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  1. Article ; Online: IL-23 induces CLEC5A

    Furuya, Hiroki / Nguyen, Cuong Thach / Chan, Trevor / Marusina, Alina I / Merleev, Alexander A / Garcia-Hernandez, Maria de la Luz / Hsieh, Shie-Liang / Tsokos, George C / Ritchlin, Christopher T / Tagkopoulos, Ilias / Maverakis, Emanual / Adamopoulos, Iannis E

    Journal of autoimmunity

    2024  Volume 143, Page(s) 103167

    Abstract: IL-23-activation of IL-17 producing T cells is involved in many rheumatic diseases. Herein, we investigate the role of IL-23 in the activation of myeloid cell subsets that contribute to skin inflammation in mice and man. IL-23 gene transfer in WT, IL- ... ...

    Abstract IL-23-activation of IL-17 producing T cells is involved in many rheumatic diseases. Herein, we investigate the role of IL-23 in the activation of myeloid cell subsets that contribute to skin inflammation in mice and man. IL-23 gene transfer in WT, IL-23R
    MeSH term(s) Humans ; Arthritis, Psoriatic/pathology ; Interleukin-17/genetics ; Interleukin-17/metabolism ; Neutrophils/metabolism ; Psoriasis ; Skin/pathology ; Dermatitis/pathology ; Inflammation ; Interleukin-23/genetics ; Interleukin-23/metabolism ; Receptors, Cell Surface/metabolism ; Lectins, C-Type/genetics
    Chemical Substances Interleukin-17 ; Interleukin-23 ; CLEC5A protein, human ; Receptors, Cell Surface ; Lectins, C-Type
    Language English
    Publishing date 2024-02-01
    Publishing country England
    Document type Journal Article
    ZDB-ID 639452-8
    ISSN 1095-9157 ; 0896-8411
    ISSN (online) 1095-9157
    ISSN 0896-8411
    DOI 10.1016/j.jaut.2024.103167
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Porphyria cutanea tarda presenting as a lichenoid eruption.

    Toussi, Atrin / Le, Stephanie T / Merleev, Alexander A / Marusina, Alina I / Luxardi, Guillaume / Downing, Lauren / Tran, Monica / Kiuru, Maija H / Maverakis, Emanual

    Photodermatology, photoimmunology & photomedicine

    2020  Volume 37, Issue 3, Page(s) 233–235

    MeSH term(s) Humans ; Lichenoid Eruptions/diagnosis ; Porphyria Cutanea Tarda/complications ; Porphyria Cutanea Tarda/diagnosis
    Language English
    Publishing date 2020-12-22
    Publishing country England
    Document type Letter
    ZDB-ID 1028855-7
    ISSN 1600-0781 ; 0108-9684 ; 0905-4383
    ISSN (online) 1600-0781
    ISSN 0108-9684 ; 0905-4383
    DOI 10.1111/phpp.12640
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Cell-Specific and Variant-Linked Alterations in Expression of ERAP1, ERAP2, and LNPEP Aminopeptidases in Psoriasis.

    Marusina, Alina I / Ji-Xu, Antonio / Le, Stephanie T / Toussi, Atrin / Tsoi, Lam C / Li, Qinyuan / Luxardi, Guillaume / Nava, Jordan / Downing, Lauren / Leal, Annie R / Kuzminykh, Nikolay Y / Kruglinskaya, Olga / Brüggen, Marie-Charlotte / Adamopoulos, Iannis E / Merleev, Alexander A / Gudjonsson, Johann E / Maverakis, Emanual

    The Journal of investigative dermatology

    2023  Volume 143, Issue 7, Page(s) 1157–1167.e10

    Abstract: ERAP1, ERAP2, and LNPEP are aminopeptidases implicated in autoimmune pathophysiology. In this study, we show that ERAP2 is upregulated and ERAP1 is downregulated in patients with psoriasis who are homozygous for autoimmune-linked variants of ERAP. We ... ...

    Abstract ERAP1, ERAP2, and LNPEP are aminopeptidases implicated in autoimmune pathophysiology. In this study, we show that ERAP2 is upregulated and ERAP1 is downregulated in patients with psoriasis who are homozygous for autoimmune-linked variants of ERAP. We also demonstrate that aminopeptidase expression is not uniform in the skin. Specifically, the intracellular antigen-processing aminopeptidases ERAP1 and ERAP2 are strongly expressed in basal and early spinous layer keratinocytes, whereas granular layer keratinocytes expressed predominantly LNPEP, an aminopeptidase specialized in the processing of extracellular antigens for presentation to T cells. In psoriasis, basal keratinocytes also expressed the T-cell- and monocyte-attracting chemokine, CCL2, and the T-cell-supporting cytokine, IL-15. In contrast, TGF-β1 was the major cytokine expressed by healthy control basal keratinocytes. SFRP2-high dermal fibroblasts were also noted to have an ERAP2-high expression phenotype and elevated HLA-C. In psoriasis, the SFRP2-high fibroblast subpopulation also expressed elevated CXCL14. From these results, we postulate that (i) an increased ERAP2/ERAP1 ratio results in altered antigen processing, a potential mechanism by which ERAP risk alleles predispose individuals to autoimmunity; (ii) ERAP2-high expressing cells display a unique major histocompatibility complex-bound peptidome generated from intracellular antigens; and (iii) the granular layer peptidome is skewed toward extracellular antigens.
    MeSH term(s) Humans ; Genetic Predisposition to Disease ; Aminopeptidases/genetics ; Psoriasis/genetics ; Phenotype ; Cytokines/genetics ; Minor Histocompatibility Antigens/genetics ; Polymorphism, Single Nucleotide
    Chemical Substances Aminopeptidases (EC 3.4.11.-) ; Cytokines ; Minor Histocompatibility Antigens ; ERAP1 protein, human (EC 3.4.11.-) ; ERAP2 protein, human (EC 3.4.11.-)
    Language English
    Publishing date 2023-01-28
    Publishing country United States
    Document type Journal Article
    ZDB-ID 80136-7
    ISSN 1523-1747 ; 0022-202X
    ISSN (online) 1523-1747
    ISSN 0022-202X
    DOI 10.1016/j.jid.2023.01.012
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Peripheral γδ T Cells Regulate Neutrophil Expansion and Recruitment in Experimental Psoriatic Arthritis.

    Nguyen, Cuong Thach / Furuya, Hiroki / Das, Dayasagar / Marusina, Alina I / Merleev, Alexander A / Ravindran, Resmi / Jalali, Zahra / Khan, Imran H / Maverakis, Emanual / Adamopoulos, Iannis E

    Arthritis & rheumatology (Hoboken, N.J.)

    2022  Volume 74, Issue 9, Page(s) 1524–1534

    Abstract: Objective: This study was undertaken to identify the mechanistic role of γδ T cells in the pathogenesis of experimental psoriatic arthritis (PsA).: Methods: In this study, we performed interleukin-23 (IL-23) gene transfer in wild-type (WT) and T cell ...

    Abstract Objective: This study was undertaken to identify the mechanistic role of γδ T cells in the pathogenesis of experimental psoriatic arthritis (PsA).
    Methods: In this study, we performed interleukin-23 (IL-23) gene transfer in wild-type (WT) and T cell receptor δ-deficient (TCRδ
    Results: We demonstrated that γδ T cells support systemic granulopoiesis, which is critical for murine PsA-like pathology. Briefly, γδ T cell ablation inhibited the expression of neutrophil chemokines CXCL1 and CXCL2 and neutrophil CD11b+Ly6G+ accumulation in the aforementioned PsA-related tissues. Although significantly reduced expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-17A was detected systemically in TCRδ
    Conclusion: Our findings do not support the notion that tissue-resident γδ T cells initiate the disease but demonstrate a novel role of γδ T cells in neutrophil regulation that can be exploited therapeutically in PsA patients.
    MeSH term(s) Animals ; Arthritis, Experimental/genetics ; Arthritis, Psoriatic/metabolism ; Humans ; Interleukin-17/metabolism ; Mice ; Mice, Inbred C57BL ; Neutrophils/metabolism ; Receptors, Antigen, T-Cell, gamma-delta/metabolism
    Chemical Substances Interleukin-17 ; Receptors, Antigen, T-Cell, gamma-delta
    Language English
    Publishing date 2022-07-21
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2756371-6
    ISSN 2326-5205 ; 2326-5191
    ISSN (online) 2326-5205
    ISSN 2326-5191
    DOI 10.1002/art.42124
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: The Psoriasis Glycome: Differential Expression of Cholesterol Particle Glycans and IgA Glycans Linked to Disease Severity.

    Maverakis, Emanual / Liakos, William / Park, Dayoung / Patel, Forum / Siddiqui, Fariha / Kailemia, Muchena J / Ruhaak, L Renee / Marusina, Alina I / Luxardi, Guillaume / Gudjonsson, Johann E / Le, Stephanie T / Armstrong, April W / Liao, Wilson / Merleev, Alexander A / Lebrilla, Carlito B

    The Journal of investigative dermatology

    2022  Volume 142, Issue 10, Page(s) 2817–2820.e7

    MeSH term(s) Cholesterol ; Humans ; Immunoglobulin A ; Polysaccharides/metabolism ; Psoriasis/diagnosis ; Severity of Illness Index
    Chemical Substances Immunoglobulin A ; Polysaccharides ; Cholesterol (97C5T2UQ7J)
    Language English
    Publishing date 2022-04-22
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 80136-7
    ISSN 1523-1747 ; 0022-202X
    ISSN (online) 1523-1747
    ISSN 0022-202X
    DOI 10.1016/j.jid.2022.03.030
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Anti-Interleukin 23-Based Therapies May Shift Cutaneous Immune Responses: A Case of New-Onset Contact Dermatitis to Carbamates After Guselkumab for Psoriasis.

    Liakos, William / Toussi, Atrin / Le, Stephanie T / Ma, Chelsea / Merleev, Alexander / Marusina, Alina I / Luxardi, Guillaume / Konia, Thomas H / Sood, Apra / Wu, Peggy A / Maverakis, Emanual

    Dermatitis : contact, atopic, occupational, drug

    2021  Volume 32, Issue 6, Page(s) e113–e115

    Language English
    Publishing date 2021-06-17
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2144723-8
    ISSN 2162-5220 ; 1532-8163 ; 1710-3568
    ISSN (online) 2162-5220 ; 1532-8163
    ISSN 1710-3568
    DOI 10.1097/DER.0000000000000765
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Atezolizumab plus stereotactic ablative radiotherapy for medically inoperable patients with early-stage non-small cell lung cancer: a multi-institutional phase I trial.

    Monjazeb, Arta M / Daly, Megan E / Luxardi, Guillaume / Maverakis, Emanual / Merleev, Alexander A / Marusina, Alina I / Borowsky, Alexander / Mirhadi, Amin / Shiao, Stephen L / Beckett, Laurel / Chen, Shuai / Eastham, David / Li, Tianhong / Vick, Logan V / McGee, Heather M / Lara, Frances / Garcia, Leslie / Morris, Leigh Anne / Canter, Robert J /
    Riess, Jonathan W / Schalper, Kurt A / Murphy, William J / Kelly, Karen

    Nature communications

    2023  Volume 14, Issue 1, Page(s) 5332

    Abstract: Stereotactic ablative radiotherapy (SABR) is a standard-of-care for medically-inoperable-early-stage non-small cell lung cancer (NSCLC). One third of patients progress and chemotherapy is rarely used in this population. We questioned if addition of the ... ...

    Abstract Stereotactic ablative radiotherapy (SABR) is a standard-of-care for medically-inoperable-early-stage non-small cell lung cancer (NSCLC). One third of patients progress and chemotherapy is rarely used in this population. We questioned if addition of the immune-checkpoint-inhibitor (ICI) atezolizumab to standard-of-care SABR can improve outcomes. We initiated a multi-institutional single-arm phase I study (NCT02599454) enrolling twenty patients with the primary endpoint of maximum tolerated dose (MTD); secondary endpoints of safety and efficacy; and exploratory mechanistic correlatives. Treatment is well tolerated and full dose atezolizumab (1200 mg) is the MTD. Efficacy signals include early responses (after 2 cycles of ICI, before initiation of SABR) in 17% of patients. Biomarkers of functional adaptive immunity, including T cell activation in the tumor and response to ex-vivo stimulation by circulating T cells, are highly predictive of benefit. These results require validation and are being tested in a phase III randomized trial.
    MeSH term(s) Humans ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Carcinoma, Non-Small-Cell Lung/radiotherapy ; Lung Neoplasms/drug therapy ; Lung Neoplasms/radiotherapy ; Small Cell Lung Carcinoma ; Radiosurgery
    Chemical Substances atezolizumab (52CMI0WC3Y)
    Language English
    Publishing date 2023-09-02
    Publishing country England
    Document type Multicenter Study ; Clinical Trial, Phase I ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-023-40813-w
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  8. Article ; Online: The cutaneous and intestinal microbiome in psoriatic disease.

    Le, Stephanie T / Toussi, Atrin / Maverakis, Natalia / Marusina, Alina I / Barton, Virgina R / Merleev, Alexander A / Luxardi, Guillaume / Raychaudhuri, Siba P / Maverakis, Emanual

    Clinical immunology (Orlando, Fla.)

    2020  Volume 218, Page(s) 108537

    Abstract: Psoriasis (PsO) and psoriatic arthritis (PsA) are chronic immune-mediated inflammatory diseases of multifactorial etiology. In addition to genetic and environmental factors, evidence supports involvement of a dysregulated human microbiome in the ... ...

    Abstract Psoriasis (PsO) and psoriatic arthritis (PsA) are chronic immune-mediated inflammatory diseases of multifactorial etiology. In addition to genetic and environmental factors, evidence supports involvement of a dysregulated human microbiome in the pathogenesis of psoriatic disease. In particular, alterations in the composition of the microbiome, termed dysbiosis, can result in downstream proinflammatory effects in the gut, skin, and joints. Both the cutaneous and intestinal microbial populations are implicated in the pathogenesis of psoriatic disease, although exact mechanisms are unclear. Herein, we review the relationship between the human microbiome and psoriatic disease. Further insight into the functions of the microbiome may allow for greater understanding of inflammatory disease processes and identification of additional therapeutic targets.
    MeSH term(s) Animals ; Gastrointestinal Tract/microbiology ; Humans ; Microbiota ; Psoriasis/microbiology ; Skin/microbiology
    Language English
    Publishing date 2020-07-15
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 1459903-x
    ISSN 1521-7035 ; 1521-6616
    ISSN (online) 1521-7035
    ISSN 1521-6616
    DOI 10.1016/j.clim.2020.108537
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Glycan biomarkers of autoimmunity and bile acid-associated alterations of the human glycome: Primary biliary cirrhosis and primary sclerosing cholangitis-specific glycans.

    Maverakis, Emanual / Merleev, Alexander A / Park, Dayoung / Kailemia, Muchena J / Xu, Gege / Ruhaak, L Renee / Kim, Kyoungmi / Hong, Qiuting / Li, Qiongyu / Leung, Patrick / Liakos, William / Wan, Yu-Jui Yvonne / Bowlus, Christopher L / Marusina, Alina I / Lal, Nelvish N / Xie, Yixuan / Luxardi, Guillaume / Lebrilla, Carlito B

    Clinical immunology (Orlando, Fla.)

    2021  Volume 230, Page(s) 108825

    Abstract: We have recently introduced multiple reaction monitoring (MRM) mass spectrometry as a novel tool for glycan biomarker research and discovery. Herein, we employ this technique to characterize the site-specific glycan alterations associated with primary ... ...

    Abstract We have recently introduced multiple reaction monitoring (MRM) mass spectrometry as a novel tool for glycan biomarker research and discovery. Herein, we employ this technique to characterize the site-specific glycan alterations associated with primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). Glycopeptides associated with disease severity were also identified. Multinomial regression modelling was employed to construct and validate multi-analyte diagnostic models capable of accurately distinguishing PBC, PSC, and healthy controls from one another (AUC = 0.93 ± 0.03). Finally, to investigate how disease-relevant environmental factors can influence glycosylation, we characterized the ability of bile acids known to be differentially expressed in PBC to alter glycosylation. We hypothesize that this could be a mechanism by which altered self-antigens are generated and become targets for immune attack. This work demonstrates the utility of the MRM method to identify diagnostic site-specific glycan classifiers capable of distinguishing even related autoimmune diseases from one another.
    MeSH term(s) Autoimmunity ; B-Lymphocytes/immunology ; B-Lymphocytes/metabolism ; Bile Acids and Salts/blood ; Bile Acids and Salts/immunology ; Biomarkers/blood ; Case-Control Studies ; Cholangitis, Sclerosing/blood ; Cholangitis, Sclerosing/diagnosis ; Cholangitis, Sclerosing/immunology ; Diagnosis, Differential ; Glycomics/methods ; Glycopeptides/blood ; Glycopeptides/immunology ; Glycosylation ; Humans ; Liver Cirrhosis, Biliary/blood ; Liver Cirrhosis, Biliary/diagnosis ; Liver Cirrhosis, Biliary/immunology ; Polysaccharides/blood ; Polysaccharides/immunology ; Spectrometry, Mass, Electrospray Ionization/methods
    Chemical Substances Bile Acids and Salts ; Biomarkers ; Glycopeptides ; Polysaccharides
    Language English
    Publishing date 2021-08-14
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1459903-x
    ISSN 1521-7035 ; 1521-6616
    ISSN (online) 1521-7035
    ISSN 1521-6616
    DOI 10.1016/j.clim.2021.108825
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  10. Article ; Online: Proprotein convertase subtilisin/kexin type 9 is a psoriasis-susceptibility locus that is negatively related to IL36G.

    Merleev, Alexander / Ji-Xu, Antonio / Toussi, Atrin / Tsoi, Lam C / Le, Stephanie T / Luxardi, Guillaume / Xing, Xianying / Wasikowski, Rachael / Liakos, William / Brüggen, Marie-Charlotte / Elder, James T / Adamopoulos, Iannis E / Izumiya, Yoshihiro / Leal, Annie R / Li, Qinyuan / Kuzminykh, Nikolay Y / Kirane, Amanda / Marusina, Alina I / Gudjonsson, Johann E /
    Maverakis, Emanual

    JCI insight

    2022  Volume 7, Issue 16

    Abstract: Proprotein convertase subtilisin/kexin type-9 (PCSK9) is a posttranslational regulator of the LDL receptor (LDLR). Recent studies have proposed a role for PCSK9 in regulating immune responses. Using RNA-Seq-based variant discovery, we identified a ... ...

    Abstract Proprotein convertase subtilisin/kexin type-9 (PCSK9) is a posttranslational regulator of the LDL receptor (LDLR). Recent studies have proposed a role for PCSK9 in regulating immune responses. Using RNA-Seq-based variant discovery, we identified a possible psoriasis-susceptibility locus at 1p32.3, located within PCSK9 (rs662145 C > T). This finding was verified in independently acquired genomic and RNA-Seq data sets. Single-cell RNA-Seq (scRNA-Seq) identified keratinocytes as the primary source of PCSK9 in human skin. PCSK9 expression, however, was not uniform across keratinocyte subpopulations. scRNA-Seq and IHC demonstrated an epidermal gradient of PCSK9, with expression being highest in basal and early spinous layer keratinocytes and lowest in granular layer keratinocytes. IL36G expression followed the opposite pattern, with expression highest in granular layer keratinocytes. PCSK9 siRNA knockdown experiments confirmed this inverse relationship between PCSK9 and IL36G expression. Other immune genes were also linked to PCSK9 expression, including IL27RA, IL1RL1, ISG20, and STX3. In both cultured keratinocytes and nonlesional human skin, homozygosity for PCSK9 SNP rs662145 C > T was associated with lower PCSK9 expression and higher IL36G expression, when compared with heterozygous skin or cell lines. Together, these results support PCSK9 as a psoriasis-susceptibility locus and establish a putative link between PCSK9 and inflammatory cytokine expression.
    MeSH term(s) Humans ; Interleukin-1 ; Proprotein Convertase 9/genetics ; Proprotein Convertase 9/metabolism ; Proprotein Convertases/genetics ; Proprotein Convertases/metabolism ; Psoriasis/genetics ; Serine Endopeptidases/metabolism ; Subtilisins/genetics
    Chemical Substances IL36G protein, human ; Interleukin-1 ; PCSK9 protein, human (EC 3.4.21.-) ; Proprotein Convertase 9 (EC 3.4.21.-) ; Proprotein Convertases (EC 3.4.21.-) ; Serine Endopeptidases (EC 3.4.21.-) ; Subtilisins (EC 3.4.21.-)
    Language English
    Publishing date 2022-08-22
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ISSN 2379-3708
    ISSN (online) 2379-3708
    DOI 10.1172/jci.insight.141193
    Database MEDical Literature Analysis and Retrieval System OnLINE

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