An Interdisciplinary Diagnostic Approach to Guide Therapy in C3 Glomerulopathy
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An Interdisciplinary Diagnostic Approach to Guide Therapy in C3 Glomerulopathy. / Schmidt, Tilman; Afonso, Sara; Perie, Luce; Heidenreich, Karin; Wulf, Sonia; Krebs, Christian F; Zipfel, Peter F; Wiech, Thorsten.
in: FRONT IMMUNOL, Jahrgang 13, 826513, 2022.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - An Interdisciplinary Diagnostic Approach to Guide Therapy in C3 Glomerulopathy
AU - Schmidt, Tilman
AU - Afonso, Sara
AU - Perie, Luce
AU - Heidenreich, Karin
AU - Wulf, Sonia
AU - Krebs, Christian F
AU - Zipfel, Peter F
AU - Wiech, Thorsten
N1 - Copyright © 2022 Schmidt, Afonso, Perie, Heidenreich, Wulf, Krebs, Zipfel and Wiech.
PY - 2022
Y1 - 2022
N2 - Since the re-classification of membranoproliferative glomerulonephritis the new disease entity C3 glomerulopathy is diagnosed if C3 deposition is clearly dominant over immunoglobulins in immunohistochemistry or immunofluorescence. Although this new definition is more orientated at the pathophysiology as mediated by activity of the alternative complement pathway C3 glomerulopathy remains a heterogenous group of disorders. Genetic or autoimmune causes are associated in several but not in all patients with this disease. However, prognosis is poorly predictable, and clinicians cannot directly identify patients that might benefit from therapy. Moreover, therapy may range from supportive care alone, unspecific immune suppression, plasma treatment, or plasma exchange to complement inhibition. The current biopsy based diagnostic approaches sometimes combined with complement profiling are not sufficient to guide clinicians neither (i) whether to treat an individual patient, nor (ii) to choose the best therapy. With this perspective, we propose an interdisciplinary diagnostic approach, including detailed analysis of the kidney biopsy for morphological alterations and immunohistochemical staining, for genetic analyses of complement genes, complement activation patterning in plasma, and furthermore for applying novel approaches for convertase typing and complement profiling directly in renal tissue. Such a combined diagnostic approach was used here for a 42-year-old female patient with a novel mutation in the Factor H gene, C3 glomerulopathy and signs of chronic endothelial damage. We present here an approach that might in future help to guide therapy of renal diseases with relevant complement activation, especially since diverse new anti-complement agents are under clinical investigation.
AB - Since the re-classification of membranoproliferative glomerulonephritis the new disease entity C3 glomerulopathy is diagnosed if C3 deposition is clearly dominant over immunoglobulins in immunohistochemistry or immunofluorescence. Although this new definition is more orientated at the pathophysiology as mediated by activity of the alternative complement pathway C3 glomerulopathy remains a heterogenous group of disorders. Genetic or autoimmune causes are associated in several but not in all patients with this disease. However, prognosis is poorly predictable, and clinicians cannot directly identify patients that might benefit from therapy. Moreover, therapy may range from supportive care alone, unspecific immune suppression, plasma treatment, or plasma exchange to complement inhibition. The current biopsy based diagnostic approaches sometimes combined with complement profiling are not sufficient to guide clinicians neither (i) whether to treat an individual patient, nor (ii) to choose the best therapy. With this perspective, we propose an interdisciplinary diagnostic approach, including detailed analysis of the kidney biopsy for morphological alterations and immunohistochemical staining, for genetic analyses of complement genes, complement activation patterning in plasma, and furthermore for applying novel approaches for convertase typing and complement profiling directly in renal tissue. Such a combined diagnostic approach was used here for a 42-year-old female patient with a novel mutation in the Factor H gene, C3 glomerulopathy and signs of chronic endothelial damage. We present here an approach that might in future help to guide therapy of renal diseases with relevant complement activation, especially since diverse new anti-complement agents are under clinical investigation.
KW - Adult
KW - Complement Activation
KW - Complement C3
KW - Complement Pathway, Alternative/genetics
KW - Female
KW - Glomerulonephritis, Membranoproliferative/diagnosis
KW - Humans
KW - Immunoglobulins/therapeutic use
U2 - 10.3389/fimmu.2022.826513
DO - 10.3389/fimmu.2022.826513
M3 - SCORING: Journal article
C2 - 35693785
VL - 13
JO - FRONT IMMUNOL
JF - FRONT IMMUNOL
SN - 1664-3224
M1 - 826513
ER -