• 1.

    Rump JAScholmerich JGross V, et al. A new type of perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA) in active ulcerative colitis but not in Crohn's disease. Immunobiology 1990; 181:406413.

    • Search Google Scholar
    • Export Citation
  • 2.

    Radice ASinico RA. Antineutrophilic cytoplasmic antibodies (ANCA). Autoimmunity 2005; 38:93103.

  • 3.

    Hagen ECDaha MRHermans J, et al. Diagnostic value of standardized assays for anti-neutrophil cytoplasmic antibodies in idiopathic systemic vasculitis. EC/BCR Project for ANCA Assay Standardization. Kidney Int 1998; 53:743753.

    • Search Google Scholar
    • Export Citation
  • 4.

    Choi HKLiu SMerkel PA, et al. Diagnostic performance of antineutrophil cytoplasmic antibody tests for idiopathic vasculitides: metaanalysis with a focus on antimyeloperoxidase antibodies. J Rheumatol 2001; 28:15841590.

    • Search Google Scholar
    • Export Citation
  • 5.

    Gross WL. Aniteutrophil cytoplasmic autoantibody testing in vasculitides. Rheum Dis Clin North Am 1995; 21:9871011.

  • 6.

    Falk RJHogan SCarey TS, et al. Clinical course of anti-neutrophil cytoplasmic autoantibody–associated glomerulonephritis and systemic vasculitis. Ann Intern Med 1990; 113:656663.

    • Search Google Scholar
    • Export Citation
  • 7.

    Homsak EMicetic-Turk DBozic B. Autoantibodies pANCA, GAB and PAB in inflammatory bowel disease: prevalence, characteristics and diagnostic value. Wien Klin Wochenschr 2010; 122(suppl 2):1925.

    • Search Google Scholar
    • Export Citation
  • 8.

    Anand VRussell ASTsuyuki R, et al. Perinuclear antineutrophil cytoplasmic autoantibodies and anti–Saccharomyces cerevisiae antibodies as serological markers are not specific in the identification of Crohn's disease and ulcerative colitis. Can J Gastroenterol 2008; 22:3336.

    • Search Google Scholar
    • Export Citation
  • 9.

    Allenspach KLomas BWieland B, et al. Evaluation of perinuclear anti-neutrophilic cytoplasmic autoantibodies as an early marker of protein-losing enteropathy and protein-losing nephropathy in Soft Coated Wheaten Terriers. Am J Vet Res 2008; 69:13011304.

    • Search Google Scholar
    • Export Citation
  • 10.

    Jaskowski TDLitwin CAHill HR. Analysis of serum antibodies in patients suspected of having inflammatory bowel disease. Clin Vaccine Immunol 2006; 13:655660.

    • Search Google Scholar
    • Export Citation
  • 11.

    Luckschander NAllenspach KHall J, et al. Perinuclear anti-neutrophilic cytoplasmic antibody and response to treatment in diarrheic dogs with food responsive disease or inflammatory bowel disease. J Vet Intern Med 2006; 20:221227.

    • Search Google Scholar
    • Export Citation
  • 12.

    Mokrowiecka AGasiorowska AMalecka-Panas E. pANCA and ASCA in the diagnosis of different subtypes of inflammatory bowel disease. Hepatogastroenterology 2007; 54:14431448.

    • Search Google Scholar
    • Export Citation
  • 13.

    Allenspach KLuckschander NStyner M, et al. Evaluation of assays for perinuclear antineutrophilic cytoplasmic antibodies and antibodies to Saccharomyces cerevisiae in dogs with inflammatory bowel disease. Am J Vet Res 2004; 65:12791283.

    • Search Google Scholar
    • Export Citation
  • 14.

    Mancho CRodriguez-Franco FGarcia-Sancho M, et al. Detection of anti-neutrophil cytoplasmic antibodies (ANCA) in serum from dogs with inflammatory bowel disease. Clin Vet Pequenos Anim 2007; 27:121126.

    • Search Google Scholar
    • Export Citation
  • 15.

    Nakamura RMBarry M. Serologic markers in inflammatory bowel disease (IBD). MLO Med Lab Obs 2001; 33:819.

  • 16.

    Hirai YIyoda MShibata T, et al. Lupus nephritis associated with positive MPO-ANCA in a patient with underlying autoimmune hemolytic anemia. Clin Exp Nephrol 2008; 12:393397.

    • Search Google Scholar
    • Export Citation
  • 17.

    Ohhashi JMiyamoto MIshikawa S, et al. Crescentic glomerulonephritis with positive antineutrophil cytoplasmic autoantibody specific for myeloperoxidase associated with autoimmune hemolytic anemia and thrombocytopenic purpura. Intern Med 2000; 39:650654.

    • Search Google Scholar
    • Export Citation
  • 18.

    Hirokawa M. Paraneoplastic autoimmune disorders. Gan To Kagaku Ryoho 2010; 37:980983.

  • 19.

    Faruqi SKastelik JAMcGivem DV. Diagnostic pitfall: Mycobacterium avium complex pulmonary infection and positive ANCA. Eur J Intern Med 2008; 19:216218.

    • Search Google Scholar
    • Export Citation
  • 20.

    Teixeira LMahr AJaureguy F, et al. Low seroprevalence and poor specificity of antineutrophil cytoplasmic antibodies in tuberculosis. Rheumatology 2005; 44:247250.

    • Search Google Scholar
    • Export Citation
  • 21.

    Flores-Suarez LFCabiedes JVilla AR, et al. Prevalence of anti-neutrophil cytoplasmic autoantibodies in patients with tuberculosis. Rheumatology 2003; 42:223229.

    • Search Google Scholar
    • Export Citation
  • 22.

    Holmes AHGreenough TCBalady GJ, et al. Bartonella henselae endocarditis in an immunecompetent adult. Clin Infect Dis 1995; 21:10041007.

    • Search Google Scholar
    • Export Citation
  • 23.

    Brahn EPegues DAYao QP, et al. Mucocutaneous leishmaniasis masquerading as Wegener granulomatosis. J Clin Rheumatol 2010; 16:125128.

    • Search Google Scholar
    • Export Citation
  • 24.

    Sugiyama HSahara MImai Y, et al. Infective endocarditis by Bartonella quintana masquerading as antineutrophil cytoplasmic antibody-associated small vessel vasculitis. Cardiology 2009; 114:208211.

    • Search Google Scholar
    • Export Citation
  • 25.

    Smith BETompkins MBBreitschwerdt EB. Antinuclear antibodies can be detected in dog sera reactive to Bartonella vinsonii subsp berkhoffii, Ehrlichia canis, or Leishmania infantum antigens. J Vet Intern Med 2004; 18:4751.

    • Search Google Scholar
    • Export Citation
  • 26.

    Ciaramella POliva GDeLuna R, et al. A retrospective clinical study of canine leishmaniasis in 150 dogs naturally infected by Leishmania infantum. Vet Rec 1997; 141:539543.

    • Search Google Scholar
    • Export Citation
  • 27.

    Henn JBLiu CHKasten RW, et al. Seroprevalence of antibodies against Bartonella species and evaluation of risk factors and clinical signs associated with seropositivity in dogs. Am J Vet Res 2005; 66:688694.

    • Search Google Scholar
    • Export Citation
  • 28.

    Overmann JASharkey LCWeiss DJ, et al. Performance of 2 microtiter canine Coombs' tests. Vet Clin Pathol 2007; 36:179183.

  • 29.

    Solano-Gallego LLlull JOsso M, et al. A serological study of exposure to arthropod-borne pathogens in dogs from northeastern Spain. Vet Res 2006; 37:231244.

    • Search Google Scholar
    • Export Citation
  • 30.

    Gerber BHaug KEichenberger S, et al. Comparison of a rapid immunoassay for antibodies to the C6 antigen with conventional tests for antibodies to Borrelia burgdorferi in dogs in Europe. Vet Rec 2009; 165:594597.

    • Search Google Scholar
    • Export Citation
  • 31.

    Riera CValladares JEGallego M, et al. Serological and parasitological follow-up in dogs experimentally infected with Leishmania infantum and treated with meglumine antimoniate. Vet Parasitol 1999; 84:3347.

    • Search Google Scholar
    • Export Citation
  • 32.

    Katrib ASturgess ABertouch JV. Systemic sclerosis and antineutrophil cytoplasmic autoantibady-associated renal failure. Rheumatol Int 1999; 19:6163.

    • Search Google Scholar
    • Export Citation
  • 33.

    Spornk PEBootsma HHorst G, et al. Antineutrophil cytoplasmic antibodies in systemic lupus erythematosus. Rheumatology 1996; 35:625631.

    • Search Google Scholar
    • Export Citation
  • 34.

    Hochman JA. Autoimmune hemolytic anemia associated with Crohn's disease. Inflamm Bowel Dis 2002; 8:98100.

  • 35.

    Carr APPanciera DLKidd L. Prognostic factors for mortality and thromboembolism in canine immune-mediated hemolytic anemia: a retrospective study of 72 dogs. J Vet Intern Med 2002; 16:504509.

    • Search Google Scholar
    • Export Citation
  • 36.

    Breitschwerdt EBBlann KRStebbins ME, et al. Clinicopathological abnormalities and treatment response in 24 dogs seroreactive to Bartonella vinsonii (berkhoffii) antigens. J Am Anim Hosp Assoc 2004; 40:92101.

    • Search Google Scholar
    • Export Citation
  • 37.

    Goodman RABreitschwerdt EB. Clinicopathologic findings in dogs seroreactive to Bartonella henselae antigens. Am J Vet Res 2005; 66:20602064.

    • Search Google Scholar
    • Export Citation
  • 38.

    Gionchetti PVecchi MRizzello F, et al. Lack of effect of anti-neutrophil cytoplasmic antibodies associated with ulcerative colitis on superoxide anion production from neutrophils. Gut 1997; 40:102104.

    • Search Google Scholar
    • Export Citation
  • 39.

    Schultz HSchinke SMosier K, et al. BPI-ANCA of pediatric cystic fibrosis patients can impair BPI-mediated killing of E. coli DH5 alpha in vitro. Pediatr Pulmonol 2004; 37:158164.

    • Search Google Scholar
    • Export Citation
  • 40.

    Schinke SFellermann KHerlyn K, et al. Autoantibodies against the bactericidal/permeability-increasing protein from inflammatory bowel disease patients can impair the antibiotic activity of bactericidal/permeability-increasing protein. Inflamm Bowel Dis 2004; 10:763770.

    • Search Google Scholar
    • Export Citation
  • 41.

    Cohavy OBruckner DGordon LK, et al. Colonic bacteria express an ulcerative colitis pANCA-related protein epitope. Infect Immun 2000; 68:15421548.

    • Search Google Scholar
    • Export Citation
  • 42.

    Zhao MHJones SJLockwood CM. Bacterial permeability-increasing protein (PBI) is an important antigen of antineutrophil cytoplasmic autoantibodies (ANCA) in vasculitis. Clin Exp Immunol 1995; 99:4956.

    • Search Google Scholar
    • Export Citation
  • 43.

    Vonandrian UHChambers JDMcEvoy LM, et al. 2-step model of leukocyte endothelial-cell interaction in inflammation-distinct roles for lECAM-1 and the leukocyte beta 2 intergrins in vivo. Proc Natl Acad Sci U S A 1991; 88:75387542.

    • Search Google Scholar
    • Export Citation
  • 44.

    Fiebig ELey KArfors KE. Rapid leukocyte accumulation by spontaneous rolling and adhesion in the exteriorised rabbit mesentery. Int J Microcirc Clin Exp 1991; 10:127144.

    • Search Google Scholar
    • Export Citation
  • 45.

    Hickey MJKubes P. Intravascular immunity: the host-pathogen encounter in blood vessels. Nat Rev Immunol 2009; 9:364375.

  • 46.

    McKay DM. Bacterial superantigens: provocateurs of gut dysfunction and inflammation? Trends Immunol 2001; 22:497501.

  • 47.

    Dalwadi HWei BKronenberg M, et al. The Crohn's disease-associated bacterial protein I2 is a novel enteric T cell superantigen. Immunity 2001; 15:149158.

    • Search Google Scholar
    • Export Citation
  • 48.

    Reumaux DDuthilleul PRoos D. Pathogenesis of diseases associated with antineutrophil cytoplasm autoantibodies. Hum Immunol 2004; 65:112.

    • Search Google Scholar
    • Export Citation
  • 49.

    Utz PJAnderson P. Posttranslational protein modifications, apoptosis, and the bypass of tolerance to autoantigens. Arthritis Rheum 1998; 41:11521160.

    • Search Google Scholar
    • Export Citation
  • 50.

    Bell EKChugh SSCook WJ. A case of infection-associated antiproteinase-3-negative cytoplasmic antineutrophil cytoplasmic antibody pauci-immune focal necrotizing glomerulonephritis. Nephrol Dial Transplant 2010; 25:31193123.

    • Search Google Scholar
    • Export Citation
  • 51.

    Alvar JCanavate CMolina R, et al. Canine leishmaniasis. Adv Parasitol 2004; 57:188.

  • 52.

    Otranto DTestini GDantas-Torres F, et al. Diagnosis of canine vector-borne diseases in young dogs: a longitudinal study. J Clin Microbiol 2010; 48:33163324.

    • Search Google Scholar
    • Export Citation
  • 53.

    Pappalardo BLCorrea MTYork CC, et al. Epidemiologic evaluation of the risk factors associated with exposure and seroreactivity to Bartonella vinsonii in dogs. Am J Vet Res 1997; 58:467471.

    • Search Google Scholar
    • Export Citation
  • 54.

    Henn JBVanhorn BAKasten RW, et al. Short report: antibodies to Bartonella vinsonii subsp berkhoffii in Moroccan dogs. Am J Trop Med Hyg 2006; 74:222223.

    • Search Google Scholar
    • Export Citation
  • 55.

    Breitschwerdt EBAtkins CEBrown TT, et al. Bartonella vinsonii subsp berkhoffi and related members of the alpha subdivision of the Proteobacteria in dogs with cardiac arrhythmias, endocarditis, or myocarditis. J Clin Microbiol 1999; 37:36183626.

    • Search Google Scholar
    • Export Citation
  • 56.

    Riding AMD'Cruz DP. A case of mistaken identity: subacute bacterial endocarditis associated with p-antineutrophil cytoplasmic antibody [published online ahead of print Dec 15, 2010]. BMJ Case Rep doi:10.1136/bcr.09.2010.3299.

    • Search Google Scholar
    • Export Citation
  • 57.

    Frank JRBreitschwerdt EB. A retrospective study of ehrlichiosis in 62 dogs from North Carolina and Virginia. J Vet Intern Med 1999; 13:194201.

    • Search Google Scholar
    • Export Citation
  • 58.

    Waner THarrus SWeiss DJ, et al. Demonstration of serum antiplatelet antibodies in experimental acute canine ehrlichiois. Vet Immunol Immunopathol 1995; 48:177182.

    • Search Google Scholar
    • Export Citation
  • 59.

    Harrus SWaner TWeiss DJ, et al. Kinetics of serum antiplatelet antibodies in experimental acute canine ehrlichiosis. Vet Immunol Immunopathol 1996; 51:1320.

    • Search Google Scholar
    • Export Citation
  • 60.

    Cortese LTerrazzano GPiantedosi D, et al. Prevalence of antiplatelet antibodies in dogs naturally co-infected by Leishmania infantum and Ehrlichia canis. Vet J 2011; 188:118121.

    • Search Google Scholar
    • Export Citation
  • 61.

    Agut ACorzo NMurciano J, et al. Clinical and radiographic study of bone and joint lesions in 26 dogs with leishmaniasis. Vet Rec 2003; 153:648652.

    • Search Google Scholar
    • Export Citation
  • 62.

    Vamvakidis CDKoutinas AFKanakoudis G, et al. Masticatory and skeletal muscle myositis in canine leishmaniasis (Leishmania infantum). Vet Rec 2000; 146:698703.

    • Search Google Scholar
    • Export Citation
  • 63.

    Koutinas AFPolizopoulou ZSSaridomichelakis MN, et al. Clinical considerations on canine visceral leishmaniasis in Greece: a retrospective study of 158 cases (1989–1996). J Am Anim Hosp Assoc 1999; 35:376383.

    • Search Google Scholar
    • Export Citation
  • 64.

    Breitschwerdt EBKordick DLMalarkey DE, et al. Endocarditis in a dog due to infection with a novel Bartonella subspecies. J Clin Microbiol 1995; 33:154160.

    • Search Google Scholar
    • Export Citation

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Perinuclear antineutrophil cytoplasmic autoantibodies in dogs infected with various vector-borne pathogens and in dogs with immune-mediated hemolytic anemia

Anna E. Karagianni DVM, MRes1, Laia Solano-Gallego DVM, PhD2, Edward B. Breitschwerdt DVM3, Frédéric P. Gaschen Dr med vet, Dr habil4, Michael J. Day BVMS, PhD, DSc5, Michele Trotta DVM, PhD6, Barbara Wieland Dr med vet, PhD7, and Karin Allenspach Dr med vet, PhD8
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  • 1 Department of Veterinary Clinical Sciences, Royal Veterinary College, University of London, Hatfield, Hertfordshire, AL9 7TA, England.
  • | 2 Department of Pathology and Infectious Diseases, Royal Veterinary College, University of London, Hatfield, Hertfordshire, AL9 7TA, England.
  • | 3 Center for Comparative Medicine and Translational Research, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606.
  • | 4 Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803.
  • | 5 Division of Veterinary Pathology, Infection and Immunity, School of Veterinary Sciences, University of Bristol, Langford, North Somerset, BS40 5DU, England.
  • | 6 Clinica Veterinaria Privata San Marco Srl Unipersonale—Laboratorio d'Analisi, Veterinarie, San Marco via Sorio 114/c, 35141, Padova, Italy.
  • | 7 Department of Veterinary Clinical Sciences, Royal Veterinary College, University of London, Hatfield, Hertfordshire, AL9 7TA, England.
  • | 8 Department of Veterinary Clinical Sciences, Royal Veterinary College, University of London, Hatfield, Hertfordshire, AL9 7TA, England.

Abstract

Objective—To determine the prevalence of perinuclear antineutrophil cytoplasmic autoantibodies (pANCA) in dogs with confirmed or suspected immune-mediated hemolytic anemia (IMHA) or dogs infected with various vector-borne pathogens, including Rickettsia rickettsii, Bartonella henselae, Bartonella vinsonii subsp berkhoffii, Ehrlichia canis, Borrelia burgdorferi, and Leishmania infantum.

Animals—55 dogs with confirmed or suspected IMHA, 140 dogs seroreactive for vector-borne pathogens, and 62 healthy dogs and dogs seronegative for vector-borne pathogens.

Procedures—Samples were allocated to subgroups on the basis of the health status of the dogs and the degree of seroreactivity against various vector-borne pathogens. Serum samples were tested retrospectively via indirect immunofluorescence assay to determine pANCA status.

Results—26 of 55 (47%) dogs with confirmed or suspected IMHA and 67 of 140 (48%) dogs seroreactive for vector-borne pathogens had positive results when tested for pANCA. Serum samples with the highest antibody concentrations against L infantum antigen had the highest proportion (28/43 [65%]) that were positive for pANCA. One of 20 (5%) dogs seronegative for tick-borne pathogens and 8 of 22 (36%) dogs seronegative for L infantum had positive results for pANCA. One of 20 (5%) healthy dogs had serum antibodies against pANCA.

Conclusions and Clinical Relevance—pANCA were detected in a high percentage of dogs with IMHA and vector-borne infectious diseases. Therefore, pANCA may be a relatively nonspecific marker for dogs with inflammatory bowel disease, although they could represent a biomarker for immune-mediated diseases and infections.

Contributor Notes

Dr. Karagianni's present address is Roslin Institute, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian, EH25 9RG, Scotland.

This manuscript represents a portion of a thesis submitted by the first author to the Department of Veterinary Clinical Sciences, Royal Veterinary College, University of London as partial fulfilment of the requirements for a Master of Research degree.

Address correspondence to Dr. Allenspach (kallenspach@rvc.ac.uk).