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Potential Biomarker in Severity, predictive and prognostic bio-marker of Atopic Dermatitis

06 Apr 2023

Background of disease :
Atopic dermatitis (AD) is a condition that causes dry, itchy and inflamed skin. It's common in young children but can occur at any age. Atopic dermatitis is long lasting (chronic) and tends to flare sometimes. It can be irritating but it's not contagious.

The need:
Atopic Dermatitis can be treated according to "one-size-fits-all" approach, which could affect the efficacy of the treatment provided.
AD diagnosis is based on clinical criteria like SCORAD, EASI and IGA which are observers subjective assessments. Hence there was a need for identification of reliable biomarkers that could reduce observatory differences and would be useful objective parameters for the diagnosis, disease severity measurement and especially for the development of precision medicine.

Advantages of TARC/CCL17 as a biomarker for Atopic dermatitis:

• Th2 and Th22 immune pathways are predominantly involved in the AD inflammatory response. CCL17/TARC is a CC chemokine and a member of the Th2 chemokine family and are involved in the recruitment of T cells in to the skin.


• CCL17/TARC levels are elevated in the serum levels in an AD patients as well as in an AD leisonal skin, this are expressed on the keratinocytes in the epidermis.


• A high correlation between serum CCL17/TARC and AD has been confirmed in paediatric patients as a biomarker.


• Increased levels of CCL17/TARC levels from the umbilical cord could also predict AD in infancy.


• High levels of CCL17/TARC may suggest frequent AD relapses even after clinical resolution.

New Updates on CCL17/TARC as a biomarker:

• In Barrier Dysfunction in Atopic new-borns study (BABY Study), the researchers used tape strips to painlessly and non-invasively to collect skin cells. They identified high levels of TARC on the skin which was associated with high risk of developing AD.


• Another study conducted by Ana B Pavel et al., identified the decrease in epidermal barrier markers like CCL14/TARC after the treatment of Oral JAK/SYK inhibition.


• Similarly a study conducted by Saakshi Khattri et al., observed that the use of Cyclosporine in AD patients significantly reduced the epidermal barrier markers.


• Although the reports on the correlations between CCL17/TARC levels in the skin and clinical severity is sparse, there is a potential to utilise these non-invasive procedures for the same.

Use of CCL17/TARC as a Diagnostic and Prognostic Marker in Various Diseases:

Diagnostic accuracy of CCL17/TARC

• In Japan, measuring CCL17/TARC as a biomarker for the efficacy and successful treatment in AD is widely used. Measuring of the same comes under the health insurance support since 2008.


• Although, CCL17/TARC is a proven to be a useful biomarker in AD, there is a huge difference in the levels among AD patients due to the complex and multiple pathology as well as the heterogenicity of the disease.


• Some patients with severe AD and patients with nodular prurigo or long standing severe chronic linchenified lesions occasionally show normal or even low CCL17/TARC levels.


• There are studies suggesting that a single biomarker cannot be a definitive for AD. Instead, presence of different biomarkers like PARC/CCL18,IL-22 and soluble IL-2 could help in better correlation on the disease severity.


• AD biomarkers including CCL17/TARC are normally detected only in moderate - severe conditions and not mild. Hence this could also be a limitation in the early diagnosis.

Conclusion

• CCL17/TARC is a one of the potential biomarkers which could be used as a predictive, diagnostic and prognostic biomarker in AD in moderate to severe condition.


• Serum CCL17/TARC levels are elevated in AD patients and this is detected through invasive procedures. However, recently in the BABY Study, using non-invasive procedures like strip tapes to collect the skin cells can help in detecting the CCL17/TARC levels, although more studies and evidence is required.


• Due to the multi-complex pathology and heterogenicity of the disease, use of a single biomarker for diagnosis of AD is not appropriate. Along with CCL17/TARC other biomarkers like PARC/CCL18,IL-22 and soluble IL-2 could help in better correlation on the disease severity.


• Identifying potential biomarkers for AD is essential to reduce the bias in observers subjective assessment, improve compliance and treatment outcome.