Introduction
A biomarker is generally anything that helps to know and understand any normal, physiological, pathological, or disease progression in a human body. This is especially used to identify diseases because the pathogenic process can be known once biomarkers are established. A disease can be easily diagnosed and treated when the entire pathogenic or biological process is known. Thus, biomarkers greatly help identify diseases in the human body. Such biomarkers can also be used to detect vasculitis.
What Is Vasculitis?
As the name suggests, vasculitis is a group of conditions that damage the blood vessels in the circulating system of the human body. This damage manifests as inflammation or swelling. The inflammation causes the blood vessels to thicken and obstruct blood flow to important internal organs. When such inflammation occurs in the blood vessels, the body’s immune system tries to respond by narrowing or obstructing the blood vessels.
When the cause of such inflammation cannot be elicited, the vasculitis is considered primary. If swelling of blood vessels occurs due to any underlying causative factors like infections or drugs, it is said to be secondary vasculitis. In the long term, these inflamed and thickened blood vessels can hinder the blood supply and lead to a hypoxic state of the vital organs. This can result in organ dysfunction or failure.
Why Is a Biomarker Important for Vasculitis?
- As already mentioned, vasculitis comprises a group of disorders. After identifying the thickened blood vessels, it is important to identify the type of vasculitis disorder. For every type of vasculitis, different kinds of biomarkers are available. Thus, diagnosis becomes easy and precise.
- After diagnosis, biomarkers can help in understanding the progression of vasculitis disorder. This also helps judge the kind of treatment or therapy necessary for the vasculitic disorder.
- Thus, biomarkers can help provide insight into the prognosis of the condition for a particular affected individual.
What Are the Biomarkers for Vasculitis?
Biomarkers can be available in human samples like urine and blood, molecular tissues, or radiographic specimens. Some commonly employed biomarkers for vasculitis disorders are:
- For any kind of vasculitis, acute phase reactants or proteins like C-reactive protein or erythrocyte sedimentation rate (ESR) are elevated.
- Anti-neutrophil cytoplasmic antibodies (ANCA) are proteins or IgG antibodies secreted against the neutrophils and monocytes. Such antibodies are elevated in granulomatosis with polyangiitis disorder. Specifically, the antibody produced is proteinase 3-ANCA. Recently, other biomarkers like matrix metalloproteinase (MMP-3), tissue inhibitor of metalloproteinase (TIMP-1), and chemokine ligands (CXCL13) are emerging as accurate biomarkers for granulomatosis with polyangiitis.
- Similarly, antibodies are produced against the basement membrane of the blood vessels in conditions like anti-glomerular basement membrane disease.
- In a disease like giant cell arteritis, it is important to do a radiographic investigation like an MRI (magnetic resonance imaging) to detect the condition. Recently, a biomarker called Pentraxin 3 is used to identify the level of arterial damage. Such a biomarker is structurally similar to the C-reactive protein and helps diagnose better. Other biomarkers used to confirm the diagnosis of giant cell arteritis are SGTB and FCGR3A.
- In eosinophilic granulomatosis with polyangiitis, an increased amount of circulating eosinophils is the classical feature. A recent biomarker used to differentiate eosinophilia due to other causes and vasculitis is eotaxin-3. Sometimes, ANCA can be positive in this condition with a greater predilection for perinuclear ANCA.
- Cryoglobulinemic vasculitis shows increased levels of C4 complement and cryoglobulins in the blood.
- In severe cases of Kawasaki disease, there may be cardiac involvement that manifests as myocarditis. A N-terminal pro-b-type natriuretic peptide is used to determine cardiac involvement and inflammation.
- A genetic marker, HLA-B51, is said to increase in individuals prone to developing Behcet's disease. An elevated count of this biomarker makes the patient susceptible to Behcet’s disease.
- A biopsy specimen can also be used as a biomarker. A biopsy of the brain parenchyma is taken and studied for primary angiitis of the central nervous system. Similarly, cerebrospinal fluid helps in diagnosis. Increased CD4 T cells in the cerebrospinal fluid with increased IL-17 (interleukin-17) and plasma cells indicate primary angiitis of the central nervous system.
- Takayasu’s arteritis can be diagnosed with increased biomarker levels of anti-ferritin antibodies. Increased interleukins 8 and 18 can help in confirming the diagnosis.
Other than these chemical biomarkers, radiographic images, and studies also act as biomarkers to diagnose certain diseases. Imaging modalities like angiography and MRI are techniques used to identify any defect in the blood vessel. This can indicate the presence of inflammation in a vasculitis disorder.
What Are the Challenges in Using Biomarkers for Vasculitis?
- There can be a major overlap with diagnosing other conditions because biomarkers used to diagnose vasculitis can also increase in other conditions. This is especially true in acute phase reactants, which tend to increase with vasculitic or non-vasculitic origin.
- No single marker can be used universally for a particular disease in question. This questions the credibility and accuracy of a biomarker in diagnosing a specific vasculitic condition.
- Sometimes, the levels of biomarkers can vary significantly for the same individual. Thus, the reliability of a biomarker is jeopardized.
- Biomarker levels might not always correlate with disease activity or severity, limiting their ability to reflect vasculitis's dynamic nature and progression.
- Interpretation of the results of a biomarker always requires clinical examination for accurate diagnosis. Thus, the presence of biomarkers alone does not indicate a vasculitis disorder. It has to correlate with the clinical signs and symptoms of the patient.
- The assay techniques employed and the results tabulated still require a lot of study as they need more validation. So, biomarkers alone cannot be used in the case of vasculitis.
- Extensive research is required to quantify and standardize the levels of biomarkers for a particular vasculitic disorder. Future research should be focussed on improving the sensitivity and specificity of a biomarker for a particular vasculitic condition.
Conclusion
Biomarkers are vital for every disease as they help identify, diagnose, understand the disease progress, and interpret the results for treatment planning. Such invaluable tools require continuous advancements that help in precise and easier diagnosis of a vasculitic condition. This helps monitor and manage a vasculitis condition at its best.
