title: Antineutrophil cytoplasmic antibody positivity in IgG4-related disease: A case report and review of the literature.
abstract: BACKGROUND
  IgG4-related disease (IgG4-RD) is a fibroinflammatory condition characterized by serum IgG4 elevation and tissue infiltration of IgG4-positive plasma cells. Substantial overlap between IgG4-RD and antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitides (AAV) exists in terms of organ involvement and histopathological features. A positive ANCA assay is regarded as a highly specific finding in favor of an AAV, and generally influences away from a diagnosis of IgG4-RD. Recent reports, however, have raised the possibility that some patients with IgG4-RD are ANCA positive, thus suggesting reconsideration of the role of ANCA in the diagnostic workup. In the present work, we describe the first case of concomitant biopsy-proven IgG4-RD and granulomatosis with polyangiitis (GPA), demonstrating antiproteinase 3 (PR3) ANCA of the IgG4 subclass in the patient's serum. We also review the literature in order to provide clinicians with tools for interpreting ANCA positivity in IgG4-RD patients.
  
  
  METHODS
  A 51-year-old woman was referred for left exopthalmos due to lacrimal gland enlargement and increased serum IgG4 concentration. IgG4-RD was suspected and further imaging studies disclosed multiple pulmonary masses in the right lung. Histological analysis of the left lacrimal gland was diagnostic for IgG4-RD, but lung biopsy showed typical features of GPA. ANCA assay was positive for anti-PR3 antibodies. Further immunofluorescence studies demonstrated anti-PR3 antibodies of IgG1 and IgG4 subclass. Treatment with rituximab induced swift remission of both IgG4-RD and GPA manifestations. We identified 9 other reports of patients with IgG4-RD and positive ANCA in the English literature, 5 cases with biopsy-proven IgG4-RD and 4 cases in whom IgG4-RD was diagnosed presumptively. Four patients had also histological evidence of concomitant AAV.
  
  
  CONCLUSIONS
  The present work demonstrates that ANCA positivity in patients with biopsy-proven IgG4-RD should prompt the exclusion of a concomitant vasculitic process; a positive ANCA does not exclude the diagnosis of IgG4-RD; confirmation through immunoenzymatic assays of the ANCA specificity, clinical-pathological correlation, and histopathological evaluation remain crucial steps for the differential diagnosis between AAV and IgG4-RD.
authors: Università Vita-Salute San Raffaele, IRCCS-San Raffaele Scientific Institute Division of Immunology, Transplantation and Infectious Diseases, IRCCS-San Raffaele Scientific Institute Unit of Medicine and Clinical Immunology, IRCCS-San Raffaele Scientific Institute Department of Thoracic Surgery, IRCCS-San Raffaele Scientific Institute Laboraf Diagnostic Research, IRCCS-San Raffaele Scientific Institute Division of Nuclear Medicine, IRCCS-San Raffaele Scientific Institute Department of Ophthalmology, IRCCS-San Raffaele Scientific Institute, Milan, Italy Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA Pathology Unit, IRCCS-San Raffaele Scientific Institute, Milan, Italy.
authors: Emanuel
authors: E
authors: Della-Torre
authors: Marco
authors: M
authors: Lanzillotta
authors: Corrado
authors: C
authors: Campochiaro
authors: Emanuele
authors: E
authors: Bozzalla
authors: Enrica
authors: E
authors: Bozzolo
authors: Alessandro
authors: A
authors: Bandiera
authors: Elena
authors: E
authors: Bazzigaluppi
authors: Carla
authors: C
authors: Canevari
authors: Giulio
authors: G
authors: Modorati
authors: John H
authors: JH
authors: Stone
authors: Angelo
authors: A
authors: Manfredi
authors: Claudio
authors: C
authors: Doglioni
mesh_terms: D019268:Antibodies, Antineutrophil Cytoplasmic / Q000097:blood* / Q000276:immunology; D001706:Biopsy; D003937:Diagnosis, Differential; D005260:Female; D014890:Granulomatosis with Polyangiitis / Q000097:blood / Q000150:complications / Q000175:diagnosis* / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D008875:Middle Aged; D015423:Scleritis / Q000209:etiology
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D007074:Immunoglobulin G