Topic: Can someone explain what C3A and C4A measure
cantgiveupyet
Frequent Contributor (1K+ posts)
Member # 8165
posted
My dr office called today and mine are very high, close to three times that of the high range.
So far i have everythng wrong with me that is listed in the mold warrior book.
does this mean it is mold? The nurse that called didnt go into too much detail.
thanks
-------------------- "Say it straight simple and with a smile."
"Thus the task is, not so much to see what no one has seen yet, But to think what nobody has thought yet, About what everybody sees."
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pos babs, bart, igenex WB igm/igg Posts: 3156 | From Lyme limbo | Registered: Oct 2005
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david1097
Frequent Contributor (1K+ posts)
Member # 3662
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i THINK c3a and c4a are non specific but are associated with chronic obstructive pulminary disease and/or Asthma.
From this I would also think that this could be mold related. Have you used one of the mold detection kits?
Posts: 1184 | From north america | Registered: Feb 2003
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lymie tony z
Frequent Contributor (1K+ posts)
Member # 5130
posted
Hey don't Panic...
cuz these tests remind me of cancer antigen tests done at labcorp...
BUT THey were C3 and C4 tests or CA3 or CA4 which could be totally different tests...
zman
-------------------- I am not a doctor...opinions expressed are from personal experiences only and should never be viewed as coming from a healthcare provider. zman Posts: 2527 | From safety harbor florida(origin Cleve., Ohio | Registered: Jan 2004
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cantgiveupyet
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Member # 8165
posted
im not panicking and all..........ive been sick way to long to panic any more. I just want to figure out how to treat this illness.
Im just trying to see what this all means and if it is lyme, mold, yeast or what.
i did some research and these tests measure inflamation, and are mentioned in mold warriors.
there is mold here in my home.....but ive lived here for 7 years and im not sure why last year things came crashing down for me health wise like they did.
thanks
-------------------- "Say it straight simple and with a smile."
"Thus the task is, not so much to see what no one has seen yet, But to think what nobody has thought yet, About what everybody sees."
-Schopenhauer
pos babs, bart, igenex WB igm/igg Posts: 3156 | From Lyme limbo | Registered: Oct 2005
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cantgiveupyet
Frequent Contributor (1K+ posts)
Member # 8165
posted
Up for anymore input.
I got my actual numbers and the C3a is over 13,000 range is 0-940
C4a is 4173 range is 0-2830
-------------------- "Say it straight simple and with a smile."
"Thus the task is, not so much to see what no one has seen yet, But to think what nobody has thought yet, About what everybody sees."
-Schopenhauer
pos babs, bart, igenex WB igm/igg Posts: 3156 | From Lyme limbo | Registered: Oct 2005
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Michelle M
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Member # 7200
posted
Sorry; I checked www.labtestsonline.org - a good source for incomprehensible test stuff ... and can't find these tests. Maybe your doc can send you a copy so you can see a longer name for the test?
Michelle
Posts: 3193 | From Northern California | Registered: Apr 2005
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cantgiveupyet
Frequent Contributor (1K+ posts)
Member # 8165
posted
the labcorp printout says C3a complement protein
-------------------- "Say it straight simple and with a smile."
"Thus the task is, not so much to see what no one has seen yet, But to think what nobody has thought yet, About what everybody sees."
-Schopenhauer
pos babs, bart, igenex WB igm/igg Posts: 3156 | From Lyme limbo | Registered: Oct 2005
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SForsgren
Frequent Contributor (1K+ posts)
Member # 7686
posted
You mentioned that you have the Mold Warriors book. Take a look there. c4a is an indicator that Dr. S suggests is indicative of hyperacute Lyme disease. It is all spelled out in the book.
-------------------- Be well, Scott Posts: 4617 | From San Jose, CA | Registered: Jul 2005
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riversinger
Frequent Contributor (1K+ posts)
Member # 4851
posted
If you have a mold or Lyme sensitive gene type, your don't react until your immune system has been triggered. The C3a and C4a are some of the indicators that the immune cascade seen in biotoxin illness has been triggered. Consistently high C4a may be related to perseistent infection of Lyme disease.
However, mold exposure will aggravate things. Dpeneding on your susceptibility type, you may not have reacted to molds until the Lyme triggered the inflammation. Once you beging being reactive, you will not get well until the mold is removed.
Here are some quotes on info on C3a and C4a. I have had levels as high as 27,500. It can be managed with the protocol in Mold warriors.
Complement components C3, C4 and C5 are large glycoproteins that have important functions in the immune response and host defence [ 1 ]. They have a wide variety of biological activities and are proteolytically activated by cleavage at a specific site, forming a- and b-fragments [ 2 ].
A-fragments form distinct structural domains of approximately 76 amino acids, coded for by a single exon within the complement protein gene. The C3a, C4a and C5a components are referred to as anaphylatoxins [ 2 , 3 ]: they cause smooth muscle contraction, histamine release from mast cells, and enhanced vascular permeability [ 3 ]; they also mediate chemotaxis, inflammation, and generation of cytotoxic oxygen radicals [ 3 ]. The proteins are highly hydrophilic, with a mainly alpha-helical structure held together by 3 disulphide bridges [ 3 ].
The complement system is a potent mechanism for initiating and amplifying inflammation. This is mediated through fragments of complement components. To the most well-defined fragments belong anaphylatoxins.
Anaphylatoxins are proteolytic products of the serine proteases of the complement system: C3a, C4a and C5a. They are polypeptides containing approximately 75 amino acid residues and meet all the criteria which characterize local hormones. The C-terminal arginine in the molecule of C3a is of fundamental importance for its biological activity.
As soon as arginine is removed, the biological activity disappears completely. In the case of C5a, the removal of C-terminal arginine (C5a ) only decreases its biological activity. The production of anaphylatoxins follows not only from complement activation, but also from activation of other enzyme system which may directly cleave C3, C4 and C5.
Such enzymes include plasmin, kallikrein, tissue and leukocyte lysosomal enzymes, and bacterial proteases.
The anaphylatoxins have powerful effects on blood vessel walls, causing contraction of smooth muscle and an increase in vascular permeability. These effects show specific tachyphylaxis (i.e. repeated stimulation induces diminishing responses) and can be blocked by antihistamines; they are probably mediated indirectly via release of histamine from mast cells and basophils.
C5a is the most powerful, approximately 100 times more effective than C3a, and 1000 times more effective than C4a. The smooth muscle contraction in the lungs is primarily mediated by LTC and LTD . This activity decrease in the following order: C5a histamine acetylcholine C3a C4a
The isolated C4a was spasmogenic for guinea pig ileum at a concentration of 1 � M and it desensitized the muscle (i.e., produced tachyphylaxis) with respect to human C3a anaphylatoxin (at 0.33 � M) but not with respect to human C5a anaphylatoxin. Increased vascular permeability was observed in human skin after intradermal injection of 1 nmol of C4a, as evidenced by immediate erythema and edema formation.
The spasmogenic, tachyphylactic, and vascular activities of C4a were abrogated by removal of the COOH-terminal arginine, a property that is characteristic also of the C3a and C5a anaphylatoxins. Contamination of C4a with either C3a or C5a has been ruled out by using radioimmunoassays for these peptides.
Although C4a is considerably less active than are C3a and C5a, the present observations suggest that C4a constitutes a heretofore unrecognized anaphylatoxin that is related biologically and chemically to the activation peptides of C3 and C5.
The fourth component of human complement (C4), an essential factor of the innate immunity, is represented as two isoforms (C4A and C4B) in the genome. Although these genes differ only in 5 nucleotides, the encoded C4A and C4B proteins are functionally different.
Based on phenotypic determination, unbalanced production of C4A and C4B is associated with several diseases, such as systemic lupus erythematosus, type 1 diabetes, several autoimmune diseases, moreover with higher morbidity and mortality of myocardial infarction and increased susceptibility for bacterial infections. Despite of this major clinical relevance, only low throughput, time and labor intensive methods have been used so far for the quantification of C4A and C4B genes.
Substitution of a Single Amino Acid (Aspartic Acid for Histidine) Converts the Functional Activity of Human Complement C4B to C4A MC Carroll, DM Fathallah, L Bergamaschini, EM Alicot and DE Isenman
The C4B isotype of the fourth component of human complement (C4) displays 3- to 4-fold greater hemolytic activity than does its other isotype C4A. This correlates with differences in their covalent binding efficiencies to erythrocytes coated with antibody and complement C1.
C4A binds to a greater extent when C1 is on IgG immune aggregates. The differences in covalent binding properties correlate only with amino acid changes between residues 1101 and 1106 (pro-C4 numbering)-namely, Pro-1101, Cys-1102, Leu-1105, and Asp-1106 in C4A and Leu-1101, Ser-1102, Ile-1105, and His-1106 in C4B, which are located in the C4d region of the chain.
To more precisely identify the residues that are important for the functional differences, C4A-C4B hybrid proteins were constructed by using recombinant DNA techniques. Comparison of these by hemolytic assay and binding to IgG aggregates showed that the single substitution of aspartic acid for histidine at position 1106 largely accounted for the change in functional activity and nature of the chemical bond formed (ester vs. amide).
Surprisingly, substitution of a neutral residue, alanine, for histidine at position 1106 resulted in an increase in binding to immune aggregates without subsequent reduction in the hemolytic activity. This result strongly suggests that position 1106 is not "catalytic" as previously proposed but interacts sterically/electrostatically with potential acceptor sites and serves to "select" binding sites on potential acceptor molecules.
The anaphylatoxins C3a, C4a and C5a, bioactive fragments of the complement components C3, C4 and C5, respectively, which have spasmogenic on smooth muscles, play a key role in mediation of immunologically provoked inflammatory responses.1,2 The biologic functions, mediated through binding to specific receptors (C3aR for C3a and C4a; C5aR for C5a), involve phagocytic cell chemotaxis and activation, stimulation of lymphokine and cytokine release, and other cell activation events.3
C4a production results from classical pathway activation; whereas, C3a and C5a are produced by activation of the terminal sequence through the classical pathway and/or the alternative pathway.4 C3a, C4a and C5a are inactivated in vivo to the less potent forms C4a desArg, C3a desArg and C5a desArg by serum carboxypeptidase N cleavage of the N-terminal arginine.3,4
C5a is rapidly cleared from the circulation by binding to neutrophil C5aR even before carboxypeptidase N inactivation,4 hence is unlikely to be a clinically useful analyte.4 C4a concentrations should probably not be used as a marker of classical pathway activation when there is confirmed or suspected renal disease because C4a is cleared by the kidneys.4,5
In general, monitoring of complement activation with C3a is preferred over C4a and C5a assays.4 Accurate measurement of C3a and/or C3a desArg is confounded by in vitro generation of C3a when blood samples are collected in EDTA tubes. Addition of the synthetic protease inhibitor FUT-175 (nafamostat mesilate [Futhan�]) to EDTA in the collection tubes minimizes spurious in vitro complement activation.4
Elevated C3a concentrations are found in most patients with active SLE; C3a concentrations start to rise 1-2 months before SLE flares (e.g., nephritis, pericarditis and/or cutaneous vasculitis), and are also elevated in pregnant SLE patients.4 C3a is elevated in 33% of patients with non- immune nephropathy (polycystic kidney, hydronephropathy).4
Elevated C3a is also reported in patients with rheumatoid arthritis, multiple sclerosis, Guillian-Barr� syndrome, diabetes, neonatal bacterial infection, sepsis, acute respiratory distress syndrome, thermal injury and following different forms of extracorporeal circulation such as hemodialysis and cardiopulmonary bypass.4
Anaphylatoxins are low-molecular weight, biologically active peptides that are defined functionally by their actions on small blood vessels, smooth muscle, mast cells, and peripheral blood leukocytes (111). Several laboratory studies have been carried out to establish, conclusively, that low-molecular-weight peptides with anaphylatoxin activity can be generated enzymatically from C3, C4, and C5 (i.e., C3a, C4a, and C5a, respectively) (112 114).
Analyses of the complete amino acid sequences of C3a, C4a, and C5a from man and from a variety of animal species have revealed striking similarities among these peptides, suggesting a common evolutionary origin. C3a was the first anaphylatoxin to have its complete primary structure elucidated (115).
C4a has a pentapeptide structure, and contracts smooth muscle, although it is approximately 500-fold less active in this respect than the C3a pentapeptide (116). C5a functions also as a chemoattractant, inducing the migration of leukocytes into an area of complement activation. These molecules induce smooth muscle contraction and enhance vascular permeability.
They bind to specific receptors and induce the release of vasoactive amines such as histamine from mast cells and basophils, and lysosomal enzyme release from granulocytes (particularly C3a and C5a) (117,118).
The activities of the anaphylatoxins, C3a and C5a, are abolished by anaphylatoxin inactivator (AI), which removes the carboxyl-terminal arginine from both molecules yielding C3a des Arg and C5a des Arg, respectively (119). The anaphylatoxin inactivator simply functions as a regulator of anaphylatoxin activity. The physical and/or the chemical properties that render human C3a and C5a so susceptible to the action of the anaphylatoxin inactivator are unknown.
In addition to stimulating effector functions of neutrophils and monocytes, human anaphylatoxins exhibit immunoregulatory activities. When added to lymphocytes and macrophages in vitro, C3a, C5a, and C5a des Arg can influence both humoral and cell mediated immune responses (120) .
Human C3a, for example, but not C3a des Arg, suppresses antigen-specific as well as polyclonal antibody responses of both mouse spleen cells and human peripheral blood leukocytes. Similar effects have been observed in experiments using synthetic peptides corresponding to the carboxyl-terminal portion of human C3a (121), and they have been attributed either to C3a-mediated generation of suppressor T-lymphocytes ( 122), or to C3a-mediated generation of a prostaglandin by mononuclear leukocytes ( 123) .
Synthetic peptides corresponding to the carboxyl-terminal portion of human C3a also have been found capable of inhibiting human T-lymphocyte migration and generation of lymphokines (124). Human C5a and C5a des Arg, on the other hand, have been found capable of augmenting antigen-specific as well as non-specific humoral immune responses of both mouse spleen cells and human peripheral blood leukocytes (125 127).
Human C5a and C5a des Arg also potentiate antigen- and alloantigen-induced human T lymphocyte proliferative responses as well as human T-lymphocyte-mediated cytotoxic reactions. Although helper T-cells are required for C5a-mediated potentiation of polyclonal antibody responses, C5a may not act directly on lymphocytes. Rather, evidence has been presented that C5a enhances humoral immune reactions in vitro by binding to macrophages and, possibly, by stimulating production of interleukin-1 (128).
Tincup
Honored Contributor (10K+ posts)
Member # 5829
posted
Good info.. but one question.. or a few actually.
If you have elevated C4a.. what do you do to lower it?
Or does it need to be lowered?
Or is it just one of those (like MSH)... "looky here we have this test showing this and that and we don't know what the heck it means or how to change it. So pay us the big bucks for the test and go live happily ever after."
And it is NOT from mold.. it would be from infections.
Other than kill infections.. what, if anything, can be done? And if you kill infections.. does it go back to normal readings?
riversinger
Frequent Contributor (1K+ posts)
Member # 4851
posted
Hi Again!
Quickly, to lower C4a, you would use treatments as necessary according to labs. Cholestyramine if other inflammatory markers show the need (high leptin, high MMP-9, low MSH), Actos for high Leptin and MMP-9, and once those are in line, sometimes Procrit is used to lower the C4a.
C3a can sometimes be lowered with a short burst of high dose statins, or with high dose fish oils. However, it is best to correct other things before directly going after either C3a or C4a, as sometimes they will self correct when the other markers come back into line.
That includes treating infections when present, and avoiding mold in your environment, so as to not trigger more inflammation.
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