Ectosomes as immunomodulators

Considerable progress has been made in recognizing microvesicles as important mediators of intercellular communication rather than irrelevant cell debris. Microvesicles released by budding directly from the cell membrane surface (i.e., ectocytosis) either spontaneously or in response to various stimuli are called shed vesicles or ectosomes. Ectosomes are rightside-out vesicles with cytosolic content, and they expose phosphatidylserine in the outer leaflet of their membrane. Depending on their cellular origin, ectosomes have been associated with a broad spectrum of biological activities. In the light of recent findings, we now know that ectosomes derived from polymorphonuclear leukocytes, erythrocytes, platelets, and tumor cells have profound effects on the innate immune system, as well as on the induction of the adaptive immunity, globally reprogramming cells such as macrophages or dendritic cells toward an immunosuppressive and possibly tolerogenic phenotype. Although the effects observed in the circulation are mainly procoagulant and pro-inflammatory, ectosomes might be anti-inflammatory/immunosuppressive in local inflammatio

Atypical hemolytic uremic syndrome : update on the complement system and what is new

Atypical hemolytic uremic syndrome (aHUS) is a rare disease of microangiopathic hemolytic anemia, thrombocytopenia, and predominant renal impairment. It is characterized by the absence of Shiga toxin-producing bacteria as a triggering factor. During the last decade, aHUS has been demonstrated to be a disorder of the complement alternative pathway dysregulation, as there is a growing list of mutations and polymorphisms in the genes encoding the complement regulatory proteins that alone or in combination may lead to aHUS. Approximately 60% of aHUS patients have so-called 'loss-of-function' mutations in the genes encoding the complement regulatory proteins, which normally protect host cells from complement activation: complement factor H (CFH), factor I (CFI) and membrane cofactor protein (MCP or CD46), or have 'gain-of-function' mutations in the genes encoding the complement factor B or C3. In addition, approximately 10% of aHUS patients have a functional CFH deficiency due to anti-CFH antibodies. Recent advances in understanding the pathogenesis of aHUS have led to a revised classification of the syndrome. Normal plasma levels of CFH and CFI do not preclude the presence of a mutation in these genes. Further, genotype-phenotype correlations of aHUS have clinical significance in predicting renal recovery and transplant outcome. Therefore, it is important to make a comprehensive analysis and perform genetic screening of the complement system in patients with aHUS to allow a more precise approach, especially before transplantation. This may also provide opportunities for more specific treatments in the near future, as complement inhibition could represent a therapeutic target in these patients who have a considerably poor prognosis in terms of both mortality and progression to end-stage renal disease and a great risk of disease recurrence after transplantation

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