C4 complement

A significant decrease in the number of CD4+ cells as well as C3 and C4 complement levels among lead-exposed workers (n=25) relative to unexposed controls (n=25) was also reported by Undeger et al. 

Fig. 14.3 Tumor necrosis factor (TNF) locus with some of the polymorphic sites known within the TNF locus. C2, C4, complement C2, C4 Ch, chromosome HLA, human leukocyte antigen HSP, heat shock protein LTA, lymphotoxin A LTB, lymphotoxin B MHC, major histocompatibility complex. (Reproduced from ref 74 by permission of Future Medicine Ltd.)...

C4 complement. C4 complement (along with C3) provides an assessment in CSF, becoming one of the acute-phase proteins, as a prognostic marker of inflammatory disorders. 

In patients with lymphocytic CSF cytological syndromes, elevation of CSF C4 concentrations was observed. Leakage of several proteins across the blood-CSF barrier was also found. Leakage of C4 complement into CSF depends on the functional state of the barrier to a certain extent, being partially selective. Under pathological circumstances, the rate of penetration of protein fractions across the blood-CSF barrier can be modified selectively, which has been proved in CSF acute-phase reactants. They are highly influenced by the production of cytokines. These considerations evoke the question as to whether similar mechanisms of penetration can be expected in cytokines. Elucidation of the pharmacokinetics of interferons in CSF could substantially influence our approach not only to MS patients but to others as well (A18). 

A18. Adam, R, Nekola, R, Havrdova, E., Preiningerova, J., et al.. Evaluation of C4 complement in cerebrospinal fluid in inflammatory and demyeUnating diseases of CNS. Clin. Biochem. Metab. 

A 46-year-old woman, who took clonidine 25 mg bd for menopausal flushing, developed depigmentation and swelling of her forearms (25). A skin biopsy showed a pattern consistent with immune complex disease, with IgG, IgM, Clq, C2c, and C4 complement between muscle fibers and at the dermo-epidermal junctions. All of these abnormalities disappeared after withdrawal. 

Sepehri, H., Roghani, M. and Houdebine, M.L. 1998. Oral administration of pectin-rich plant extract enhances C3 and C4 complement concentration in woman colostrums. Reprod. Nutr. Dev., 38(3) 225-260. 

Turkish lead battery workers (N = 25, control N = 25) PbB elevated, >40 g/dl Serum IgG, IgM, C3, C4 complement Significant reduction in these markers (p<0.05) with increased PbB Undeger etal. (1996)... 

Several studies in Turkish lead battery workers (Ba aran and Undeger, 2000 Undeger et al., 1996) indicated Pb effects on inunune function in workers with a mean PbB of 75 p.g/dl. Significant reductions were observed in serum levels of IgG, IgM, and C3, C4 complement. It should be noted that intensity of Pb exposure was generally greater than in other worker study groups and may account for more adverse humoral immunotoxic responses. The mean PbB levels in the reports of Heo et al. (2004) and Pinkerton et al. (1998) were 22 and 39 pg/dl, respectively. Ayatollahi (2002) reported that Iranian workers with diverse forms of Pb exposures such as battery workers, car painters, and printers had reduced serum Ig levels, particularly IgG. 

The first component of complement is Cl. This is a complex of three molecules designated Clq, Clr and Cls. The classical pathway is only initiated by an immune complex (antibody bound to antigen) when Clq binds to the Fc portion of the complexed antibody (IgM or IgG). The binding of Clq activates the Clr and Cls molecules associated with it to yield activated Cl which now cleaves C4 and then C2 (subunits of... 

C4BP C4 binding protein plasma protein which acts as co-factor to factor I inactivate C3 convertase C5a Complement fragment 5a (anaphylatoxin)... 

The classical pathway can become activated by immune complexes, bacteria, viruses, and F-XIIa. Binding occurs to the complement C1 q, a part of complement factor 1 (Cl). This initiates a cascade of activations, first of Clr, Cls, then of C4. This C4 activates C2, after which C3 becomes activated. Activated C3 initiates a cascade of activations, which are in common with the alternative pathway and which end up in activated C5-9, a membrane attack complex that lyses the target. 

CH50 determinations can be used to analyze the total serum complement and are useful for monitoring immune complex diseases (Sullivan, 1989) activation of complement (Table 15.13) in the presence of autoantibodies is indicative of immune complex diseases and autoimmunity. The various components of the complement system (C3, C4) can also be measured to assess the integrity of the system. For instance, low serum concentrations of C3 and C4, with a concomitant decrease in CH50 may indicate activation of complement, while a low C4 alone is a sensitive indicator of reduced activation of the complement system. Since C3 is used as an alternate complement pathway, it usually measures high. Therefore, a low C3 with a normal C4 may indicate an alternate pathway of activation. 

Figure 1.15. Complement activation via the alternative pathway. Always present in serum are trace amounts of C3b, which may attach to recognition sites on, for example, yeast cell walls. C3b may combine with serum factor B to form C3bB, and this complex is acted upon by factor D to form C3bBb. This latter complex is a C3 convertase and may act upon C3 to form more C3b to amplify the process. The C3bBb-coated particles may activate other complement components (C4-C9) or be recognised by complement receptors on neutrophils.

Pi globulins Transferrin Haemopexin P-lipoprotein (apoB) Complement C4... 

Factors Cl to C4 (for complement ) belong to the classic pathway, while factors B and D form the reactive components of the alternative pathway. Factors C5 to C9 are responsible for membrane attack. Other components not shown here regulate the system. 

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