Antibodies against C1q in patients with systemic lupus erythematosus

The first component of the classical pathway of complement (C1q) is considered to be involved in the pathogenesis of systemic lupus erythematosus (SLE). This view is based on the observation that a substantial number of patients with SLE develop hypocomplementemia with depletion of the classical pathway components, and C1q has been shown to play an important role in the clearance of immune complexes and apoptotic bodies. In addition, homozygous C1q deficiency is the strongest disease susceptibility gene for the development of SLE that has been characterised in humans. However, most SLE patients have no primary complement deficiency. Hypocomplementemia in SLE patients is a secondary event and often associated with antibodies against C1q (anti-C1q). Although anti-C1q have been found in a number of distinct autoimmune disorders, they are best described in patients with SLE where they strongly correlate with renal flares. Current data suggest that the occurrence of anti-C1q in SLE patients is necessary but not sufficient for the development of proliferative lupus nephritis, suggesting an interference with the normal function of the complement syste

Evaluation of the therapeutic potential of ant-TLR4-antibody MTS510 in experimental stroke and significa of different routes of application

Toll-like receptors (TLRs) are central sensors for the inflammatory response in ischemia-reperfusion injury. We therefore investigated whether TLR4 inhibition could be used to treat stroke in a standard model of focal cerebral ischemia. Anti-TLR4/MD2-antibody (mAb clone MTS510) blocked TLR4-induced cell activation in vitro, as reported previously. Here, different routes of MTS510 application in vivo were used to study the effects on stroke outcome up to 2d after occlusion of the middle cerebral artery (MCAO) for 45 min in adult male C57Bl/6 wild-type mice. Improved neurological performance, reduced infarct volumes, and reduced brain swelling showed that intravascular application of MTS510 had a protective effect in the model of 45 min MCAO. Evaluation of potential long-term adverse effects of anti-TLR4-mAb-treament revealed no significant deleterious effect on infarct volumes nor neurological deficit after 14d of reperfusion in a mild model of stroke (15 min MCAO). Interestingly, inhibition of TLR4 resulted in an altered adaptive immune response at 48 hours after reperfusion. We conclude that blocking TLR4 by the use of specific mAb is a promising strategy for stroke therapy. However, long-term studies with increased functional sensitivity, larger sampling sizes and use of other species are required before a clinical use could be envisaged

Primary cytomegalovirus infection with accompanying Pneumocystis jiroveci pneumonia in a patient with large-vessel vasculitis

A 70year-old female patient presented with fever, nausea and dyspnea. She had been receiving immunosuppressive therapy with methotrexate and prednisone for large-vessel vasculitis. The patient was shown to have coexistent Pneumocystis jiroveci pneumonia and primary cytomegalovirus (CMV) infection with presumed CMV pneumonitis and colitis. To our knowledge, this is the first case report on the occurrence of combined primary cytomegalovirus and Pneumocystis jiroveci infection in a patient with vasculitis. It illustrates the importance of being aware of the possibility of combined opportunistic infections in patients with rheumatologic disease

Assessment of the Therapeutic Potential of Metallothionein-II Application in Focal Cerebral Ischemia In Vitro and In Vivo

Metallothionein-II (MT-II) is an ubiquitously expressed small-molecular-weight protein and highly induced in various species and tissues upon stress, inflammation, and ischemia. MT-deficiency exacerbates ischemic injury in rodent stroke models in vitro and in vivo. However, there is conflicting data on the potential neuroprotective effect of exogenously applied metallothionein. Thus, we applied MT-II in an in vitro stroke model and intraperitoneally (i.p.) in two in vivo standard models of transient middle cerebral artery occlusion (MCAO) (a ‘stringent’ one [60min MCAO/48h reperfusion] and a ‘mild’ one [30min MCAO/72h reperfusion]), as well as i.v. together with recombinant tissue plasminogen activator (rtPA) to evaluate if exogenous MT-II-application protects against ischemic stroke. Whereas MT-II did not protect against 60min MCAO, there was a significant reduction of direct and indirect infarct volumes and neurological deficit in the MT-II (i.p.) treated animals in the ‘mild’ model at 3d after MCAO. Furthermore, MT- II also improved survival of the mice after MCAO, suppressed TNF-α mRNA induction in ischemic brain tissue, and protected primary neuronal cells against oxygen-glucose-deprivation in vitro. Thus, exogenous application of MT-II protects against ischemic injury in vitro and in vivo. However, long- term studies with different species and larger sampling sizes are required before a clinical use can be envisaged

Zur Operation der Embolie der Lungenarterie

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Heterogeneity of spacer lengths in circles of amplified ribosomal DNA of two insect species, Dytiscus marginalis and Acheta domesticus

No abstract availabl

Kombiniert-heterozygote Defizienz von Komplementfaktor C7 bei einerPatientin mit rezidivierender Meningitis

Zusammenfassung: Hintergrund:: Die Assoziation zwischen Komplementdefizienzen, insbesondere von Komponenten der terminalen Kaskade (C5-C9), und dem Auftreten von Meningokokkeninfekten und bakteriellen Meningitiden ist gut beschrieben. Fallbeschreibung:: In dem vorliegenden Fallbericht wird dabei erstmals ein kombiniert-heterozygoter Defekt im C7-Gen beschrieben, der noch eine Restproduktion von C7 erlaubte. Diese Restproduktion reichte jedoch nicht aus, um vor rezidivierenden Meningitiden zu schützen. Schlussfolgerung:: Der Fallbericht zeigt erneut den Stellenwert der Komplementdiagnostik bei Patienten mit Meningokokkeninfekt und die Notwendigkeit, auch Patienten mit reduzierter, aber noch messbarer Komplementaktivität einer weiteren Abklärung auf eine Komplementdefizienz zuzuführe

Targeting thromboinflammation in COVID-19 - A narrative review of the potential of C1 inhibitor to prevent disease progression.

Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 is associated with a clinical spectrum ranging from asymptomatic carriers to critically ill patients with complications including thromboembolic events, myocardial injury, multisystemic inflammatory syndromes and death. Since the beginning of the pandemic several therapeutic options emerged, with a multitude of randomized trials, changing the medical landscape of COVID-19. The effect of various monoclonal antibodies, antiviral, anti-inflammatory and anticoagulation drugs have been studied, and to some extent, implemented into clinical practice. In addition, a multitude of trials improved the understanding of the disease and emerging evidence points towards a significant role of the complement system, kallikrein-kinin, and contact activation system as drivers of disease in severe COVID-19. Despite their involvement in COVID-19, treatments targeting these plasmatic cascades have neither been systematically studied nor introduced into clinical practice, and randomized studies with regards to these treatments are scarce. Given the multiple-action, multiple-target nature of C1 inhibitor (C1-INH), the natural inhibitor of these cascades, this drug may be an interesting candidate to prevent disease progression and combat thromboinflammation in COVID-19. This narrative review will discuss the current evidence with regards to the involvement of these plasmatic cascades as well as endothelial cells in COVID-19. Furthermore, we summarize the evidence of C1-INH in COVID-19 and potential benefits and pitfalls of C1-INH treatment in COVID-19