IL-31 Is Produced by the Malignant T-Cell Population in Cutaneous T-Cell Lymphoma and Correlates with CTCL Pruritus

Singer, Elisha M.; Shin, Daniel B.; Nattkemper, Leigh; Benoit, Bernice M.; Klein, Rachel S.; Didigu, Chuka A.; Loren, Alison W.; Dentchev, Tzvete; Wysocka, Maria; Yosipovitch, Gil; Rook, Alain H.

doi:10.1038/jid.2013.227

Cited by 125 publications

(118 citation statements)

References 13 publications

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“…IL-31 is a newly described cytokine mainly produced by Th2 polarised lymphocytes. This cytokine appears to be important during itching skin conditions since mice overexpressing IL-31 develop severe pruritus and dermatitis (4), and high levels of IL-31 are detected in prurigo nodularis, atopic dermatitis (6) and cutaneous T-cell lymphoma (10). Though our analyses are based only on a single case, elevated expression of IL-31 and another Th2-related cytokine, IL-13, suggests a role of the Th2 pathway in the pathomechanism of this disease.…”

Section: Resultsmentioning

confidence: 99%

A Th2 Cytokine Interleukin-31 Signature in a Case of Sporadic Lichen Amyloidosis

Dousset¹,

Sénéschal²,

Boniface³

et al. 2015

Acta Derm Venerol

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Lichen amyloidosis (LA), a variant form of primary localised cutaneous amyloidosis (PLCA), is a chronic itching skin disease, caused by the extracellular deposition of amyloid proteins in the dermis (1). This entity is clinically characterised by grouped hyperkeratotic papules with itchy lesions usually situated primarily on the shins. The upper back, forearms and thighs can also be involved. While the pathomechanism of PCLA still remains unclear, recent studies have identified in familial PLCA mutations in both the oncostatin M receptor (OSMR) gene, which encodes the OSMRβ (2) and in the interleukin (IL)-31RA gene (3), which encodes the IL-31 receptor α subunit.These 2 subunits constitute the functional receptor for IL-31, a recently discovered cytokine belonging to the IL-6 cytokine family (4). In combination with gp130, OSMRβ is a component shared with the receptor for OSM, another IL-6 family related cytokine. OSMRβ and IL-31RA are widely expressed in keratinocytes, fibroblasts and cutaneous nerves. Based on these new data it has been suggested that OSMRβ or IL-31RA mutants, when stimulated by their ligands OSM or IL-31, trigger signalling abnormalities leading to keratinocyte apoptosis and pruritus (5). Moreover, IL-31 is associated with itchy conditions and overexpression of this cytokine is observed in prurigo and atopic dermatitis (6). Whether expression of IL-31 and/or its receptor is altered in LA is still unknown.Here, we performed an analysis of the OSMR gene and cutaneous expression patterns of cytokines and anti-microbial peptides (AMP) in a 42-year-old woman with a sporadic case of LA. MeTHOdSA lesional skin biopsy showed a hyper plastic epidermis with amorphous, eosinophilic deposits in the papillary dermis with Congo Red staining, confirming the diagnosis of lichen amyloidosis. In subsequent experiments, real-time PCR analysis was performed on additional lesional and non-lesional skin biopsies to analyse the expression profile of genes encoding AMP, cytokines and chemokines as compared to the skin of 6 healthy subjects. ReSuLTS And dISCuSSIOnAlthough we did not detect mutation of the OSMR gene, the transcriptional profile revealed an up-regulation of the Th2-related cytokines IL13 and IL31 genes in lesional skin compared to non-lesional and control skin, while IL4 and TSLP gene expressions were not altered ( Fig. 1 and data not shown). In addition, transcription of a Th2-related chemokine gene, CCL5, was also higher in the patient's lesional skin. Altogether, these data suggest a Th2-biased immune response with an expression of IL-31 in our patient, which has never been reported in this itching skin condition, so far. OSM transcripts were also increased in lesional skin, although the induction was not as prominent as the one observed for IL31 gene (Fig. 1). Among Th1 and Th17-related cytokines, interferon (IFN)-γ gene (IFNG) was the only one upregulated in lesional skin (Fig. 1), whereas IL17 and IL22 expressions were decreased in lesional and non-lesional skin of the patient as compared to no...

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Section: Resultsmentioning

confidence: 99%

A Th2 Cytokine Interleukin-31 Signature in a Case of Sporadic Lichen Amyloidosis

Dousset¹,

Sénéschal²,

Boniface³

et al. 2015

Acta Derm Venerol

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“…Substanz P ist ein sensorisches Neuropeptid, das nachweislich mit dem Schweregrad von Ekzem-Erkrankungen korreliert [39,40]. Aprepitant in einer Dosierung von 80 mg täglich führte zur wirksamen Linderung von Juckreiz bei Patienten mit Sézary-Syndrom, die mit schwerer pruritusbedingter Schlaflosigkeit und Depression stationär behandelt wurden [42]. Die Patienten sprachen schnell auf die Behandlung an.…”

Section: Aprepitantunclassified

“…Durch die Reduktion maligner T-Zellen sinkt auch die Ausschüttung von Chemokinen, die mit der Pathophysiologie des paraneoplastischen Pruritus bei CTCL-Patienten in Zusammenhang gebracht werden. Besonders IL-31, ein von CD4-Helfer-T-Zellen hergestelltes Chemokin, korreliert Untersuchungen zufolge mit Pruritus bei CTCL [42]. Eine Reduktion der IL-31-Serumkonzentration bei Patienten mit CTCL geht nachweislich signifikant mit vermindertem Juckreiz einher [43].…”

Section: Histon-deacetylase-inhibitorenunclassified

Management von paraneoplastischem Pruritus

Rowe¹,

Yosipovitch²

2018

Kompass Dermatol

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Paraneoplastischer Pruritus tritt als systemische Reaktion auf eine zugrunde liegende maligne Erkrankung auf. Paraneoplastischer Pruritus ist am häufigsten mit malignen lymphoproliferativen Erkrankungen sowie soliden Tumoren, die zu Cholestase führen, assoziiert. Paraneoplastischer Pruritus kann sich sowohl ohne primären Hautausschlag manifestieren als auch in Verbindung mit dermatologischen Erkrankungen wie Erythrodermie, Acanthosis nigricans, Dermatomyositis (DM), transitorischer akantholytischer Dermatose (Morbus Grover) oder eruptiver seborrhoischer Keratose. Die Behandlung des paraneoplastischen Pruritus beruht primär auf der Behandlung der zugrunde liegenden malignen Erkrankung, die ursächlich für die systemische Reaktion ist. Wenn die maligne Erkrankung nicht auf Behandlung anspricht, können andere Therapien beim paraneoplastischen Pruritus wirksam sein, wie selektive Serotonin-Wiederaufnahmehemmer, Mirtazapin, Gabapentin, Thalidomid, Opioide, Aprepitant und Histon-Deacetylase-Inhibitoren. Übersetzung aus Curr Probl Dermatol. Basel, Karger, 2016, vol 50, pp 149-154 (DOI: 10.1159/000446060)

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“…A study by Ohmatsu et al [35] demonstrates elevated interleukin-32 mRNA expression levels in mycosis fungoides and suggests that interleukin-32 might contribute to the disease progression. Another study from Singer et al [36] reports on elevated serum levels of interleukin-31 in 14 of 26 pruritic Sézary syndrome patients. In three out of three patients with detectable malignant T-cell clone, the malignant cells were the predominant producers of interleukin-31 and the clinical resolution of pruritus correlated with decreased interleukin-31 levels in the circulation [36].…”

Section: Recent Immunological Studiesmentioning

confidence: 99%

“…Another study from Singer et al [36] reports on elevated serum levels of interleukin-31 in 14 of 26 pruritic Sézary syndrome patients. In three out of three patients with detectable malignant T-cell clone, the malignant cells were the predominant producers of interleukin-31 and the clinical resolution of pruritus correlated with decreased interleukin-31 levels in the circulation [36].…”

Section: Recent Immunological Studiesmentioning

confidence: 99%

Recent advances in primary cutaneous T-cell lymphoma

DeSimone

Sodha

Ignatova

et al. 2015

Current Opinion in Oncology

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PURPOSE OF REVIEW Cutaneous T-cell lymphoma (CTCL) is a heterogeneous group of skin-homing T-cell neoplasms, which represent approximately 75% of all primary cutaneous lymphomas. Currently available drug therapies, when effective, simply control disease and the only option for curing CTCL is stem cell transplant. RECENT FINDINGS In the last year, there has been an incredible effort made to improve the understanding and treatment of CTCL. Recent findings indicate that epigenetic aberrations are integral to active disease. Furthermore, multiple tumor-derived immunological factors have also been shown to inhibit viability, proliferation, and cytokine production of nonmalignant T cells. Several novel targeted therapies show great potential, most promising being antibody drug conjugates targeting surface markers such as CD30 in some CTCL subtypes. Additional attractive targets involve the global modulation of epigenetic markers such as demethylation agents or HDAC inhibitors, either as single agents or in combination therapies. SUMMARY This is a concise review of recent advances in the field of CTCL with special focus on research articles over the preceding year. Purpose of review Cutaneous T-cell lymphoma (CTCL) is a heterogeneous group of skin-homing T-cell neoplasms, which represent approximately 75% of all primary cutaneous lymphomas. Currently available drug therapies, when effective, simply control disease and the only option for curing CTCL is stem cell transplant. Recent findingsIn the last year, there has been an incredible effort made to improve the understanding and treatment of CTCL. Recent findings indicate that epigenetic aberrations are integral to active disease. Furthermore, multiple tumor-derived immunological factors have also been shown to inhibit viability, proliferation, and cytokine production of nonmalignant T cells. Several novel targeted therapies show great potential, most promising being antibody drug conjugates targeting surface markers such as CD30 in some CTCL subtypes. Additional attractive targets involve the global modulation of epigenetic markers such as demethylation agents or HDAC inhibitors, either as single agents or in combination therapies. SummaryThis is a concise review of recent advances in the field of CTCL with special focus on research articles over the preceding year.

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IL-31 Is Produced by the Malignant T-Cell Population in Cutaneous T-Cell Lymphoma and Correlates with CTCL Pruritus

Cited by 125 publications

References 13 publications

A Th2 Cytokine Interleukin-31 Signature in a Case of Sporadic Lichen Amyloidosis

A Th2 Cytokine Interleukin-31 Signature in a Case of Sporadic Lichen Amyloidosis

Management von paraneoplastischem Pruritus

Recent advances in primary cutaneous T-cell lymphoma

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