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3. Utility of serum complement factors C3 and C4 as biomarkers during therapeutic management of giant cell arteritis.

Author

Conticini, E, Hellmich, B, Frediani, B, Csernok, E, and Löffler, C

Subjects
BLOOD sedimentation, GIANT cell arteritis, BIOMARKERS, C-reactive protein
Abstract

There is a strong unmet need for biomarkers in giant cell arteritis (GCA), as C-reactive protein (CRP) may be unreliable in patients treated with Tocilizumab (TCZ). We aimed to assess whether C3 and C4 are useful biomarkers in GCA patients, particularly in those treated with TCZ. We retrospectively enrolled all patients who underwent C3 and C4 measurement at baseline. All patients were evaluated at 3, 6, 12, and 24 months after diagnosis, as part of routine follow-up. Two assessments after the end of the observational period, in case of further relapses, were also included. At baseline, mean ± sd levels (mg/dL) of C3 (133 ± 28.99) and C4 (25.9 ± 9.04) were within normal ranges. During follow-up, C3 and C4 decreased in patients attaining remission (107.07 ± 19.86, p = 0.0006; 19.86 ± 10.27, p = 0.01, respectively) and sustained remission (95.85 ± 18.04, p = 0.001; 15.61 ± 9.75, p = 0.006). In TCZ-treated patients, even stronger decreases in C3 (83.11 ± 19.66, p = 0.001) and C4 (8.26 ± 3.83, p < 0.0001) were observed, and their values were not correlated with CRP or erythrocyte sedimentation rate. C3 and C4 do not seem useful in the diagnosis of GCA, as normal values do not rule out active vasculitis. However, C3 and C4 correlate with disease activity. As the low C4 levels found in TCZ-treated patients are not correlated with CRP, C4 should be evaluated as a potential biomarker of disease activity and treatment response. [ABSTRACT FROM AUTHOR]

Published
2023
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9. Wachstumsfaktoren und Zytokine in der inneren Medizin

Author

Habenicht, A., Habenicht, A. J. R., Janßen-Timmen, U., Salbach, P. B., Blattner, Ch., Ziegler, R., Gross, W. L., Csernok, E., Kekow, J., Steffen, M., Witthöft, Th., Schreiber, S., Raedler, A., Reinecker, C., Schweigerer, L., Nawroth, P. P., Bierhaus, A., Lin, J., Zhang, Y., Stahl, R., and Miehlke, Klaus, editor

Published
1991
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10. Harmonization of antineutrophil cytoplasmic antibodies (ANCA) testing by reporting test result-specific likelihood ratios: position paper

Author

Bossuyt, X., Bossuyt, X., Damoiseaux, J., Rasmussen, N., van Paassen, P., Hellmich, B., Baslund, B., Blockmans, D., Vermeersch, P., Lopez-Hoyos, M., Vercammen, M., Barret, E., Hammar, F., Leinfelder, U., Mahler, M., Olschowka, N., Roggenbuck, D., Schlumberger, W., Walker, R., Ronnelid, J., Tervaert, J.W.C., Csernok, E., Fierz, W., European Federation of Laboratory Medicine (EFLM) Task and Finish Group “Autoimmunity Testing”, European Autoimmune Standardization Initiative (EASI), European Consensus Finding Study Group on autoantibodies (ECFSG), Bossuyt, X., Bossuyt, X., Damoiseaux, J., Rasmussen, N., van Paassen, P., Hellmich, B., Baslund, B., Blockmans, D., Vermeersch, P., Lopez-Hoyos, M., Vercammen, M., Barret, E., Hammar, F., Leinfelder, U., Mahler, M., Olschowka, N., Roggenbuck, D., Schlumberger, W., Walker, R., Ronnelid, J., Tervaert, J.W.C., Csernok, E., Fierz, W., European Federation of Laboratory Medicine (EFLM) Task and Finish Group “Autoimmunity Testing”, European Autoimmune Standardization Initiative (EASI), and European Consensus Finding Study Group on autoantibodies (ECFSG)

Published
2021

12. International consensus on antineutrophil cytoplasm antibodies testing in eosinophilic granulomatosis with polyangiitis

Author

Moiseev, S. Bossuyt, X. Arimura, Y. Blockmans, D. Csernok, E. Damoiseaux, J. Emmi, G. Flores-Suarez, L.F. Hellmich, B. Jayne, D. Charles Jennette, J. Little, M.A. Mohammad, A.J. Moosig, F. Novikov, P. Pagnoux, C. Radice, A. Sada, K.-e. Segelmark, M. Shoenfeld, Y. Sinico, R.A. Specks, U. Terrier, B. Tzioufas, A.G. Vaglio, A. Zhao, M.-H. Tervaert, J.C.

Subjects
immune system diseases, cardiovascular diseases, urologic and male genital diseases, skin and connective tissue diseases, respiratory tract diseases
Abstract

An international consensus on antineutrophil cytoplasm antibodies (ANCA) testing in eosinophilic granulomatosiswith polyangiitis (EGPA) is presented.ANCA, specific formyeloperoxidase (MPO), can be detected in 30-35% of patients with EGPA. MPO-ANCA should be tested with antigen-specific immunoassays in any patient with eosinophilic asthma and clinical features suggesting EGPA, including constitutional symptoms; purpura; polyneuropathy; unexplained heart, gastrointestinal, or kidney disease; and/or pulmonary infiltrates or hemorrhage.Apositive MPO-ANCA result contributes to the diagnostic workup for EGPA. Patients with MPO-ANCA-associated EGPA have vasculitis features, such as glomerulonephritis, neuropathy, and skin manifestations, more frequently than patients with ANCA-negative EGPA. However, the presence of MPO-ANCA is neither sensitive nor specific enough to identifywhether a patient should be subclassified as having "vasculitic"or "eosinophilic"EGPA. At present, ANCA status cannot guide treatment decisions, that is,whether cyclophosphamide, rituximab, ormepolizumab should be added to conventional glucocorticoid treatment. In EGPA, monitoring of ANCA is only useful when MPO-ANCA was tested positive at disease onset. © 2020 by the American Thoracic Society.

Published
2020

13. 2020 international consensus on ANCA testing beyond systemic vasculitis

Author

Moiseev, S. Cohen Tervaert, J.W. Arimura, Y. Bogdanos, D.P. Csernok, E. Damoiseaux, J. Ferrante, M. Flores-Suárez, L.F. Fritzler, M.J. Invernizzi, P. Jayne, D. Jennette, J.C. Little, M.A. McAdoo, S.P. Novikov, P. Pusey, C.D. Radice, A. Salama, A.D. Savige, J.A. Segelmark, M. Shoenfeld, Y. Sinico, R.A. Sousa, M.-J. Specks, U. Terrier, B. Tzioufas, A.G. Vermeire, S. Zhao, M.-H. Bossuyt, X.

Subjects
immune system diseases, cardiovascular diseases, skin and connective tissue diseases, urologic and male genital diseases, respiratory tract diseases
Abstract

This document follows up on a 2017 revised international consensus on anti-neutrophil cytoplasm antibodies (ANCA) testing in granulomatosis with polyangiitis and microscopic polyangiitis and focuses on the clinical and diagnostic value of ANCA detection in patients with connective tissue diseases, idiopathic interstitial pneumonia, autoimmune liver diseases, inflammatory bowel diseases, anti-glomerular basement membrane (GBM) disease, infections, malignancy, and during drug treatment. Current evidence suggests that in certain settings beyond systemic vasculitis, ANCA may have clinical, pathogenic and/or diagnostic relevance. Antigen-specific ANCA targeting proteinase-3 and myeloperoxidase should be tested by solid phase immunoassays in any patient with clinical features suggesting ANCA-associated vasculitis and in all patients with anti-GBM disease, idiopathic interstitial pneumonia, and infective endocarditis associated with nephritis, whereas in patients with other aforementioned disorders routine ANCA testing is not recommended. Among patients with autoimmune liver diseases or inflammatory bowel diseases, ANCA testing may be justified in patients with suspected autoimmune hepatitis type 1 who do not have conventional autoantibodies or in case of diagnostic uncertainty to discriminate ulcerative colitis from Crohn's disease. In these cases, ANCA should be tested by indirect immunofluorescence as the target antigens are not yet well characterized. Many questions concerning the optimal use of ANCA testing in patients without ANCA-associated vasculitis remain to be answered. © 2020 Elsevier B.V.

Published
2020

14. International Consensus on ANCA Testing in Eosinophilic Granulomatosis with Polyangiitis

Author

Moiseev, S, Bossuyt, X, Arimura, Y, Blockmans, D, Csernok, E, Damoiseaux, J, Emmi, G, Flores-Suárez, L, Hellmich, B, Jayne, D, Jennette, J, Little, M, Mohammad, A, Moosig, F, Novikov, P, Pagnoux, C, Radice, A, Sada, K, Segelmark, M, Shoenfeld, Y, Sinico, R, Specks, U, Terrier, B, Tzioufas, A, Vaglio, A, Zhao, M, Cohen Tervaert, J, Moiseev, Sergey, Bossuyt, Xavier, Arimura, Yoshihiro, Blockmans, Daniel, Csernok, Elena, Damoiseaux, Jan, Emmi, Giacomo, Flores-Suárez, Luis Felipe, Hellmich, Bernhard, Jayne, David, Jennette, J Charles, Little, Mark A, Mohammad, Aladdin J, Moosig, Frank, Novikov, Pavel, Pagnoux, Christian, Radice, Antonella, Sada, Ken-Ei, Segelmark, Mårten, Shoenfeld, Yehuda, Sinico, Renato A, Specks, Ulrich, Terrier, Benjamin, Tzioufas, Athanasios G, Vaglio, Augusto, Zhao, Ming-Hui, Cohen Tervaert, Jan Willem, Moiseev, S, Bossuyt, X, Arimura, Y, Blockmans, D, Csernok, E, Damoiseaux, J, Emmi, G, Flores-Suárez, L, Hellmich, B, Jayne, D, Jennette, J, Little, M, Mohammad, A, Moosig, F, Novikov, P, Pagnoux, C, Radice, A, Sada, K, Segelmark, M, Shoenfeld, Y, Sinico, R, Specks, U, Terrier, B, Tzioufas, A, Vaglio, A, Zhao, M, Cohen Tervaert, J, Moiseev, Sergey, Bossuyt, Xavier, Arimura, Yoshihiro, Blockmans, Daniel, Csernok, Elena, Damoiseaux, Jan, Emmi, Giacomo, Flores-Suárez, Luis Felipe, Hellmich, Bernhard, Jayne, David, Jennette, J Charles, Little, Mark A, Mohammad, Aladdin J, Moosig, Frank, Novikov, Pavel, Pagnoux, Christian, Radice, Antonella, Sada, Ken-Ei, Segelmark, Mårten, Shoenfeld, Yehuda, Sinico, Renato A, Specks, Ulrich, Terrier, Benjamin, Tzioufas, Athanasios G, Vaglio, Augusto, Zhao, Ming-Hui, and Cohen Tervaert, Jan Willem

Abstract

An international consensus on anti-neutrophil cytoplasm antibodies (ANCA) testing in eosinophilic granulomatosis with polyangiitis (EGPA) is presented. ANCA, specific for myeloperoxidase (MPO), can be detected in 30-35% of EGPA patients. MPO-ANCA should be tested with antigen-specific immunoassays in any patient with eosinophilic asthma and clinical features suggesting EGPA, including constitutional symptoms, purpura, polyneuropathy, unexplained heart, gastrointestinal or kidney disease, and/or pulmonary infiltrates or hemorrhage. A positive MPO-ANCA result contributes to the diagnostic work‑up for EGPA. Patients with MPO-ANCA associated EGPA have more frequently vasculitis features, such as glomerulonephritis, neuropathy, and skin manifestations than patients with ANCA negative EGPA. However, the presence of MPO-ANCA is neither sensitive nor specific enough to identify whether a patient should be subclassified as having "vasculitic" or "eosinophilic" EGPA. At present, ANCA status cannot guide treatment decisions, that is, whether cyclophosphamide, rituximab or mepolizumab should be added to conventional glucocorticoid treatment. In EGPA, monitoring of ANCA is only useful when MPO-ANCA was tested positive at disease onset.

Published
2020

15. 2020 international consensus on ANCA testing beyond systemic vasculitis

Author

Moiseev, S, Tervaert, J, Arimura, Y, Bogdanos, D, Csernok, E, Damoiseaux, J, Ferrante, M, Flores-Suárez, L, Fritzler, M, Invernizzi, P, Jayne, D, Jennette, J, Little, M, Mcadoo, S, Novikov, P, Pusey, C, Radice, A, Salama, A, Savige, J, Segelmark, M, Shoenfeld, Y, Sinico, R, Sousa, M, Specks, U, Terrier, B, Tzioufas, A, Vermeire, S, Zhao, M, Bossuyt, X, Moiseev, Sergey, Tervaert, Jan Willem Cohen, Arimura, Yoshihiro, Bogdanos, Dimitrios P., Csernok, Elena, Damoiseaux, Jan, Ferrante, Marc, Flores-Suárez, Luis Felipe, Fritzler, Marvin J., Invernizzi, Pietro, Jayne, David, Jennette, J. Charles, Little, Mark, McAdoo, Stephen P., Novikov, Pavel, Pusey, Charles D., Radice, Antonella, Salama, Alan D., Savige, Judith A., Segelmark, Mårten, Shoenfeld, Yehuda, Sinico, Renato A., Sousa, Maria-José, Specks, Ulrich, Terrier, Benjamin, Tzioufas, Athanasios G., Vermeire, Severine, Zhao, Ming-Hui, Bossuyt, Xavier, Moiseev, S, Tervaert, J, Arimura, Y, Bogdanos, D, Csernok, E, Damoiseaux, J, Ferrante, M, Flores-Suárez, L, Fritzler, M, Invernizzi, P, Jayne, D, Jennette, J, Little, M, Mcadoo, S, Novikov, P, Pusey, C, Radice, A, Salama, A, Savige, J, Segelmark, M, Shoenfeld, Y, Sinico, R, Sousa, M, Specks, U, Terrier, B, Tzioufas, A, Vermeire, S, Zhao, M, Bossuyt, X, Moiseev, Sergey, Tervaert, Jan Willem Cohen, Arimura, Yoshihiro, Bogdanos, Dimitrios P., Csernok, Elena, Damoiseaux, Jan, Ferrante, Marc, Flores-Suárez, Luis Felipe, Fritzler, Marvin J., Invernizzi, Pietro, Jayne, David, Jennette, J. Charles, Little, Mark, McAdoo, Stephen P., Novikov, Pavel, Pusey, Charles D., Radice, Antonella, Salama, Alan D., Savige, Judith A., Segelmark, Mårten, Shoenfeld, Yehuda, Sinico, Renato A., Sousa, Maria-José, Specks, Ulrich, Terrier, Benjamin, Tzioufas, Athanasios G., Vermeire, Severine, Zhao, Ming-Hui, and Bossuyt, Xavier

Abstract

This document follows up on a 2017 revised international consensus on anti-neutrophil cytoplasm antibodies (ANCA) testing in granulomatosis with polyangiitis and microscopic polyangiitis and focuses on the clinical and diagnostic value of ANCA detection in patients with connective tissue diseases, idiopathic interstitial pneumonia, autoimmune liver diseases, inflammatory bowel diseases, anti-glomerular basement membrane (GBM) disease, infections, malignancy, and during drug treatment. Current evidence suggests that in certain settings beyond systemic vasculitis, ANCA may have clinical, pathogenic and/or diagnostic relevance. Antigen-specific ANCA targeting proteinase-3 and myeloperoxidase should be tested by solid phase immunoassays in any patient with clinical features suggesting ANCA-associated vasculitis and in all patients with anti-GBM disease, idiopathic interstitial pneumonia, and infective endocarditis associated with nephritis, whereas in patients with other aforementioned disorders routine ANCA testing is not recommended. Among patients with autoimmune liver diseases or inflammatory bowel diseases, ANCA testing may be justified in patients with suspected autoimmune hepatitis type 1 who do not have conventional autoantibodies or in case of diagnostic uncertainty to discriminate ulcerative colitis from Crohn's disease. In these cases, ANCA should be tested by indirect immunofluorescence as the target antigens are not yet well characterized. Many questions concerning the optimal use of ANCA testing in patients without ANCA-associated vasculitis remain to be answered.

Published
2020

24. Revised 2017 international consensus on testing of ANCAs in granulomatosis with polyangiitis and microscopic polyangiitis [Position paper]

Author

Bossuyt, X, Cohen Tervaert, J, Arimura, Y, Blockmans, D, Flores Suárez, L, Guillevin, L, Hellmich, B, Jayne, D, Jennette, J, Kallenberg, C, Moiseev, S, Novikov, P, Radice, A, Savige, J, Sinico, R, Specks, U, van Paassen, P, Zhao, M, Rasmussen, N, Damoiseaux, J, Csernok, E, SINICO, RENATO ALBERTO, Csernok, E., Bossuyt, X, Cohen Tervaert, J, Arimura, Y, Blockmans, D, Flores Suárez, L, Guillevin, L, Hellmich, B, Jayne, D, Jennette, J, Kallenberg, C, Moiseev, S, Novikov, P, Radice, A, Savige, J, Sinico, R, Specks, U, van Paassen, P, Zhao, M, Rasmussen, N, Damoiseaux, J, Csernok, E, SINICO, RENATO ALBERTO, and Csernok, E.

Abstract

Anti-neutrophil cytoplasmic antibodies (ANCAs) are valuable laboratory markers used for the diagnosis of well-defined types of small-vessel vasculitis, including granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). According to the 1999 international consensus on ANCA testing, indirect immunofluorescence (IIF) should be used to screen for ANCAs, and samples containing ANCAs should then be tested by immunoassays for proteinase 3 (PR3)-ANCAs and myeloperoxidase (MPO)-ANCAs. The distinction between PR3-ANCAs and MPO-ANCAs has important clinical and pathogenic implications. As dependable immunoassays for PR3-ANCAs and MPO-ANCAs have become broadly available, there is increasing international agreement that high-quality immunoassays are the preferred screening method for the diagnosis of ANCA-associated vasculitis. The present Consensus Statement proposes that high-quality immunoassays can be used as the primary screening method for patients suspected of having the ANCA-associated vaculitides GPA and MPA without the categorical need for IIF, and presents and discusses evidence to support this recommendation.

Published
2017

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