Cerebrospinal fluid amounts of HLA-G in dimeric form are strongly associated to patients with MRI inactive multiple sclerosis

Bortolotti, Daria; Bolzani, Silvia; Castellazzi, Massimiliano; Tamborino, Carmine; Roversi, Gloria; Caniatti, Maria Luisa; Casetta, Ilaria; Gentili, Valentina; Granieri, Enrico; Fainardi, Enrico; Dallocchio, Franco; Bellini, Tiziana; Rizzo, Roberta; Rotola, Antonella; Luca, Dario Di; Seraceni, Silva; Contini, Carlo; Sabbioni, Silvia; Negrini, Massimo; Tognon, Mauro; Antonelli, Tiziana; Groppo, Elisabetta; Gentile, Mauro; Baldi, Eleonora; Caniatti, M. L.; Ceruti, Stefano; Manfrinato, Maria Cristina; Trentini, Alessandro; Miotto, Eliane Correa; Ferracin, Manuela; Mazzoni, Elisa; Pietrobon, Silvia; Masini, Irene; Rotondo, John Charles; Martini, Filippo; Baruzzi, Antônio Cláudio do Amaral; D’Alessandro, R; Michelucci, Roberto; Salvi, Fabrizio; Stecchi, S.; Scandellari, Cinzia; Terzano, Giovanni; Granella, Franco; Nichelli, Paolo Frigio; Sola, Patrizia; Ferraro, D; Vitetta, Francesca; Simone, AM; Bedin, Roberta; Marcello, Norina; Motti, L.; Montepietra, Sara; Guidetti, Donata; Immovilli, Paolo; Montanari, E.; Pesci, Ilaria; Guareschi, A; Greco, G; Santangelo, Mario; Am, Mauro; Malagù, Susanna; Rasi, F; Spadoni, M. A.; Galeotti, M.; Fiorani, L; Neri, Walter; Ravasio, Alessandro; Pasquinelli, M; Gutman, Steven; Monaldini, C.

doi:10.1177/1352458515590647

Cited by 11 publications

(10 citation statements)

References 11 publications

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“…The membrane was incubated with a HRP‐conjugated anti‐mouse antibody (1:5000; Amersham Biosciences, Piscataway, NJ, USA) and developed with the ECL kit (Amersham Biosciences). The images were acquired by Geliance 600 (Perkin Elmer, Massachusetts, USA) . 721.221G cell culture supernatants and HLA‐G‐negative sera were used as positive and negative controls, respectively.…”

Section: Methodsmentioning

confidence: 99%

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Increased levels of soluble HLA‐G molecules in Tunisian patients with chronic hepatitis B infection

Laaribi

Bortolotti

Hannachi

et al. 2017

Journal of Viral Hepatitis

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Hepatitis B virus (HBV) infection is a global health problem. The mechanisms of immune tolerance in HBV infection are still unclear. The host immune response plays a critical role in determining the outcome of HBV infection. Human leucocyte antigen-G (HLA-G) is involved in immunotolerogenic process and infectious diseases. This study aimed to explore the implication of soluble HLA-G (sHLA-G) and its isoforms in HBV infection. Total sHLA-G (including shedding HLA-G1 and HLA-G5) was analysed by ELISA in 95 chronic HBV patients, 83 spontaneously resolvers and 100 healthy controls (HC). To explore the presence of sHLA-G dimers, we performed an immunoprecipitation and a Western blot analysis on positive samples for sHLA-G in ELISA. The serum levels of sHLA-G were significantly increased in patients with chronic HBV patients compared to spontaneously resolvers and HC (P<.0001). Interestingly, we found an increased level of sHLA-G1 in chronic HBV patients than in spontaneously resolvers and HC (P<.001). In addition, the expression of HLA-G5 seems to be higher in the sera of chronic HBV patients than spontaneously resolvers (P=.026). The analysis of HLA-G dimers showed the presence of homodimers in 93% of chronic HBV patients, 67% in spontaneously resolvers and 60% in HC. These results provide evidence that sHLA-G may have a crucial role in the outcome of HBV infection and could be proposed as a biomarker for infection outcome. Based on its tolerogenic function, HLA-G might be considered as a new promising immunotherapeutic approach to treat the chronic infection with HBV.

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Section: Methodsmentioning

confidence: 99%

“…The images were acquired by Geliance 600 (Perkin Elmer, Massachusetts, USA). 13 721.221G cell culture supernatants and HLA-G-negative sera were used as positive and negative controls, respectively.…”

Section: Measurements Of Shla-g Concentrationsmentioning

confidence: 99%

Increased levels of soluble HLA‐G molecules in Tunisian patients with chronic hepatitis B infection

Laaribi

Bortolotti

Hannachi

et al. 2017

Journal of Viral Hepatitis

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“…Dimers of sHLA-G have been also analyzed by Fainardi et al in MS. They demonstrated that HLA-G dimers in cerebrospinal fluid were more frequent in MS patients than in controls and in magnetic resonance imaging (MRI) inactive than in MRI active MS patients, thus suggesting that HLA-G dimers may be implicated in termination of inflammatory response in MS [ 66 ]. Moreover, Mohammadi et al have observed that 14 bp insertion in HLA-G could result in lower plasma HLA-G levels in patients, and they found a significant correlation of HLA-G genotype and its plasma levels with MS susceptibility, thus suggesting a role for HLA-G as a risk factor for MS [ 67 ].…”

Section: Hla-g In Autoimmune/inflammatory Diseasesmentioning

confidence: 99%

Recent Advances in Our Understanding of HLA-G Biology: Lessons from a Wide Spectrum of Human Diseases

Morandi

Rizzo

Fainardi

et al. 2016

Journal of Immunology Research

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109

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HLA-G is a HLA-class Ib molecule with potent immunomodulatory activities, which is expressed in physiological conditions, where modulation of the immune response is required to avoid allograft recognition (i.e., maternal-fetal interface or transplanted patients). However, HLA-G can be expressed de novo at high levels in several pathological conditions, including solid and hematological tumors and during microbial or viral infections, leading to the impairment of the immune response against tumor cells or pathogens, respectively. On the other hand, the loss of HLA-G mediated control of the immune responses may lead to the onset of autoimmune/inflammatory diseases, caused by an uncontrolled activation of the immune effector cells. Here, we have reviewed novel findings on HLA-G functions in different physiological and pathological settings, which have been published in the last two years. These studies further confirmed the important role of this molecule in the modulation of the immune system.

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“…Although HLA‐G heterodimers of different isoforms such as HLA‐G1‐HLA‐G5 or HLA‐G1‐HLA‐G2 have not been detected yet, such dimers might occur through the Cys42 of their α1 domains. SDS‐PAGE under nonreducing conditions are often used for identification of these high‐molecular weight HLA‐G dimers/HLA‐G monomers . Nevertheless, the exclusive usage of such strategies should be considered with caution for the qualitative and quantitative detection of dimers or monomers, as posttranslational modification also increases the size of HLA‐G molecules.…”

Section: Hla‐g Dimers and Oligomers: The Second Dimension Of The Strumentioning

confidence: 99%

Soluble monomers, dimers and HLA‐G‐expressing extracellular vesicles: the three dimensions of structural complexity to use HLA‐G as a clinical biomarker

Nardi

König

Wagner

et al. 2016

HLA

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The HLA-G molecule belongs to the family of nonclassical human leukocyte antigen (HLA) class I. At variance to classical HLA class I, HLA-G displays (i) a low number of nucleotide variations within the coding region, (ii) a high structural diversity, (iii) a restricted peptide repertoire, (iv) a limited tissue distribution and (v) strong immune-suppressive properties. The physiological HLA-G surface expression is restricted to the maternal-fetal interface and to immune-privileged adult tissues. Soluble forms of HLA-G (sHLA-G) are detectable in various body fluids. Cellular activation and pathological processes are associated with an aberrant or a neo-expression of HLA-G/sHLA-G. Functionally, HLA-G and its secreted forms are considered to be key players in the induction of short- and long-term tolerance. Thus, its unique expression profile and tolerance-inducing functions render HLA-G/sHLA-G an attractive biomarker to monitor the systemic health/disease status and disease activity/progression for clinical approaches in disease management and treatments. Here, we place emphasis on (i) the current status of the tolerance-inducing functions by HLA-G/sHLA-G, (ii) the current complexity to implement this molecule as a meaningful clinical biomarker regarding the three dimensions of structural diversity (monomers, dimers and HLA-G-expressing extracellular vesicles) with its functional implications, and (iii) novel and future approaches to detect and quantify sHLA-G structures and functions.

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Cerebrospinal fluid amounts of HLA-G in dimeric form are strongly associated to patients with MRI inactive multiple sclerosis

Abstract: Our findings suggest that HLA-G dimers may be implicated in termination of inflammatory response occurring in MS.

Cited by 11 publications

References 11 publications

Increased levels of soluble HLA‐G molecules in Tunisian patients with chronic hepatitis B infection

Increased levels of soluble HLA‐G molecules in Tunisian patients with chronic hepatitis B infection

Recent Advances in Our Understanding of HLA-G Biology: Lessons from a Wide Spectrum of Human Diseases

Soluble monomers, dimers and HLA‐G‐expressing extracellular vesicles: the three dimensions of structural complexity to use HLA‐G as a clinical biomarker

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