Coexistence of anti-GBM antibodies and MPO-ANCA in a patient with systemic vasculitis and crescentic glomerulonephritis
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Fernandes, J.A. Lopes, L. Correia, S. Gonçalves, S. Jorge" "autores" => array:5 [ 0 => array:3 [ "Iniciales" => "P." "apellidos" => "Fernandes" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] ] ] 1 => array:4 [ "Iniciales" => "J.A." "apellidos" => "Lopes" "email" => array:1 [ 0 => "jalopes93@hotmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] ] ] 2 => array:3 [ "Iniciales" => "L." "apellidos" => "Correia" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "affb" ] ] ] 3 => array:3 [ "Iniciales" => "S." "apellidos" => "Gonçalves" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] ] ] 4 => array:3 [ "Iniciales" => "S." "apellidos" => "Jorge" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Nephrology and Renal Transplantation Department, Hospital de Santa Maria, Lisboa, Portugal, " "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "affa" ] 1 => array:3 [ "entidad" => "Anatomical Pathology Department, Hospital de Santa Maria, Lisboa, Portugal, " "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "affb" ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig1" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "10563_108_7732_en_10563_f1.jpg" "Alto" => 257 "Ancho" => 333 "Tamanyo" => 27773 ] ] "descripcion" => array:1 [ "en" => "Kidney biopsy showing crescentic glomerulonephritis (Masson trichrome, x100)." ] ] ] "textoCompleto" => "<p class="elsevierStylePara"><span class="elsevierStyleBold"> </span></p><p class="elsevierStylePara"><span class="elsevierStyleBold">Dear Editor:</span></p><p class="elsevierStylePara"> </p><p class="elsevierStylePara">Anti-glomerular basement membrane (GBM) antibodies are sometimes detected in patients with sera that contain antineutrophil cytoplasmic antibodies (ANCAs), especially in those with specificity for myeloperoxidase (MPO)<span class="elsevierStyleSup">1-5</span>. Double positive patients may have a clinical course and response to treatment more typical of vasculitis than of anti-GBM disease, and renal function recovery may be more likely if ANCAs are present<span class="elsevierStyleSup">1</span>. Recent observations<span class="elsevierStyleSup">3-5</span> however, have failed to detect the differences described in early reports.</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara">Here, we present a case of a 62 years-old Caucasian female with rhinosinusitis and asthma diagnosed 2 years before was admitted at our Department with renal failure requiring dialysis. She had anorexia, weight loss (15% of body weight), and weakness over the last 7 months. One month before the hospitalization she developed fever, persistent cough, dyspnea, myalgias, arthralgias, numbness and <span class="elsevierStyleItalic">weakness of lower limbs</span>. Physical examination revealed pale skin, blood pressure of 135/78 mmHg, heart rate of 68 beats per minute, respiratory rate of 18 cycles per minute, body temperature of 36.3 °C, oliguria (350 ml/day). Cardiac, pulmonary and abdominal examination did not reveal any changes. There was no ocular inflammation, joint tenderness or effusion, and rash. Neither edema nor <span class="elsevierStyleItalic">tenderness</span> of lower limbs, nor peripheral lymphadenopathies was present. Neurologic examination disclosed asymmetrical motor and sensory compromise of lower limbs.</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara">Laboratory disclosed microcytic hypochromic anemia (hemoglobin, 4.8 g/dl; mean globular volume, 76.9 fl; mean globular hemoglobin, 24.1 pg), leucocytosis (14.460/mm<span class="elsevierStyleSup">3</span>), eosinophilia (2.300/mm<span class="elsevierStyleSup">3</span>), thrombocytosis (880.000/mm<span class="elsevierStyleSup">3</span>), elevation of erythrocyte sedimentation rate (142 mm/hour) and of C-reactive protein (20 mg/dl), renal failure (uremia, 199 mg/dl; creatinemia, 6.1 mg/dl), and hiperkalemia (8.2 mEq/l). Urinalysis showed proteinuria of 100 mg/dl and 200 erythrocytes/microliter. Serum protein electrophoresis revealed IgG/K monoclonal gammopathy. Hepatic function tests, lactate dehydrogenase, calcemia, and phosphatemia were on the normal range.</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara">Renal ultrasound revealed normal sized kidneys, cortical hyperechogenicity, normal parenquimatous differentiation, and no hydronephrosis. Computed tomography (CT) of the face disclosed mucous thickening of the frontal, ethmoid, sphenoid and maxillary sinuses lining, and CT of the chest revealed ground-glass opacities widely spread across both lungs. Lower limbs electromiogram revealed severe multiple mononeuritis. Bone marrow biopsy disclosed eosinophilic hypercellularity and no morphologic abnormalities. A renal biopsy was performed and showed CGN with linear deposition of IgG along the glomerular capillaries (Figure 1 and figure 2). Serology for lupus (antinuclear, anti-double strand deoxyribonucleic acid, anti-Smith, extractable nuclear and anti-ribonucleoprotein antibodies) was negative. Serum C3, and C4 were on the normal range. Serology for human immunodeficiency virus types 1 and 2, hepatitis B, hepatitis C was also negative. Indirect immunofluorescence assay detected perinuclear ANCA (p-ANCA) (90 U/ml) and enzyme-linked immunosorbent assay (ELISA) revealed MPO specificity. Anti-GBM antibodies in serum (169 U/ml) were detected by direct ELISA. According to these, the diagnosis of CGN with double-positivity for anti-GBM antibodies and MPO-ANCA was established. She underwent intermittent hemodialysis, and immunosupressive therapy with metilprednisolone (15 mg/kg/day, 3 days, IV) followed by oral prednisone (1 mg/kg/day), cyclophosphamide (750 mg/m<span class="elsevierStyleSup">2</span>, monthly, IV), and plasma exchange with daily exchange of one volume of plasma for 5% human albumin for 14 days was initiated. She also received red blood cell transfusions. Two weeks later, the patient was asymptomatic, recovered diuresis, and improved renal function. At hospital discharge (day 38), uremia and creatinemia were 148 mg/dl and 2.5 mg/dl, respectively, and hemoglobin was 10.9 g/dl. She had no clinical or laboratorial evidence of disease relapse, and she remains out of dialysis.</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara">This case illustrates several interesting points. The patient presented with symptoms and signs in other organs suggesting systemic vasculitis. Serologic tests revealed coexistence of anti-GBM antibodies and MPO-ANCA, and histology showed CGN with linear deposition of IgG along the glomerular capillaries.  Although the patient presented with renal failure requiring dialysis, there was renal function recovery after immunosupression with plasma exchange, without evidence of disease relapse.</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara">In a substantial proportion of patients with CGN double-positivity for anti-GBM antibodies and ANCAs (mostly MPO-ANCA) is detected<span class="elsevierStyleSup">1-5</span>. Double-positive patients may have a clinical course and response to treatment more typical of vasculitis than of anti-GBM disease, and have possibly developed anti-GBM antibodies secondary to vasculitic glomerular damage. Some patients have symptoms and signs in other organs suggesting systemic vasculitis, and renal function recovery may be more likely if ANCAs are present<span class="elsevierStyleSup">1</span>. Recent observations<span class="elsevierStyleSup">3-5</span> however, have failed to detect the differences described earlier. Rutgers et al.<span class="elsevierStyleSup">4</span> reviewed 46 MPO-ANCA-positive, 10 double-positive and 13 anti-GBM-positive patients with CGN. Creatinemia was lower in ANCA-positive patients compared to double-positive or anti-GBM-positive patients (5.0, 10.3, 9.6 mg/dl, respectively; <span class="elsevierStyleItalic">P</span> = 0.01), and renal survival was different among the 3 groups (65%, 10%, and 15% of dialysis at 1 year, respectively; <span class="elsevierStyleItalic">P</span> = 0.04). Levy et al.<span class="elsevierStyleSup">3</span> analyzed 27 patients with CGN and double-positivity for anti-GBM antibodies and ANCAs (mostly MPO-ANCA), and described patient and renal survival rates of 52% and 26%, respectively, at one year. Sixty-eight percent of patients were dialysis-dependent at presentation, and none of these recovered renal function, despite immunosuppression with or without plasma exchange.</p><p class="elsevierStylePara"> </p><p class="elsevierStylePara">Although patients with CGN and double-positivity for anti-GBM antibodies and ANCAs may have a poor prognosis when presenting with severe disease, behaving more like anti-GBM disease than vasculitis, and recovery from severe renal failure may be rare, this case highlights that immunosupressive therapy with plasma exchange can improve patient and renal outcome in such patients.</p><p class="elsevierStylePara"><span class="elsevierStyleBold"> </span></p><p class="elsevierStylePara"><a href="grande/10563_108_7732_en_10563_f1.jpg" class="elsevierStyleCrossRefs"><img src="10563_108_7732_en_10563_f1.jpg" alt="Kidney biopsy showing crescentic glomerulonephritis (Masson trichrome, x100)."></img></a></p><p class="elsevierStylePara">Figure 1. Kidney biopsy showing crescentic glomerulonephritis (Masson trichrome, x100).</p><p class="elsevierStylePara"><a href="grande/10563_108_7733_en_10563_f2.jpg" class="elsevierStyleCrossRefs"><img src="10563_108_7733_en_10563_f2.jpg" alt="Immunofluorescence microscopy showing linear deposition of IgG along the glomerular capillaries (x400)."></img></a></p><p class="elsevierStylePara">Figure 2. Immunofluorescence microscopy showing linear deposition of IgG along the glomerular capillaries (x400).</p>" "tienePdf" => false "multimedia" => array:2 [ 0 => array:8 [ "identificador" => "fig1" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "10563_108_7732_en_10563_f1.jpg" "Alto" => 257 "Ancho" => 333 "Tamanyo" => 27773 ] ] "descripcion" => array:1 [ "en" => "Kidney biopsy showing crescentic glomerulonephritis (Masson trichrome, x100)." ] ] 1 => array:8 [ "identificador" => "fig2" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "copyright" => "Elsevier España" "figura" => array:1 [ 0 => array:4 [ "imagen" => "10563_108_7733_en_10563_f2.jpg" "Alto" => 229 "Ancho" => 333 "Tamanyo" => 18080 ] ] "descripcion" => array:1 [ "en" => "Immunofluorescence microscopy showing linear deposition of IgG along the glomerular capillaries (x400)." ] ] ] "bibliografia" => array:2 [ "titulo" => "Bibliography" "seccion" => array:1 [ 0 => array:1 [ "bibliografiaReferencia" => array:6 [ 0 => array:3 [ "identificador" => "bib1" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "\u{A0}" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 1 => array:3 [ "identificador" => "bib2" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Bolton WK. Goodpasture's syndrome. Kidney Int 1996;50:1753-66. <a href="http://www.ncbi.nlm.nih.gov/pubmed/8914046" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 2 => array:3 [ "identificador" => "bib3" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Jannette JC. Rapidly progressive crescentic glomerulonephritis. Kidney Int 2003;63:1164-77. <a href="http://www.ncbi.nlm.nih.gov/pubmed/12631105" target="_blank">[Pubmed]</a>" "contribucion" => array:1 [ 0 => null ] "host" => array:1 [ 0 => null ] ] ] ] 3 => array:3 [ "identificador" => "bib4" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:3 [ "referenciaCompleta" => "Levy JB, Hammad T, Coulthart A, Dougan T, Pusey CD. Clinical features and outcome of patients with both ANCA and anti-GBM antibodies. 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| 2023 January | 60 | 3 | 63 |
| 2022 December | 39 | 6 | 45 |
| 2022 November | 78 | 6 | 84 |
| 2022 October | 45 | 4 | 49 |
| 2022 September | 57 | 3 | 60 |
| 2022 August | 63 | 4 | 67 |
| 2022 July | 46 | 0 | 46 |
| 2022 June | 61 | 5 | 66 |
| 2022 May | 65 | 11 | 76 |
| 2022 April | 75 | 15 | 90 |
| 2022 March | 91 | 11 | 102 |
| 2022 February | 83 | 10 | 93 |
| 2022 January | 79 | 4 | 83 |
| 2021 December | 101 | 5 | 106 |
| 2021 November | 99 | 4 | 103 |
| 2021 October | 122 | 4 | 126 |
| 2021 September | 73 | 8 | 81 |
| 2021 August | 90 | 2 | 92 |
| 2021 July | 70 | 4 | 74 |
| 2021 June | 36 | 7 | 43 |
| 2021 May | 48 | 0 | 48 |
| 2021 April | 122 | 10 | 132 |
| 2021 March | 71 | 11 | 82 |
| 2021 February | 83 | 9 | 92 |
| 2021 January | 52 | 12 | 64 |
| 2020 December | 31 | 5 | 36 |
| 2020 November | 35 | 4 | 39 |
| 2020 October | 55 | 5 | 60 |
| 2020 September | 31 | 3 | 34 |
| 2020 August | 38 | 5 | 43 |
| 2020 July | 45 | 5 | 50 |
| 2020 June | 41 | 17 | 58 |
| 2020 May | 49 | 6 | 55 |
| 2020 April | 44 | 14 | 58 |
| 2020 March | 39 | 13 | 52 |
| 2020 February | 33 | 11 | 44 |
| 2020 January | 58 | 9 | 67 |
| 2019 December | 59 | 13 | 72 |
| 2019 November | 72 | 5 | 77 |
| 2019 October | 41 | 4 | 45 |
| 2019 September | 69 | 10 | 79 |
| 2019 August | 49 | 10 | 59 |
| 2019 July | 40 | 14 | 54 |
| 2019 June | 59 | 5 | 64 |
| 2019 May | 34 | 2 | 36 |
| 2019 April | 84 | 12 | 96 |
| 2019 March | 46 | 12 | 58 |
| 2019 February | 36 | 6 | 42 |
| 2019 January | 44 | 14 | 58 |
| 2018 December | 105 | 23 | 128 |
| 2018 November | 97 | 14 | 111 |
| 2018 October | 121 | 14 | 135 |
| 2018 September | 88 | 11 | 99 |
| 2018 August | 52 | 12 | 64 |
| 2018 July | 60 | 8 | 68 |
| 2018 June | 57 | 17 | 74 |
| 2018 May | 56 | 13 | 69 |
| 2018 April | 62 | 6 | 68 |
| 2018 March | 40 | 10 | 50 |
| 2018 February | 54 | 6 | 60 |
| 2018 January | 50 | 10 | 60 |
| 2017 December | 46 | 9 | 55 |
| 2017 November | 55 | 6 | 61 |
| 2017 October | 42 | 14 | 56 |
| 2017 September | 37 | 10 | 47 |
| 2017 August | 37 | 10 | 47 |
| 2017 July | 35 | 11 | 46 |
| 2017 June | 46 | 6 | 52 |
| 2017 May | 61 | 14 | 75 |
| 2017 April | 36 | 7 | 43 |
| 2017 March | 31 | 5 | 36 |
| 2017 February | 22 | 8 | 30 |
| 2017 January | 29 | 9 | 38 |
| 2016 December | 36 | 11 | 47 |
| 2016 November | 54 | 13 | 67 |
| 2016 October | 79 | 15 | 94 |
| 2016 September | 122 | 3 | 125 |
| 2016 August | 172 | 0 | 172 |
| 2016 July | 146 | 0 | 146 |
| 2016 June | 118 | 0 | 118 |
| 2016 May | 96 | 0 | 96 |
| 2016 April | 73 | 0 | 73 |
| 2016 March | 50 | 0 | 50 |
| 2016 February | 75 | 0 | 75 |
| 2016 January | 74 | 0 | 74 |
| 2015 December | 94 | 0 | 94 |
| 2015 November | 72 | 0 | 72 |
| 2015 October | 83 | 0 | 83 |
| 2015 September | 72 | 0 | 72 |
| 2015 August | 73 | 0 | 73 |
| 2015 July | 59 | 0 | 59 |
| 2015 June | 29 | 0 | 29 |
| 2015 May | 55 | 0 | 55 |
| 2015 April | 11 | 0 | 11 |
Show all
