Since there is skepticism that exposure to mold in water-damaged buildings can cause illness, objective lab measurements are essential for proving the presence of illness. One of the main reasons I became a specialist in Chronic Inflammatory Response Syndrome, a “controversial diagnosis,” is because I recognized that I was on solid scientific footing with objective bio-markers.
If you understand that Chronic Inflammatory Response Syndrome is, first and foremost, an inflammatory disorder, then the pattern of lab abnormalities will make sense. The inhalation of mold and other inflammatory compounds within a water-damaged building causes activation of the innate immune system, a particular type of inflammatory pathway that reacts to immediate threats to the body.
There are four main inflammatory biomarkers used in the diagnosis of Chronic Inflammatory Response Syndrome. They are complement 4a (C4a), complement 3a (C3a), transforming growth factor beta-1 (TGFB-1), and matrix metallo-proteinase 9 (MMP-9). Typically, at least one of these inflammatory markers will be excessively high in a Chronic Inflammatory Response Syndrome patient. In many patients, three of them are too high–C4A, TGFB-1, and MMP-9.
C4a is part of one branch of the innate immune system called the complement pathway. The complement pathway assists the immune system in helping destroy foreign invaders including mold, bacteria, and parasites. Exposure to a water-damaged building by a genetically susceptible individual will cause C4a to sky-rocket. Once activated, the production of C4a can become self-reinforcing, a process known as auto-activation. What this means is a patient who has been exposed to a water-damaged building can have continually high levels of C4a even after he gets into a clear-air environment because of the process of auto-activation.
Like C4a, C3a is a part of the complement pathway. Unlike C4a, C3a is more specific for bacterial infections such as Lyme disease, a tick-borne illness that can cause the host to become infected by the bacteria Borrelia. To give an example, a patient with Chronic Inflammatory Response Syndrome from exposure to water-damaged buildings will have C4a increased and C3a at low or normal levels. By contrast, a patient with Chronic Inflammatory Response Syndrome from a tick-bite will have both elevated C4a and C3a. Since mold and Lyme patients are often indistinguishable based on symptoms and physical exam, C3a is a helpful additional clue about whether there is Lyme involvement.
Transforming growth factor beta-1 is another inflammatory marker. It is a complex protein that has the ability to both increase inflammation or decrease inflammation depending on the body’s condition. Furthermore, transforming growth-factor beta-1 helps cells mature and change into other cell types which is how it gets its name “transforming growth factor.” Transforming growth factor beta-1 will increase if a patient develops Chronic Inflammatory Response Syndrome from mold-exposure or a tick-bite, making it a fairly non-specific inflammatory markers, like C4a.
The final inflammatory marker that is commonly used is called matrix metalloproteinase-9 (MMP-9). MMP-9 is an enzyme that helps maintain the balance between tissue formation and breakdown. Specifically, MMP-9 is involved in the breakdown of the structural material around cells called the extracellular matrix. This function is important in normal health such as embryo development during pregnancy, reproduction, and tissue remodeling. In excess then, you can imagine that MMP-9 can cause excess break-down and damage.
Here is a summary of these labs:
Lab Abnormality Possible Significance Lab
- C4a >2,830ng/mL Mold or Lyme National Jewish
- C3a >780ng/mL Lyme National Jewish
- TGB-1 >2,380pg/mL Mold or Lyme Cambridge Biomedical
- MMP-9 >332ng/mL Mold or Lyme Labcorp