Complement haemolytic activity, circulating immune complexes and the morbidity of sickle cell anaemia

Anyaegbu, Chidozie C.; Okpala, Iheanyi; Akenova, A.; Ls, Salimonu

doi:10.1111/j.1699-0463.1999.tb01463.x

Cited by 26 publications

(11 citation statements)

References 17 publications

(10 reference statements)

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“…Therefore, for functional assays of MPs, AX or other surface markerbased affinity isolation is highly recommended. 46,47 Our findings also have relevance to nonrheumatologic diseases, such as acute coronary syndrome and sickle cell disease in which the presence of circulating ICs is well documented 48,49 and may cause interference with MP detection.…”

Section: Microparticles and Protein Complexes E45mentioning

confidence: 63%

Detection and isolation of cell-derived microparticles are compromised by protein complexes resulting from shared biophysical parameters

György

Módos

Pállinger

et al. 2011

Blood

380

410

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Numerous diseases, recently reported to associate with elevated microvesicle/ microparticle (MP) counts, have also long been known to be characterized by accelerated immune complex (IC) formation. The goal of this study was to investigate the potential overlap between parameters of protein complexes (eg, ICs or avidinbiotin complexes) and MPs, which might perturb detection and/or isolation of MPs. In this work, after comprehensive characterization of MPs by electron microscopy, atomic force microscopy, dynamic lightscattering analysis, and flow cytometry, for the first time, we drive attention to the fact that protein complexes, especially insoluble ICs, overlap in biophysical properties (size, light scattering, and sedimentation) with MPs. This, in turn, affects MP quantification by flow cytometry and purification by differential centrifugation, especially in diseases in which IC formation is common, including not only autoimmune diseases, but also hematologic disorders, infections, and cancer. These data may necessitate reevaluation of certain published data on patient-derived MPs and contribute to correct the clinical laboratory assessment of the presence and biologic functions of MPs in health and disease. (Blood. 2011;117(4):e39-e48) IntroductionMembrane vesicles are small subcellular structures surrounded by a phospholipid bilayer. Their release by various cell types is enhanced during activation and apoptosis. 1 They represent heterogeneous structures and can be classified into several groups depending on their size, antigenic features, and mechanism of cellular release. 1 The two best characterized categories include exosomes and microvesicles/microparticles (MPs). Both populations are characterized by the exposure of phosphatidylserine, which allows annexin-V (AX) to bind to these-lipid surfaces. 1 Exosomes are composed of small, 50-to 100-nm-sized structures released on exocytosis of multivesicular bodies. 1 The diameter of MPs, formed by membrane blebbing, is described to be 100 to 1000 nm 2 . However, precise definitions of MPs are still lacking. 1,2 MPs are found in various biologic fluids, including blood plasma, 3 urine, 4 and synovial fluid (SF). 5,6 Numerous flow cytometry (FC) studies using blood plasma have shown correlation of MP counts with human cardiovascular 7 and autoimmune diseases, 8 hematologic disorders, 9 and cancer. 10 Of particular interest, autoimmune diseases were reported to be characterized by elevated levels of MPs. 11 The assessment of exosomes and MPs is complicated by the presence of further known categories of membrane bound subcellular structures, such as apoptotic vesicles, exosome-like vesicles, membrane particles, and ectosomes. 1 There is a substantial size overlap among the aforementioned vesicle categories, and the size distribution of a given vesicle preparation may also be affected by the method used for their isolation. 3,12,13 Recently, attempts have been made to standardize isolation and detection protocols for membrane vesicles. 3,14 Up until now, no systemat...

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Section: Microparticles and Protein Complexes E45mentioning

confidence: 63%

Detection and isolation of cell-derived microparticles are compromised by protein complexes resulting from shared biophysical parameters

György

Módos

Pállinger

et al. 2011

Blood

380

410

View full text Add to dashboard Cite

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“…Hydroxyurea, which has undergone large clinical trials in SCD, confers benefit partly by inhibiting leukocyte adhesive interactions [17 ,26,27]. It is also immunosuppressive, which calls for further caution in SCD patients who are already immunocompromised and susceptible to infections [39]. It is also immunosuppressive, which calls for further caution in SCD patients who are already immunocompromised and susceptible to infections [39].…”

Section: Resultsmentioning

confidence: 99%

Leukocyte adhesion and the pathophysiology of sickle cell disease

Okpala

2006

Current Opinion in Hematology

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“…However, the increased neutrophils are mostly dysfunctional due to impaired chemotaxis, migration, and killing ability . Impairment of the alternate pathway of complement activation through qualitative and quantitative deficiencies of factors B and C3 has also been reported , although this observation has not been consistent between studies .…”

Section: Innate Immune Dysfunction In Scamentioning

confidence: 98%

Alteration of lymphocyte phenotype and function in sickle cell anemia: Implications for vaccine responses

et al. 2016

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Individuals with sickle cell anemia (SCA) have increased susceptibility to infections, secondary to impairment of immune function. Besides the described dysfunction in innate immunity, including impaired opsonization and phagocytosis of bacteria, evidence of dysfunction of T and B lymphocytes in SCA has also been reported. This includes reduction in the proportion of circulating CD4+ and CD8+ T cells, reduction of CD4+ helper : CD8+ suppressor T cell ratio, aberrant activation and dysfunction of regulatory T cells (Treg), skewing of CD4+ T cells towards Th2 response and loss of IgM-secreting CD27+IgMhighIgDlow memory B cells. These changes occur on the background of immune activation characterized by predominance of memory CD4+ T cell phenotypes, increased Th17 signaling and elevated levels of C-reactive protein and pro-inflammatory cytokines IL-6 and TNF-α, which may affect the immunogenicity and protective efficacy of vaccines available to prevent infections in SCA. Thus, in order to optimize the use of vaccines in SCA, a thorough understanding of T and B lymphocyte functions and vaccine reactivity among individuals with SCA is needed. Studies should be encouraged of different SCA populations, including sub-Saharan Africa where the burden of SCA is highest. This article summarizes our current understanding of lymphocyte biology in SCA, and highlights areas that warrant future research.

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Complement haemolytic activity, circulating immune complexes and the morbidity of sickle cell anaemia

Cited by 26 publications

References 17 publications

Detection and isolation of cell-derived microparticles are compromised by protein complexes resulting from shared biophysical parameters

Detection and isolation of cell-derived microparticles are compromised by protein complexes resulting from shared biophysical parameters

Leukocyte adhesion and the pathophysiology of sickle cell disease

Alteration of lymphocyte phenotype and function in sickle cell anemia: Implications for vaccine responses

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