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BRIEF RESUME OF THE INTENDED WORK:

6.1 NEED FOR THE STUDY:

Psoriasis is a chronic, immune mediated, inflammatory disease that is driven by the IL-23/IL-17 immunologic pathway which plays an important role in the disease pathogenesis.¹

Data from clinical studies indicate that IL-17A plays a critical role in this pathway and is the most biologically active out of all cytokines ²

The IL-17 family consists of five other members besides IL-17A (IL-17B-F) . There is upregulation of these cytokines in Psoriasis. Within this fami1y,IL-17A, IL-17C, and IL-17F are implicated in psoriasis pathogenesis as their expression is increased up to eightfold in psoriatic lesions. These cytokines act on keratinocytes leading to hyper-proliferation as well as abnormal differentiation of epidermal keratinocytes. They also act on neutrophils, endothelial cells, osteoclasts, chondrocytes and osteoblasts and initiate the inflammatory pathway in these cells ultimately resulting in development of erythematous, scaly plaques and bone re-modelling³

Previous studies have shown that the levels of these cytokines, especially IL-17A are more in the psoriatic lesions than in the circulation, implying a more critical role of local cytokines than circulating ones in the development of skin damage.

Moreover, IL-17A has synergistic action with other cytokines, such as TNF-e. This gives the rational use of for treatments having dual inhibition of IL-17A and TNF-o (or other cytokines) in psoriasis patients resistant to single biologics[⁴

Various monoclonal antibodies like Secukinumab are under development to act as a potential therapeutic approach to disrupt this psoriatic inflammatory loop by inhibiting IL-17A.⁵ These biologics dramatically improve skin and joint symptoms in patients with moderate-to-severe psoriasis and psoriatic arthritis and have shown promising results.⁵

A more better understanding of immunopathogenesis of psoriasis will pave way for treatment which is based on specific immunopathogenic targets. Complex interplay of psoriasis with associated comorbidities is also a future area of research for overall better patient management and to improve their  quality of            life ⁶

It is already established that the serum levels of IL-17A are increased in psoriasis. but There are very few studies about the levels on IL-17A in scales shed from psoriatic plaques. There is also very limited data in the literature about difference in the levels of this cytokine in various clinical disease               subtypes⁷

6.1 REVIEW OF LITERATURE:

In a study by Anna Michalak-Stoma et a1, Serum IL-17 concentrations in psoriatic patients were higher than in the control group but no statistically significant difference was found. The higher level of IL-17 was detected in scale from psoriatic plaques compared to IL-17 serum level. A significant positive correlation between the IL-17 serum concentrations and psoriasis severity measured by the PASI, BSA, and PGA was found.¹

H. Takahashi et a1, observed that serum levels of IL17A was increased in patients with psoriasis which correlated with PASI and decreased after treatment suggesting that these parameters are useful in monitoring the disease activity.⁵

A study done by Yilmaz SB et all included 70 patients with psoriasis and 50 controls. IL-17 levels in serum and in skin obtained from lesions and non- lesional skin area were analyzed. Results showed that levels of serum IL-17 did not show much difference between patients and controls except in case of pustular psoriasis where significantly higher levels were found and in case of severe plaque psoriasis with PASI score >10. Lesional skin samples of psoriasis patients showed significantly higher levels of IL-17 compared with perilesional skin samples.⁷

A study by Li Ji et a1 was done to investigate the role of IL-17, IL-23 and IL-6 cytokines in lesions and non-lesional skin of the patients with psoriasis and skin tissues of normal subjects. The results showed that the levels in non lesional skin of patients were significantly lower than those of lesional skin, but higher than those in skin tissues of normal subjects. It was suggested that over expression of these cytokines in the skin lesions of patients with psoriasis may play an important role in the immunopathogenesis of psoriasis.⁸

A study by Lowes MA was done to look for T cells producing IL-17 in the dermis of psoriasis lesions. Peripheral blood, biopsy from lesions and pert-lesional skin was obtained. Results showed T cells producing IL-17 in the dermis of psoriasis lesions which increased with disease severity and normalized with cyclosporine therapy.⁹

6.2 AIMS OF THE STUDY

Correlate serum and plaque scale IL-17A levels with each other and with the severity of psoriasis

6.3 OBJECTIVES OF THE STUDY

1.        Estimation of IL-17A Serum concentrations in patients diagnosed with chronic plaque psoriasis.

2.     Estimation of IL-17A scale concentrations in patients diagnosed with chronic plaque psoriasis.

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MATERIALS AND METHODS:

7.1 SOURCE OF DATA:

A total of 79 patients attending the outpatient department of Dermatology at a Tertiary Care Hospital, Mangalore with a clinical diagnosis of psoriasis, satisfying the inclusion and exclusion criteria during an 18 month period will be included in this study.

Demographic data, medical history, physical examination, samples of serum and of scales from psoriatic plaques for assessment of IL17A will be taken from each patient included in the study.They will be  examined for extent and severity of lesions with the help of PASI scoring.

7.2 SAMPLE SIZE ESTIMATION:

Method of sampling: Purposive Sampling

Calculation of sample size: From the study done by Michalak-Stoma A et al. n = 2 [(Zα + Z_β)/C]2 + 3

C = 0.5 * 1n[(1+r)/(1-r)] = 0.4784

r = 0.610, from the Reference study

Zα = 1.96 at 95% Confidence interval

Z_β = 1.281 at 90% power

Therefore n = 79

7.3 STUDY DESIGN:

A Prospective Observational Cross Sectional Study

7.4 METHOD OF COLLECTION OF DATA

      SELECTION CRITERIA:

Inclusion criteria

1.        All patients with a clinical diagnosis of psoriasis. 2)Presence of active psoriatic skin lesions with scales

2.     Age above 18 years

Exclusion criteria:

Patients who received any systemic treatment like Methotrexate, Cyclosporine, Apremilast and                b        iologicals for psoriasis in recent 1 month

Methodology

The study will be conducted over a period of 18 months after obtaining approval from the institutional Scientific and Ethics committee.

Patients of age greater than 18years meeting the inclusion criteria will be explained about the nature of the study and a written informed consent will be obtained from each person willing to take part in the study. A patient information sheet furnished with details will be handed over to the subjects.

A detailed history and physical examination will be done for the patients included in the study.

The           patients will also be examined for the extent and severity of lesions , which will be assesed with the psoriasis area and severity score (PASI)

The range of absolute PASI scores is 0-72, with higher scores indicating a greater severity of psoriasis. A score of 0 indicates no psoriasis, while a score higher than 10 suggests severe psoriasis

Under aseptic precautions venous blood samples and scales from psoriatic plaques will be collected.

These samples will be kept in Phosphate buffered saline (1 :10) then homogenized and the levels of IL-17A will be analyzed using commercially available Enzyme Linked Immunosorbent Assay (ELISA) kits. 

DATA ANALYSIS

Data will be analyzed using standard statistical methods.

Frequency, Percentage, Mean, Standard Deviation,‘t’ test ,Chi-Square test, Kar1 Pearson coefficient of correlation and ROC analysis will be used to analyze the data.

IMPLICATIONS OF THE STUDY

This study will help us understand if there is any correlation between levels of IL-17A in serum and scales with psoriasis and if it can be used as a biomarker for disease activity which will help in diagnosis            and management of the disease.

Mean PASI correlates in patients with chronic moderate-to-severe psoriasis. A reduction in PASI of at least 75% is observed which can lead to significant improvement in quality of life in patients receiving biologicals against IL17A⁹

7.5 Does the study require any investigations or interventions to be conducted on patients? If so please describe briefly.

Yes. Venous blood samples and scales from psoriatic plaques.

7.6 Has ethical clearance been obtained from your institution in case of 7.5?

        Yes

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LIST OF REFERENCES:

1.     Michalak-Stoma A,BartosiÅ„ska J,Kowa1 M,Raczkiewicz D,Krasowska D,Chodorowska G.IL-17A in the Psoriatic Patients’ Serum and Plaque Scales as Potential Marker of the Diseases Severity and Obesity Mediators of Inf1ammation.J Hindawi.2020;1-9.

2.     Mattei PL,Corey KC,Kimball AB.Psoriasis Area Severity Index (PASI) and the Dermatology Life Quality Index (DLQI) the correlation between disease severity and psychological burden in patients treated with biological therapies.J Eur Acad Dermatol Venereol.2013;28:333-7.

3.     Blauvelt A,Chiricozzi A.The Immunologic Role of IL-17 in Psoriasis and Psoriatic Arthritis Pathogenesis.Clin Rev Allergy Immunol.2018;55:379—90.

4.     Hong D,Liu X,Qiu X,Lu S,Jiang Y,Tan G et al.Profiling Serum Cytokines and Anticytokine Antibodies in Psoriasis Patients.J Immunol Res.2022;1-9.

5.     Takahashi H,Tsuji H,Hashimoto Y,Ishida-Yamamoto A,Iizuka H.Serum Cytokines and Growth Factor Levels in Japanese Patients with Psoriasis.C1in. Exp. Dermatol.2009;35:645—9.

6.     Chhabra S,Dogra S,Sharma K,Raychaudhuri SK,Raychaudhuri SP.Recent Update on Immunopathogenesis of Psoriasis.Indian I Dermatol.2022;67:360-73

7.     Yilmaz SB,Cicek N,Coskun M,Yegin O,A1psoy E.Serum and Tissue Levels of IL-17 in Different Clinical Subtypes of Psoriasis.Arch Dermatol Res.2012;304:465-9.

8.     Li J,Chen X,Liu Z,Yue Q,Liu H.Expression of Th17 Cytokines in Skin Lesions of Patients with Psoriasis.J. Huazhong Univ. Sci. Technol. Med. Sci. J HUAZHONG U SCI-MED.2007;27:330-2.

9.     Lowes MA,Kikuchi T,Fuentes-Duculan J,Cardinale I,Zaba LC,Haider AS et a1.Psoriasis Vulgaris Lesions Contain Discrete Populations of Th1 and Th17 T Cells.J Invest Dermatol.2008;128:1207-1.