incidence: ~ 1/5,000 persons > 50 yrs/year – Lifetime risk: 1.0% (F) 0.5% (M) • Cause: unknown At risk: Women (80%) > men (20%) Northern European ancestry>>>AA>Hispanics Age: average age at onset ~73 years Smoking: 6x increased risk Kermani TA, et al Ann Rheum Dis.
    [Show full text]
  • Extrarenal Complications of the Nephrotic Syndrome
    Kidney International, Vol. 33 (/988), pp. 1184—1202 NEPHROLOGY FORUM Extrarenal complications of the nephrotic syndrome Principal discussant: DAVID B. BERNARD The University Hospital and Boston University Sc/zoo!ofMedicine, Boston, Massachusetts present and equal. The temperature was 100°F. The blood pressure was 110/70 mm Hg in the right arm with the patient supine and standing. The Editors patient had no skin rashes, peteehiae, clubbing, or jaundice. Examina- JORDANJ. COHEN tion of the head and neck revealed intact cranial nerves and normal fundi. Ears, nose, and throat were normal. The jugular venous pressure Jot-IN T. HARRtNOTON was not increased. No lymph glands were palpable in the neck or JEROME P. KASSIRER axillae, and the trachea was midline, cardiac examination was normal. NICOLA05 E. MAmAs Examination of the lungs revealed coarse rales at the right base but no other abnormalities. Abdominal examination revealed aseites, but no Editor abdominal guarding, tenderness, or rigidity. The liver and spleen were Managing not palpable and no masses were present. The urine contained 4± CHERYL J. ZUSMAN protein; microscopic examination revealed free fat droplets, many oval fat bodies, and numerous fatty casts. Five to 10 red blood cells were seen per high-power field, but no red blood cell casts were present. A Universityof'Chicago Pritzker School of Medicine 24-hr urine collection contained 8 g of protein. The BUN was 22 mg/dl; creatinine, 2.0 mg/dl; and electrolytes were and normal. Serum total calcium was 7.8 mg/dl, and the phosphorus was 4.0 Taf is University School of' Medicine mg/dl.
    [Show full text]
  • Glomerulonephritis Management in General Practice
    Renal disease • THEME Glomerulonephritis Management in general practice Nicole M Isbel MBBS, FRACP, is Consultant Nephrologist, Princess Alexandra lomerular disease remains an important cause Hospital, Brisbane, BACKGROUND Glomerulonephritis (GN) is an G and Senior Lecturer in important cause of both acute and chronic kidney of renal impairment (and is the commonest cause Medicine, University disease, however the diagnosis can be difficult of end stage kidney disease [ESKD] in Australia).1 of Queensland. nikky_ due to the variability of presenting features. Early diagnosis is essential as intervention can make [email protected] a significant impact on improving patient outcomes. OBJECTIVE This article aims to develop However, presentation can be variable – from indolent a structured approach to the investigation of patients with markers of kidney disease, and and asymptomatic to explosive with rapid loss of kidney promote the recognition of patients who need function. Pathology may be localised to the kidney or further assessment. Consideration is given to the part of a systemic illness. Therefore diagnosis involves importance of general measures required in the a systematic approach using a combination of clinical care of patients with GN. features, directed laboratory and radiological testing, DISCUSSION Glomerulonephritis is not an and in many (but not all) cases, a kidney biopsy to everyday presentation, however recognition establish the histological diagnosis. Management of and appropriate management is important to glomerulonephritis (GN) involves specific therapies prevent loss of kidney function. Disease specific directed at the underlying, often immunological cause treatment of GN may require specialist care, of the disease and more general strategies aimed at however much of the management involves delaying progression of kidney impairment.
    [Show full text]
  • Audio Vestibular Gluco Corticoid General and Local Or Cytotoxic Agents
    Global Journal of Otolaryngology ISSN 2474-7556 Case Report Glob J Otolaryngol Volume 13 Issue 5 - March 2018 Copyright © All rights are reserved by Cristina Otilia Laza DOI: 10.19080/GJO.2018.13.555871 Autoimmune Granulomatosis with Polyangiitis or Wegener Granulomatosis Cristina Otilia Laza1*, Gina Enciu2, Luminita Micu2 and Maria Suta3 1Department of ENT, County Clinical Emergency Hospital of Constanta, Romania 2Department of Anatomo pathology, County Clinical Emergency Hospital of Constanta, Romania 3Department of Rheumatology, County Clinical Emergency Hospital of Constanta, Romania Submission: February 19, 2018; Published: March 14, 2018 *Corresponding author: Cristina Otilia Laza, Department of ENT, County Clinical Emergency Hospital of Constanta, Romania, Email: Abstract Granulomatosis with polyangiitis, formerly known as Wegener granulomatosis, is a disease that typically consists of a triad of airway necrotizing granulomas, systemic vasculitis, and focal glomerulonephritis. If the disease does not involve the kidneys, it is called limited granulomatosis with polyangiitis. The etiology and pathogenesis of WG are unknown. Infectious, genetic, and environmental risk factors and combinations thereof have been proposed. The evidence to date suggests that WG is a complex, immune-mediated disorder in which tissue production of ANCA, directed against antigens present within the primary granules of neutrophils and monocytes; these antibodies produce tissueinjury damageresults from by interacting the interplay with of primedan initiating neutrophils inflammatory and endothelial event and cells a highly The purposespecific immune of this article response. is to Part present of this 4 patients response all consists diagnosed of the in our department ,with head and neck lesions ,every case with his manifestation and response to the treatment .We consider that a well trained ENT specialist must be able to diagnose and recognize such a disease but this requires knowledge and hard work.
    [Show full text]
  • (Mabthera) Maintenance Therapy for Granulomatosis with Polyangiitis (GPA) and Microscopic Polyangiitis (MPA) NIHRIO (HSRIC) ID: 12979 NICE ID: 9284
    NIHR Innovation Observatory Evidence Briefing: August 2017 Rituximab (MabThera) maintenance therapy for granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) NIHRIO (HSRIC) ID: 12979 NICE ID: 9284 LAY SUMMARY Anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis is a rare condition in which abnormal antibodies attack the body’s own cells, causing inflammation. Granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) are two different types of ANCA-associated vasculitis. These conditions can cause serious organ damage and severely impact quality of life. Following initial treatment, these conditions frequently return. Rituximab is a medicine, delivered as an infusion into the vein. It destroys B cells, the part of the immune system thought to be involved in this type of vasculitis. It is already licensed for use (and recommended by NICE) as a treatment for people with GPA or MPA. There has however not been sufficient evidence to consider the continued use of rituximab as maintenance therapy, although this is already commissioned by NHS England in some instances. The current clinical trial examines the use of rituximab as a maintenance treatment in patients with GPA or MPA. If licensed, rituximab would offer another option for maintenance therapy in this patient cohort. This briefing is based on information available at the time of research and a limited literature search. It is not intended to be a definitive statement on the safety, efficacy or effectiveness of the health technology covered and should not be used for commercial purposes or commissioning without additional information. This briefing presents independent research funded by the National Institute for Health Research (NIHR).
    [Show full text]
  • A New Vision of Iga Nephropathy: the Missing Link
    International Journal of Molecular Sciences Review A New Vision of IgA Nephropathy: The Missing Link Fabio Sallustio 1,2,* , Claudia Curci 2,3,* , Vincenzo Di Leo 3 , Anna Gallone 2, Francesco Pesce 3 and Loreto Gesualdo 3 1 Interdisciplinary Department of Medicine (DIM), University of Bari “Aldo Moro”, 70124 Bari, Italy 2 Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari “Aldo Moro”, 70124 Bari, Italy; [email protected] 3 Nephrology, Dialysis and Transplantation Unit, DETO, University “Aldo Moro”, 70124 Bari, Italy; [email protected] (V.D.L.); [email protected] (F.P.); [email protected] (L.G.) * Correspondence: [email protected] (F.S.); [email protected] (C.C.) Received: 7 December 2019; Accepted: 24 December 2019; Published: 26 December 2019 Abstract: IgA Nephropathy (IgAN) is a primary glomerulonephritis problem worldwide that develops mainly in the 2nd and 3rd decade of life and reaches end-stage kidney disease after 20 years from the biopsy-proven diagnosis, implying a great socio-economic burden. IgAN may occur in a sporadic or familial form. Studies on familial IgAN have shown that 66% of asymptomatic relatives carry immunological defects such as high IgA serum levels, abnormal spontaneous in vitro production of IgA from peripheral blood mononuclear cells (PBMCs), high serum levels of aberrantly glycosylated IgA1, and an altered PBMC cytokine production profile. Recent findings led us to focus our attention on a new perspective to study the pathogenesis of this disease, and new studies showed the involvement of factors driven by environment, lifestyle or diet that could affect the disease.
    [Show full text]
  • Understanding the Cryoglobulinemias
    Current Rheumatology Reports (2019) 21:60 https://doi.org/10.1007/s11926-019-0859-0 VASCULITIS (L ESPINOZA, SECTION EDITOR) Understanding the Cryoglobulinemias Alejandro Fuentes1 & Claudia Mardones1 & Paula I. Burgos1 # Springer Science+Business Media, LLC, part of Springer Nature 2019 Abstract Purpose of the Review Cryoglobulins are immunoglobulins with the ability to precipitate at temperatures <37 °C. They are related to hematological disorders, infections [especially hepatitis C virus (HCV)], and autoimmune diseases. In this article, the state of the art on Cryoglobulinemic Vasculitis (CV), in a helpful and schematic way, with a special focus on HCV related Mixed Cryoglobulinemia treatment are reviewed. Recent Findings Direct – acting antivirals (DAA) against HCV have emerged as an important key in HCV treatment to related Cryoglobulinemic Vasculitis, and should be kept in mind as the initial treatment in non–severe manifestations. On the other hand, a recent consensus panel has published their recommendations for treatment in severe and life threatening manifestations of Mixed Cryoglobulinemias. Summary HCV-Cryoglobulinemic vasculitis is the most frequent form of CV. There are new treatment options in HCV-CV with DAA, with an important number of patients achieving complete response and sustained virologic response (SVR). In cases of severe forms of CV, treatment with Rituximab and PLEX are options. The lack of data on maintenance therapy could impulse future studies in this setting. Keywords HCV . Mixed Cryoglobulinemia . Type I Cryoglobulinemia . gC1qR . Direct-acting antivirals . Rituximab Introduction and Definitions tion of the total pool of cryoprecipitable immunocomplexes in targeted vessels and due to false negative results owing to im- Cryoglobulins are immunoglobulins (Ig) that precipitate in vitro proper blood sampling or inadequate laboratory processes [4].
    [Show full text]