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The Acute Phase Complement Proteins
Published in Andrzej Mackiewicz, Irving Kushner, Heinz Baumann, Acute Phase Proteins, 2020
Each of the human class III MHC genes — C2, Bf, C4A, and C4B — is upregulated by IFNγ, but the magnitude and kinetics of the response varies considerably. For example, the response of Bf to IFN is more rapid (<4 h) and of greater magnitude than the response of C2 (>10 h). Likewise, the response of C4A is greater and more prolonged than for C4B.93 In human monocytes, IFNγ prevents the rapid extinction of C4A or C4B expression with time in culture. Surprisingly, this effect of IFN on C4 expression in human monocytes is counterregulated by picogram concentrations of LPS. The LPS inhibitory effect on C4 is not mediated by IL-1, IL-6, or TNF.98 In contrast,71 LPS synergistically enhances the response of factor B to IFNγ.
Analyzing Complex Polygenic Traits
Published in Richard K. Burt, Alberto M. Marmont, Stem Cell Therapy for Autoimmune Disease, 2019
Bernard R. Lauwerys, Edward K. Wakeland
Historically, the most striking demonstration that gene polymorphisms might be involved in the pathogenesis of autoimmune diseases comes from the analysis of patients harboring hereditary deficiencies in complement factors Clq, C2 and C4. Thus, over 90% of patients presenting with homozygous Clq deficiency (41 cases reported to date) develop a severe lupus-like disorder characterized by malar rash, glomerulonephritis and production of antinuclear antibodies.1-3 Complete C4 deficiency is an extremely rare condition (28 cases reported) since the human genome contains about 2 to 8 copies of the C4 gene, each of them encoding a C4A or a C4B molecule according to polymorphic variations in exon 26 of the sequence. In this group of patients, the prevalence of systemic lupus erythematosus (SLE) is about 75%.4 Finally, the most common inherited complement deficiency in humans is homozygous C2 deficiency with an estimated prevalence of 1:20,000, one third of them developing a mild form of SLE.5
Host Defense I: Non-specific Immunity
Published in Constantin A. Bona, Francisco A. Bonilla, Textbook of Immunology, 2019
Constantin A. Bona, Francisco A. Bonilla
The C3a and C5a complement fragments are also called anaphylatoxins. (C4a is also an anaphylatoxin, but it is 100 and 20,000 fold less potent than C3a and C5a, respectively.) These molecules have many pro-inflammatory activities which are summarized in Table 10–V. These effects result in localized increases in vascular permeability, and contraction of smooth muscle. Additional effects are platelet aggregation, microthrombosis, blood stasis, accumulation of extravascular fluid (edema), recruitment and activation of phagocytic cells, and localized tissue destruction.
Neuroinflammation and oxidative stress in schizophrenia: are these opportunities for repurposing?
Published in Postgraduate Medicine, 2022
Zarrin Ansari, Sudhir Pawar, Rajmohan Seetharaman
The major histocompatibility (MHC) locus located on chromosome 6 has the highest association with SCZ. Incidentally, this region encodes genes that are involved with innate immunity. The complement component 4A (C4A), highly associated with SCZ, is also associated with the innate immunity system that recognizes foreign pathogens and apoptotic cells and leads them to their destruction by macrophages. This complement component also plays an important role in the various stages of brain development, including neurogenesis, cellular migration, and microglia-mediated pruning of the synapses. The above findings may suggest that the complement component may be directly implicated for its impact on SCZ pathology. Also, various genomic studies have implicated alteration of cytokines in SCZ, reflected by alteration in the regulatory functions of interferons and interleukins. All these together simply imply that SCZ and neuroinflammation have a complex genetic association and this needs to be further validated [53].
Levels of lymphocyte-associated regulators of complement system CD55 and CD59 are changed in schizophrenia patients
Published in International Journal of Psychiatry in Clinical Practice, 2021
Alper Togay, Bilge Togay, Deniz Ozbay Gediz, Sadıka Halide Akbaş, Sadi Köksoy
Genome-wide association studies on schizophrenia detected a strong association with loci in the MHC region (Ripke et al. 2014), which was confirmed by later studies with larger sample sizes (Li et al. 2017; Pardiñas et al. 2018). Further studies demonstrated that this association may be explained by the involvement of the complement system and specifically by the complement factor 4A (C4A) (Sekar et al. 2016). The classical complement cascade is important for the synaptic refinement and pruning in the developing central nervous system, and inhibition of C4 results in reduced synaptic pruning in mice (Sekar et al. 2016). Since synaptic pruning is also altered in schizophrenia (Wang et al. 2019), many studies were conducted to reveal the role of immune system genes in the disease (Li et al. 2017; Sanders et al. 2017; Pardiñas et al. 2018). In a recent study, Sager et al. (2020) reported that CD46 and CD55 were increased in the human prefrontal cortex in the first 5 years of life, suggesting that dysregulation of complement system may predispose the brain to neurodevelopmental disorders such as schizophrenia. However, the involvement of immune system in the disease aetiology and pathology is still not well understood.
Peripheral signature of altered synaptic integrity in young onset cannabis use disorder: A proteomic study of circulating extracellular vesicles
Published in The World Journal of Biological Psychiatry, 2023
Suhas Ganesh, TuKiet T. Lam, Rolando Garcia-Milian, Deepak Cyril D'Souza, Angus C. Nairn, Katya Elgert, Erez Eitan, Mohini Ranganathan
Three of the top differentially abundant proteins were validated using ELISA. CFP was measured in 8-fold dilution using ELISA kit (Thermo Scientific, Cat. EH383RB). C4A was measured in 2-fold dilution using Luminex kit (Sigma-Aldrich, Cat. HCMP2MAG-19K-07). SHANK1 was measured without any dilution using ELISA kit (MyBioSource Cat. MBS9339587). A positive correlation was noted between the MS and the ELISA concentrations for each protein—CFP (spearman rho = 0.52, p = .018), C4A (spearman rho = 0.32, p = .17), and SHANK1 (Spearman rho = 0.36, p = .12). Within the CUD sub-sample, a statistically significant correlation was noted between MS and ELISA concentrations for SHANK1 (spearman rho = 0.7, p = 0.02).