Clinical trial NCT03469219: Serum Granulysin Level as a Marker to Detect the Severity of Psoriasis
Official title: Serum Granulysin as a Possible Key Marker to Detect the Severity of Psoriasis
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Psoriasis Vulgaris
Keywords: granulysin
Lead sponsor: Assiut University
Sponsor class: OTHER
First posted: 2018-03-19
Enrollment: 45
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Dermatology clinic at Assiut University.

Brief summary: Psoriasis is a chronic inflammatory and proliferative papulosquamous skin disease of unknown cause,overexpression of Anti Microbial Peptides is characteristic of psoriasis.

Granulysin is a cytolytic and proinflammatory peptide that belongs to a family of saposin-like, lipid binding antimicrobial peptides, and localized in the granular compartments of cytotoxic T lymphocytes and natural killer cells,Patients with psoriasis had high tissue granulysin expression, which increased with increased clinical severity of the disease.

The aim of the study is to measure serum granulysin level and correlate with severity of psoriasis and tissue level of granulysin.

Detailed description: The pathogenesis of psoriasis involves dynamic interactions between multiple cell types and numerous cytokines in response to triggers in genetically predisposed individuals leading to activation of T cells and their migration into skin, in addition to dysregulation of immunological cell function, keratinocyte proliferation takes place.

Psoriatic lesions are densely infiltrated by T cells and dendritic cells , the majority of T cells in the dermis are T-helper cells, while T cytotoxic cells predominate in the epidermis. T helper1 secrets cytokines, such as interferon gamma, tumor necrosis factor-alpha and interleukin 12. Recently discovered population of T helper cells called T helper17 cells which secrets interleukin 17 and interleukin 22 which stimulates epidermal proliferation, while interleukin 17 is responsible for the release of proinflammatory cytokines, antimicrobial peptides and chemokines.

A significant upregulation of perforin-expressing lymphocytes, especially cytotoxic T cells and natural killer cells, has been observed in psoriatic patients at the systemic and local levels. Perforin is a prototype granular cytotoxic mediator that ensures the quick access of pro-apoptotic molecules, such as granzymes and granulysin, into the target cells to induce apoptosis .

Granulysin is well associated with diverse activities of natural killer cells and cytotoxic T cells in physiological and pathological settings and could be a useful serum marker for monitoring host cell mediated immune cytotoxic responses.

Granulysin contributes toward the defense mechanisms against mycobacterial and viral infections as it can kill microbial pathogens through disruption of their membrane integrity, this can explain why infections is extremely rare in psoriatic lesions as psoriasis had high tissue granulysin expression, which increased with increased clinical severity of the disease.

Granulysin was found in the sera of healthy individuals at minimal concentrations.

No previous studies performed to detect the level of serum granulysin in patients with psoriasis vulgaris.

Eligibility criteria: Inclusion Criteria:

* Patients with clinically typical psoriatic lesions of different ages and sex.
* Patients with psoriasis vulgaris .
* Different degrees of severity according to Psoriasis Area and Index (PASI) Score

Exclusion Criteria:

* Pregnant and lactating women.
* Patients received systemic medical treatment in the last one month.
* Patients with associated disease reported to increase the release of granulysin whether systemic e.g(infection, cancer, organ transplantation, autoimmune disease) or skin e.g( lichen planus , steven Johnson syndrome, toxic epidermal necrolysis, viral vesicles) and patients with severe immune deficiency treated by cell therapy.

Primary outcomes:
measure: serum granulysin level
timeFrame: 1 hour
Secondary outcomes:
measure: lesional tissue granulysin level
timeFrame: 24 hours
measure: perilesional tissue granulysin level
timeFrame: 24 hours
Other outcomes:
Locations:
city: Assiut
country: Egypt
facility: Assiut University
Study officials:
affiliation: Assiut University
name: Hisham Diab, assis prof
role: STUDY_DIRECTOR
References:
citation: Elgarhy LH, Shareef MM, Moustafa SM. Granulysin expression increases with increasing clinical severity of psoriasis. Clin Exp Dermatol. 2015 Jun;40(4):361-6. doi: 10.1111/ced.12560. Epub 2015 Feb 2.
citation: Vicic M, Peternel S, Simonic E, Sotosek-Tokmadzic V, Massari D, Brajac I, Kastelan M, Prpic-Massari L. Cytotoxic T lymphocytes as a potential brake of keratinocyte proliferation in psoriasis. Med Hypotheses. 2016 Feb;87:66-8. doi: 10.1016/j.mehy.2015.12.004. Epub 2015 Dec 12.
citation: Massari D, Prpic-Massari L, Kehler T, Kastelan M, Curkovic B, Persic V, Ruzic A, Laskarin G. Analysis of granulysin-mediated cytotoxicity in peripheral blood of patients with psoriatic arthritis. Rheumatol Int. 2012 Sep;32(9):2777-84. doi: 10.1007/s00296-011-2013-9. Epub 2011 Aug 10.
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citation: Murphy M, Kerr P, Grant-Kels JM. The histopathologic spectrum of psoriasis. Clin Dermatol. 2007 Nov-Dec;25(6):524-8. doi: 10.1016/j.clindermatol.2007.08.005.
citation: Nair RP, Ding J, Duffin KC, Helms C, Voorhees JJ, Krueger GG, Bowcock AM, Abecasis GR, Elder JT. Psoriasis bench to bedside: genetics meets immunology. Arch Dermatol. 2009 Apr;145(4):462-4. doi: 10.1001/archdermatol.2009.73. No abstract available.
citation: Ogawa K, Takamori Y, Suzuki K, Nagasawa M, Takano S, Kasahara Y, Nakamura Y, Kondo S, Sugamura K, Nakamura M, Nagata K. Granulysin in human serum as a marker of cell-mediated immunity. Eur J Immunol. 2003 Jul;33(7):1925-33. doi: 10.1002/eji.200323977.