Granulysin expression increases with increasing clinical severity of psoriasis

Elgarhy, Lamia Hamouda; Shareef, Mohamed; Moustafa, Sara

doi:10.1111/ced.12560

Cited by 8 publications

(8 citation statements)

References 21 publications

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“…GNLY + T cells are mainly found in the papillary dermis of psoriatic plaques and their number increases with increasing clinical severity of disease (9,10). Herein, for the first time, we demonstrated that CD8 + T lympho cytes and NK cells expressing GNLY molecule were several times more frequent in psoriasis skin, especially in epidermis compared to nonlesional and healthy skin.…”

Section: Discussionmentioning

confidence: 65%

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Systemic and Local Increase of Granulysin Expression in Cytotoxic Lymphocytes in Severe Psoriasis

Vičić

Kaštelan²,

Tokmadžić³

et al. 2019

Acta Derm Venerol

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SIGNIFICANCEPsoriasis is a chronic skin disease that affects 2% of the population. Apart from skin symptoms, patients may have psoriatic arthritis and other comorbidities, which can result in grave functional and emotional consequences. Finding a reason for psoriatic plaque formation is the major goal in recent psoriasis investigations. We demonstrated a possible involvement of cytotoxic molecule granulysin in psoriasis pathogenesis. Granulysin is highly expressed in peripheral blood and skin lesions of psoriatic patients in severe form of disease. Resolving the role of this molecule in psoriasis could be a possible way for creating a new target for novel antipsoriatic drug.Psoriasis is considered to be a cytokine-driven immune-mediated disease, although the cell cytotoxicity mechanisms involved remain unrecognized. Herein, we analyzed granulysin expression in different lympho cyte subsets of peripheral blood of 40 psoriatic patients (20 with severe and 20 with mild psoriasis) and seven sample of psoriatic skin. The simultaneous detection of intracellular granulysin and cell surface antigens was performed using flow cytometry in peripheral blood and immunohistochemistry in skin lesions. The frequency of granulysin + cells, mean fluore scence intensity for granulysin, and the frequency of CD8 + T lymphocytes, NK cells, and NKT cells expressing granulysin molecules in peripheral blood were significantly higher in patients with severe psoriasis compared to mild disease and healthy individuals. These were also correlated with disease severity. Furthermore, granulysin + cells, CD8 + granulysin + T lymphocytes, and CD56 + granulysin + NK cells were present in a higher frequency in the epidermal basal cell layer and in the dermal infiltrate of lesional skin as compared to non-lesional and healthy skin. In conclusion, granulysin + cytotoxic cells are upregulated in blood and lesions of patients with psoriasis suggesting the involvement of granulysin mediated cytotoxicity in psoriasis pathogenesis.

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Section: Discussionmentioning

confidence: 65%

“…The presence of GNLY was only recently detected in psoriatic lesions. However, its specific involvement and role in psoriasis pathogenesis is still unclear (9,10).…”

Section: Significancementioning

confidence: 99%

Systemic and Local Increase of Granulysin Expression in Cytotoxic Lymphocytes in Severe Psoriasis

Vičić

Kaštelan²,

Tokmadžić³

et al. 2019

Acta Derm Venerol

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“…5 , 6 It is known that antimicrobial peptides (AMPs), which provide high resistance to skin infection, show increased synthesis in psoriatic lesions. 7 AMP production in the skin is the primary mechanism that protects skin against infections, and AMP levels are increased as a result of microbial infections. 8 Granulysin is a member of the AMP family of cytolytic and proinflammatory peptides.…”

Section: Introductionmentioning

confidence: 99%

The role of GNLY gene polymorphisms in psoriasis pathogenesis

Ermis

Çelik

Solak

et al. 2019

An. Bras. Dermatol.

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Background: Psoriasis is a systemic inflammatory disorder that involves complex pathogenic interactions between the innate and adaptive immune systems. The most accepted mechanism in the etiopathogenesis of psoriasis is the induction of inflammation with keratinocyte hyperproliferation. Granulysin (GNLY) is a cytolytic antimicrobial peptide (AMP) that is secreted together with granzyme and perforin from the granules of human cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. It has been immunohistochemically proven that the expression of granulysin is increased in lesions of psoriasis. Objective: This study aimed to investigate the relationship between psoriasis disease and granulysin gene polymorphisms. Methods: GNLY rs7908 and rs10180391 polymorphisms were studied by PCR-RFLP in 100 psoriasis patients under treatment in the Dermatology Polyclinic of Bulent Ecevit University. In addition, 100 healthy individuals with similar age and sex distribution were used as a control group. Results: In the control group, GNLY rs7908 CC genotype was significantly higher than in psoriasis patients (P= 0.031; OR= 0.305; Cl= 0.305 (0.121 - 0.773). In our study, the genotype distributions in patients and control groups were GNLY rs7908 (SNP) GG (51%, 37%), GC (41%, 44%), CC (8%, 19%); GNLY rs10180391 (SNP) from the CC (41%, 44%), CT (42%, % 41), TT (17%, 15%). Study limitations: The study only included Turkish patients. Conclusion: Our findings showed that GNLY rs7908 CC genotype and C allele had a protective effect against psoriasis and decreased the disease severity (according to PASI score), whereas rs10180391 SNP did not show any effective role in psoriasis pathogenesis.

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“…A study including patients with psoriasis revealed that GNLY expressions in patients were found to be significantly higher in comparison to healthy control group and also, the higher their GNLY levels were related to the duration of disease. According to these results, it was believed that GNLY could have an important role in the pathogenesis of psoriasis 21 .…”

Section: Discussionmentioning

confidence: 96%

Comparison of the plasma levels of cathepsin-L and granulysin between patients with psoriasis and healthy controls

Ayvaz¹,

Gönül²,

Baysak³

et al. 2020

TURKDERM

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Psoriazis, histolojik olarak epidermal hiperproliferasyon ve doğal katil hücreler ile sitotoksik T-hücreleri içeren infiltrasyonun gözlendiği, kronik papüloskuamöz bir hastalıktır. Bu hücrelerin yüksek miktarda perforin, granzim B ve granulizin (GNLY) içeren sitolitik molekülleri taşıdığı gösterilmiştir. Bu moleküllerin psoriazis patogenezindeki rolleri hala tartışmalıdır, serum GNLY ve katepsin-L (CL) seviyelerinin selüler immünite ile ilişkili olabileceği düşünülmektedir. Bu çalışmada psoriaziste hastalık şiddeti ve süresiyle, CL ve GNLY seviyelerinin ilişkisini araştırdık. Gereç ve Yöntem: Prospektif ve randomize bu çalışmaya, Aralık 2014-Ağustos 2015 tarihleri arasında başvuran 40 psoriazis (23 erkek, 17 kadın) hastası ile yaş, cinsiyet uyumlu 40 gönüllü (23 erkek, 17 kadın) dahil edildi. CL ve GNLY serum seviyeleri ELISA yöntemiyle ölçüldü. Bulgular: CL ve GNLY seviyelerinde, psoriazis hastaları ve kontrol grubu arasında istatistiksel olarak anlamlı fark yoktu (p=0,243 ve p=0,606). Düşük Psoriazis Alan Şiddet İndeksi (PAŞİ) skoru (≤10) olan psoriazis hastaları ile yüksek PAŞİ skoru (>10) olan hastalar arasında da istatistiksel olarak anlamlı fark yoktu (p=0,86 ve p=0,61). Background and Design: Psoriasis is a chronic papulosquamous disease where histologically epidermal hyperproliferation and infiltration involving natural killer cells and cytotoxic T-cells are observed. These cells have been shown to carry cytolytic molecules containing high amount of perforin, granzyme B and granulysin (GNLY). The roles of these molecules in the pathogenesis of psoriasis are still disputed, with serum GNLY and cathepsin-l (CL) levels thought to be associated with cellular immunity. In this study, we investigated the relationship between the severity and duration of psoriasis and the levels of CL and GNLY. Materials and Methods: Prospective and randomized study of 40 patients (23 males, 17 females) with psoriasis who admitted to hospital between December 2014 and August 2015, and 40 age and sex-matched healthy controls (23 males, 17 females) were investigated. CL and GNLY serum levels were measured by ELISA method. Results: There was no significant differences in GNLY and CL levels between psoriasis patients and the control group (p=0.243 and p=0.606). There was also no statistically significant difference between psoriasis patients with low Psoriasis Area Severity Index (PASI) (≤10) and those with high PASI (>10) (p=0.86 and p=0.61) score. Conclusion: There are studies that have shown GNLY and CL in the psoriazis are important markers for disease pathogenesis. However, according to the results of this study, CL and GNLY levels are not sufficient markers to indicate the level of cellular immunity and disease severity in psoriasis. Future studies are needed on this subject with a wider range of patients.

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Granulysin expression increases with increasing clinical severity of psoriasis

Cited by 8 publications

References 21 publications

Systemic and Local Increase of Granulysin Expression in Cytotoxic Lymphocytes in Severe Psoriasis

Systemic and Local Increase of Granulysin Expression in Cytotoxic Lymphocytes in Severe Psoriasis

The role of GNLY gene polymorphisms in psoriasis pathogenesis

Comparison of the plasma levels of cathepsin-L and granulysin between patients with psoriasis and healthy controls

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