Complement Activation in Kidneys of Patients With COVID-19
Autor: | Klaus Überla, Tajana Ries, Hans-Martin Jäck, Christoph Daniel, Frederick Pfister, Ahmed Sheriff, Maike Büttner-Herold, Günter Lochnit, Kerstin Amann, Eva Vonbrunn, Martin Herrmann |
---|---|
Rok vydání: | 2021 |
Předmět: |
lcsh:Immunologic diseases. Allergy
Adult Male 0301 basic medicine kidney Pathology medicine.medical_specialty complement—immunological term Immunology 030204 cardiovascular system & hematology Peritubular capillaries 03 medical and health sciences Classical complement pathway 0302 clinical medicine medicine Humans Immunology and Allergy ddc:610 Complement Activation Original Research Aged Disseminated intravascular coagulation Kidney SARS-CoV-2 business.industry COVID-19 endothelial injury Acute Kidney Injury Middle Aged medicine.disease lectin pathway activation Complement system 030104 developmental biology medicine.anatomical_structure Lectin pathway Alternative complement pathway Female lcsh:RC581-607 Complement membrane attack complex business |
Zdroj: | Frontiers in Immunology Frontiers in Immunology, Vol 11 (2021) |
ISSN: | 1664-3224 |
Popis: | Most patients who became critically ill following infection with COVID-19 develop severe acute respiratory syndrome (SARS) attributed to a maladaptive or inadequate immune response. The complement system is an important component of the innate immune system that is involved in the opsonization of viruses but also in triggering further immune cell responses. Complement activation was seen in plasma adsorber material that clogged during the treatment of critically ill patients with COVID-19. Apart from the lung, the kidney is the second most common organ affected by COVID-19. Using immunohistochemistry for complement factors C1q, MASP-2, C3c, C3d, C4d, and C5b-9 we investigated the involvement of the complement system in six kidney biopsies with acute kidney failure in different clinical settings and three kidneys from autopsy material of patients with COVID-19. Renal tissue was analyzed for signs of renal injury by detection of thrombus formation using CD61, endothelial cell rarefaction using the marker E-26 transformation specific-related gene (ERG-) and proliferation using proliferating cell nuclear antigen (PCNA)-staining. SARS-CoV-2 was detected by in situ hybridization and immunohistochemistry. Biopsies from patients with hemolytic uremic syndrome (HUS, n = 5), severe acute tubular injury (ATI, n = 7), zero biopsies with disseminated intravascular coagulation (DIC, n = 7) and 1 year protocol biopsies from renal transplants (Ctrl, n = 7) served as controls. In the material clogging plasma adsorbers used for extracorporeal therapy of patients with COVID-19 C3 was the dominant protein but collectin 11 and MASP-2 were also identified. SARS-CoV-2 was sporadically present in varying numbers in some biopsies from patients with COVID-19. The highest frequency of CD61-positive platelets was found in peritubular capillaries and arteries of COVID-19 infected renal specimens as compared to all controls. Apart from COVID-19 specimens, MASP-2 was detected in glomeruli with DIC and ATI. In contrast, the classical pathway (i.e. C1q) was hardly seen in COVID-19 biopsies. Both C3 cleavage products C3c and C3d were strongly detected in renal arteries but also occurs in glomerular capillaries of COVID-19 biopsies, while tubular C3d was stronger than C3c in biopsies from COVID-19 patients. The membrane attack complex C5b-9, demonstrating terminal pathway activation, was predominantly deposited in COVID-19 biopsies in peritubular capillaries, renal arterioles, and tubular basement membrane with similar or even higher frequency compared to controls. In conclusion, various complement pathways were activated in COVID-19 kidneys, the lectin pathway mainly in peritubular capillaries and in part the classical pathway in renal arteries whereas the alternative pathway seem to be crucial for tubular complement activation. Therefore, activation of the complement system might be involved in the worsening of renal injury. Complement inhibition might thus be a promising treatment option to prevent deregulated activation and subsequent collateral tissue injury. |
Databáze: | OpenAIRE |
Externí odkaz: |