Background: Complement (C) can be activated during malaria, C components consumed and inflammatory mediators produced. This has potential to impair host innate defence.
Methods: In a case-control study, C activation was assessed by measuring serum haemolytic activity (CH50), functional activity of each pathway and levels of C3a, C4a and C5a in children presenting at Kisumu District Hospital, western Kenya, with severe malarial anaemia (SMA) or uncomplicated malaria (UM).
Results: CH50 median titers for lysis of sensitized sheep erythrocytes in SMA (8.6 U/mL) were below normal (34-70 U/mL) and were one-fourth the level in UM (34.6 U/mL (P < 0.001). Plasma C3a median levels were 10 times higher than in normals forSMA (3,200 ng/ml) and for UM (3,500 ng/ml), indicating substantial C activation in both groups. Similar trends were obtained for C4a and C5a. The activities of all three C pathways were greatly reduced in SMA compared to UM (9.9% vs 83.4% for CP, 0.09% vs 30.7% for MBL and 36.8% vs 87.7% for AP respectively, P < 0.001).
Conclusion: These results indicate that, while C activation occurs in both SMA and UM, C consumption is excessive in SMA. It is speculated that in SMA, consumption of C exceeds its regeneration.
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http://dx.doi.org/10.1186/1475-2875-8-7 | DOI Listing |
Front Immunol
November 2024
Immunochemistry Laboratory, Butantan Institute, São Paulo, Brazil.
Introduction: Complement activation split products are signatures of many immunopathological disorders. Among the laboratory findings observed in these diseases, a reduction in the level of circulating intact complement components can be mentioned, and this change has also been detected in envenomation by multiple Africanized honeybee (Apis mellifera) stings. Although envenomation by these animals elicits diverse life-threatening reactions, the capacity of bee venom (AmV) to activate the human complement system remains elusive.
View Article and Find Full Text PDFNeurol Neuroimmunol Neuroinflamm
September 2024
From the Department of Neurology (K.K., H.K., Y.M., N.S., N. Yamazaki, N. Yamamoto, S.U., C.N., H.O., Y.T., T.T., K.F., T.M., M.A.), Tohoku University Graduate School of Medicine, Sendai, Japan; Multiple Sclerosis and Neuromyelitis Optica Center (H.K., K.F.), Southern TOHOKU Research Institute for Neuroscience, Koriyama; Department of Multiple Sclerosis Therapeutics (H.K., K.F.), Fukushima Medical University, Fukushima, Japan; Department of Neurology (T.T.), NHO Yonezawa National Hospital, Yamagata, Japan; Division of Neurology (J.F., I.N.), Tohoku Medical and Pharmaceutical University, Sendai, Japan; Department of Neurology (Y.H.), Japanese Redcross Maebashi Hospital; Department of Neurology (Y.H.), Mihara Memorial Hospital, Isesaki, Japan; and Center for Brain Research (H.L.), Medical University of Vienna, Austria.
Objectives: In myelin oligodendrocyte glycoprotein IgG-associated disease (MOGAD) and aquaporin-4 IgG+ neuromyelitis optica spectrum disorder (AQP4+NMOSD), the autoantibodies are mainly composed of IgG1, and complement-dependent cytotoxicity is a primary pathomechanism in AQP4+NMOSD. We aimed to evaluate the CSF complement activation in MOGAD.
Methods: CSF-C3a, CSF-C4a, CSF-C5a, and CSF-C5b-9 levels during the acute phase before treatment in patients with MOGAD (n = 12), AQP4+NMOSD (n = 11), multiple sclerosis (MS) (n = 5), and noninflammatory neurologic disease (n = 2) were measured.
Am J Physiol Cell Physiol
February 2024
Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
Thoracic aortic aneurysm/dissection (TAAD) is a lethal vascular disease, and several pathological factors participate in aortic medial degeneration. We previously discovered that the complement C3a-C3aR axis in smooth muscle cells promotes the development of thoracic aortic dissection (TAD) through regulation of matrix metalloproteinase 2. However, discerning the specific complement pathway that is activated and elucidating how inflammation of the aortic wall is initiated remain unknown.
View Article and Find Full Text PDFClin Chim Acta
February 2024
Centre de Recherche des Cordeliers, Sorbonne Université, Inserm, Université Paris Cité, Inflammation, Complement and Cancer Team, Paris, France; Laboratory of Immunology, Georges Pompidou European Hospital, APHP, Paris, France; Paris Cité University, Paris, France. Electronic address:
Introduction: The complement system is involved in numerous diseases, through diverse mechanisms and degree of activation. With the emergence of complement targeting therapeutic, simple and accessible tools to evaluate the extent of complement activation are strongly needed.
Methods: We evaluated two multiplex panels, measuring complement activation fragments (C4a, C3a, C5a, Bb, Ba, sC5b9) and intact components or regulators (C1q, C2, C3, C4, C5, FD, FP, FH, FI).
Proteins
April 2024
Chemical Biology Laboratory, School of Basic Sciences, Indian Institute of Technology Bhubaneswar, Odisha, India.
Human complement fragment 5a (C5a) is one of the most potent glycoproteins generated downstream of C3a and C4a during late-stage activation of the complement signaling cascade. C5a recruits receptors like C5aR1 and C5aR2 and is established to play a critical role in complement-mediated inflammation. Thus, excessive C5a in the plasma due to aberrant activation of the complement contributes to the pathophysiology of several chronic inflammatory diseases.
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