HLA-G Expression in the Skin of Patients with Systemic Sclerosis

Wastowski, Isabela Jubé; Sampaio-Barros, Percival D.; Amstalden, Eliane Maria Ingrid; Palomino, Gustavo Martelli; Marques-Neto, João Francisco; Crispim, Juliane de Almeida; Biral, Ana Cristina Westphal Cheraria; Rassi, Diane Meyre; Carosella, Edgardo D.; Moreau, Philippe; Donadi, Eduardo Antônio

doi:10.3899/jrheum.080552

Cited by 31 publications

(33 citation statements)

References 20 publications

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“…Tissue HLA-G expression has been observed in the skin of patients with systemic sclerosis, who exhibited a lower frequency of vascular cutaneous lesions, telangiectasias, inflammatory polyarthritis and increased survival after a 15-year follow-up [174]. In the demyelinating disorder multiple sclerosis, levels of soluble HLA-G in the cerebrospinal fluid of patients have been inversely associated with imaging findings indicative of disease activity [175].…”

Section: Hla-g Polymorphism and Disease Associationsmentioning

confidence: 99%

Implications of the polymorphism of HLA-G on its function, regulation, evolution and disease association

Donadi

Castelli

Arnaiz‐Villena³

et al. 2010

Cell. Mol. Life Sci.

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303

399

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The HLA-G gene displays several peculiarities that are distinct from those of classical HLA class I genes. The unique structure of the HLA-G molecule permits a restricted peptide presentation and allows the modulation of the cells of the immune system. Although polymorphic sites may potentially influence all biological functions of HLA-G, those present at the promoter and 3′ untranslated regions have been particularly studied in experimental and pathological conditions. The relatively low polymorphism observed in the MHC-G coding region both in humans and apes may represent a strong selective pressure for invariance, whereas, in regulatory regions several lines of evidence support the role of balancing selection. Since HLA-G has immunomodulatory properties, the understanding of gene regulation and the role of polymorphic sites on gene function may permit an individualized approach for the future use of HLA-G for therapeutic purposes.

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Section: Hla-g Polymorphism and Disease Associationsmentioning

confidence: 99%

Implications of the polymorphism of HLA-G on its function, regulation, evolution and disease association

Donadi

Castelli

Arnaiz‐Villena³

et al. 2010

Cell. Mol. Life Sci.

Self Cite

303

399

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“…In addition to the expression of HLA‐G in the dermis, in particular in mononuclear cells in the papillary dermis, whereas it was negative in normal dermis, our major finding was the striking presence of membrane‐bound and soluble forms of HLA‐G in the epidermis of affected areas and, to a lesser extent, in nonaffected skin areas of the patients. In contrast, HLA‐G expression was not observed in skin specimens obtained from healthy individuals, a finding that has been reported consistently by a number of studies 31–33 . Although the molecule has not been detected, HLA‐G mRNA has been detected in normal keratinocyte cultures and in healthy skin specimens 33,34 .…”

Section: Discussionmentioning

confidence: 75%

“…Wastowski et al. (2009) demonstrated HLA‐G expression within epidermal cells in 57% of skin biopsies from patients with systemic sclerosis 32 . HLA‐G expression was associated with more benign disease, i.e.…”

Section: Discussionmentioning

confidence: 99%

Expression of human leucocyte antigen-G primarily targets affected skin of patients with psoriasis

Cardili¹,

Alves

Freitas

et al. 2010

British Journal of Dermatology

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“…First, we have demonstrated that the percentage of HLA-G positive monocytes is increased in SSc patients. Interestingly, HLA-G molecules were detected in epidermal and dermal cells of skin biopsies from approximately 50% of patients with SSc, and HLA-G expression was associated with a lower frequency of cutaneous ulcers, telangiectasias and polyarthralgias [53]. Of note, the percentage of HLA-G-positive monocytes correlated significantly with the plasma levels of sHLA-G molecules.…”

Section: Discussionmentioning

confidence: 97%

Evaluation of membrane-bound and soluble forms of human leucocyte antigen-G in systemic sclerosis

Contini

Negrini

Murdaca

et al. 2018

Clinical and Experimental Immunology

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Systemic sclerosis (SSc) is a complex disease characterized by immune dysregulation, extensive vascular damage and widespread fibrosis. Human leucocyte antigen-G (HLA-G) is a non-classic class I major histocompatibility complex (MHC) molecule characterized by complex immunomodulating properties. HLA-G is expressed on the membrane of different cell lineages in both physiological and pathological conditions. HLA-G is also detectable in soluble form (sHLA-G) deriving from the shedding of surface isoforms (sHLA-G1) or the secretion of soluble isoforms (HLA-G5). Several immunosuppressive functions have been attributed to both membrane-bound and soluble HLA-G molecules. The plasma levels of sHLA-G were higher in SSc patients (444·27 ± 304·84 U/ml) compared to controls (16·74 ± 20·58 U/ml) (P < 0·0001). The plasma levels of transforming growth factor (TGF)-β were higher in SSc patients (18 937 ± 15 217 pg/ml) compared to controls (11 099 ± 6081 pg/ml; P = 0·003), and a significant correlation was found between TGF-β and the plasma levels of total sHLA-G (r = 0·65; P < 0·01), sHLA-G1 (r = 0·60; P = 0·003) and HLA-G5 (r = 0·47; P = 0·02). The percentage of HLA-G-positive monocytes (0·98 ± 1·72), CD4 (0·37 ± 0·68), CD8 (2·05 ± 3·74) and CD4 CD8 double-positive cells (14·53 ± 16·88) was higher in SSc patients than in controls (0·11 ± 0·08, 0·01 ± 0·01, 0·01 ± 0·01 and 0·39 ± 0·40, respectively) (P < 0·0001). These data indicate that in SSc the secretion and/or shedding of soluble HLA-G molecules and the membrane expression of HLA-G by peripheral blood mononuclear cells (PBMC) is clearly elevated, suggesting an involvement of HLA-G molecules in the immune dysregulation of SSc.

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HLA-G Expression in the Skin of Patients with Systemic Sclerosis

Abstract: HLA-G is expressed in skin biopsies from patients with SSc, and this is associated with a better disease prognosis. This suggests a modulatory role of HLA-G in SSc, as observed in other skin disorders.

Cited by 31 publications

References 20 publications

Implications of the polymorphism of HLA-G on its function, regulation, evolution and disease association

Implications of the polymorphism of HLA-G on its function, regulation, evolution and disease association

Expression of human leucocyte antigen-G primarily targets affected skin of patients with psoriasis

Evaluation of membrane-bound and soluble forms of human leucocyte antigen-G in systemic sclerosis

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