, Ce qui est aussi intriguant est que cette détection fait suite à une capture par le MEM-G9 sans liaison avec HLA-G. Nous avons vérifié que ce ne sont pas des molécules HLA de classe I

. Aussi, Une autre hypothèse est que ces patients possèdent des complexes circulants d'anticorps anti-HLA-G couplé à leur cible et qu'ils soient détectés par la technique MAIGA lors de l'immunoprécipitation. Cependant, l'étape de lavage avant l'immunoprécipitation diminue ce risque. Afin d'éliminer ces anticorps qui pourraient masquer des anticorps anti-HLA-G, des essais d'absorption des anticorps sur les lignées sauvages pourrait être testés. De même, l'identification des anticorps sur cette lignée pourrait avoir un intérêt clinique. Les cibles antigéniques pourraient être identifiées par Western-Blot après immunoprécipitation par MEM-G9 puis après isolement sur gel, par séquençage peptidique. Le Western-Blot pourrait nous, signifie que malgré des lavages stringents, la liaison de MEM-G9 avec des protéines non spécifiques est possible

, En dernier lieu, seulement deux des transplantés possédaient l'haplotype HLA

, 04~UTR2. L'haplotype UTR2 est reconnu comme associé à une diminution d'expression d'HLA-G, vol.5

, Une des hypothèses de survenue d'auto-anticorps et/ou d'alloanticorps anti-HLA-G est l'augmentation d'expression d'HLA-G par le greffon, lors d'un syndrome inflammatoire comme pour HLA-E. De plus, dans notre étude, les allèles HLA-G du greffon, cible de l'allo-immunité, ne sont pas connus et ainsi, l'incompatibilité allélique HLA-G entre l'hôte

E. D. Carosella, HLA-G: from biology to clinical benefits, Trends Immunol, vol.29, issue.3, pp.125-157, 2008.

B. Riteau, HLA-G1 co-expression boosts the HLA class I-mediated NK lysis inhibition, Int Immunol, vol.13, issue.2, pp.193-201, 2001.

F. Gong, Human leukocyte antigen E in human cytomegalovirus infection: friend or foe?, Acta Biochim Biophys Sin (Shanghai), vol.44, issue.7, pp.551-555, 2012.

A. Naji, CD3+CD4low and CD3+CD8low are induced by HLA-G: novel human peripheral blood suppressor T-cell subsets involved in transplant acceptance, Blood, vol.110, issue.12, pp.3936-3984, 2007.

J. Di-cristofaro, HLA-G haplotype structure shows good conservation between different populations and good correlation with high, normal and low soluble HLA-G expression, Hum Immunol, vol.74, issue.2, pp.203-209, 2013.
URL : https://hal.archives-ouvertes.fr/hal-01820051

P. Rousseau, The 14 bp deletion-insertion polymorphism in the 3' UT region of the HLA-G gene influences HLA-G mRNA stability, Hum Immunol, vol.64, issue.11, pp.1005-1015, 2003.

F. Carlini, HLA-G UTR haplotype conservation in the Malian population: association with soluble HLA-G, PLoS One, vol.8, issue.12, p.82517, 2013.
URL : https://hal.archives-ouvertes.fr/hal-00940846

C. Ober, Population genetic studies of HLA-G: allele frequencies and linkage disequilibrium with HLA-A1, J Reprod Immunol, vol.32, issue.2, pp.111-134, 1996.

C. S. Clements, The production, purification and crystallization of a soluble form of the nonclassical MHC HLA-G: the essential role of cobalt, Acta Crystallogr Sect F Struct Biol Cryst Commun, issue.62, pp.70-73, 2006.

S. Coupel, Expression and release of soluble HLA-E is an immunoregulatory feature of endothelial cell activation. Blood, vol.109, pp.2806-2820, 2007.

A. Antoun, Ethnic variability in human leukocyte antigen-E haplotypes, Tissue Antigens, vol.73, issue.1, pp.39-45, 2009.

J. Di-cristofaro, Linkage disequilibrium between HLA-G*0104 and HLA-E*0103 alleles in Tswa Pygmies, Tissue Antigens, vol.77, issue.3, pp.193-200, 2011.
URL : https://hal.archives-ouvertes.fr/halshs-00739718

L. C. Sullivan, The major histocompatibility complex class Ib molecule HLA-E at the interface between innate and adaptive immunity, Tissue Antigens, vol.72, issue.5, pp.415-439, 2008.

J. Di-cristofaro, HLA-E()01:03 Allele in Lung Transplant Recipients Correlates with Higher Chronic Lung Allograft Dysfunction Occurrence, J Immunol Res, p.1910852, 2016.
URL : https://hal.archives-ouvertes.fr/hal-01362578

J. Di-cristofaro, HLA-G*01:04 approximately UTR3 Recipient Correlates With Lower Survival and Higher Frequency of Chronic Rejection After Lung Transplantation, Am J Transplant, vol.15, issue.9, pp.2413-2433, 2015.

M. H. Ravindranath, Antibodies to HLA-E in nonalloimmunized males: pattern of HLA-Ia reactivity of anti-HLA-E-positive sera, J Immunol, vol.185, issue.3, pp.1935-1983, 2010.

R. Goel, Soluble-HLA-E: A follow up biomarker in Takayasu arteritis, independent of HLA-E genotype, Int J Rheum Dis, vol.21, issue.2, pp.532-540, 2018.

M. Courant, The disappointing contribution of anti-human leukocyte antigen donor-specific antibodies characteristics for predicting allograft loss, Nephrol Dial Transplant, vol.33, issue.10, p.1872, 2018.

J. Pratschke, Immunological risk assessment: The key to individualized immunosuppression after kidney transplantation, Transplant Rev (Orlando), vol.30, issue.2, pp.77-84, 2016.

R. Patel and P. I. Terasaki, Significance of the positive crossmatch test in kidney transplantation, N Engl J Med, vol.280, issue.14, pp.735-744, 1969.

H. M. Gebel, Conundrums with FlowPRA beads, vol.16, pp.24-33, 2002.

R. A. Bray, Evolution of HLA antibody detection: technology emulating biology, Immunol Res, vol.29, issue.1-3, pp.41-54, 2004.

C. Lefaucheur, Clinical relevance of preformed HLA donor-specific antibodies in kidney transplantation, Contrib Nephrol, vol.162, pp.1-12, 2009.

Y. M. Zoet, Challenging the golden standard in defining donor-specific antibodies: does the solid phase assay meet the expectations? Tissue Antigens, vol.77, pp.225-233, 2011.

M. Hourmant,

, Nephrol Ther, vol.1, issue.1, pp.7-13, 2005.

F. H. Claas, Clinical relevance of circulating donor-specific HLA antibodies, Curr Opin Organ Transplant, vol.15, issue.4, pp.462-468, 2010.

L. E. Morales-buenrostro, Natural" human leukocyte antigen antibodies found in nonalloimmunized healthy males, Transplantation, vol.86, issue.8, pp.1111-1116, 2008.

M. H. Ravindranath, Antibodies to HLA-E may account for the non-donorspecific anti-HLA class-Ia antibodies in renal and liver transplant recipients, Int Immunol, vol.24, issue.1, pp.43-57, 2012.

M. H. Ravindranath, Therapeutic preparations of IVIg contain naturally occurring anti-HLA-E antibodies that react with HLA-Ia (HLA-A/-B/-Cw) alleles. Blood, vol.121, pp.2013-2041, 2013.

M. H. Ravindranath, The Monospecificity of Novel Anti-HLA-E Monoclonal Antibodies Enables Reliable Immunodiagnosis, Immunomodulation of HLA-E, and Upregulation of CD8+ T Lymphocytes. Monoclon Antib Immunodiagn Immunother, vol.34, pp.135-53, 2015.

P. I. Terasaki, V. D. Mottironi, and E. V. Barnett, Autocytotoxins in lupus, N Engl J Med, vol.283, issue.14, pp.724-732, 1970.

A. Rahman and D. A. Isenberg, Systemic lupus erythematosus, N Engl J Med, vol.358, issue.9, pp.929-968, 2008.

L. A. Criswell, The genetic contribution to systemic lupus erythematosus, Bull NYU Hosp Jt Dis, vol.66, issue.3, pp.176-83, 2008.

B. Zhou, Existence of an immunoglobulin G component of naturally occurring HLA class I antibodies that are not directed against self-antigens in human serum, Tissue Antigens, vol.72, issue.2, pp.98-104, 2008.

V. Jucaud, Serum antibodies to human leucocyte antigen (HLA)-E, HLA-F and HLA-G in patients with systemic lupus erythematosus (SLE) during disease flares: Clinical relevance of HLA-F autoantibodies, Clin Exp Immunol, vol.183, issue.3, pp.326-366, 2016.

V. Jucaud, M. H. Ravindranath, and P. I. Terasaki, Conformational Variants of the Individual HLA-I Antigens on Luminex Single Antigen Beads Used in Monitoring HLA Antibodies: Problems and Solutions, Transplantation, vol.101, issue.4, pp.764-777, 2017.

D. S. Allan, Tetrameric complexes of, J Immunol Methods, vol.268, issue.1, pp.43-50, 2002.
URL : https://hal.archives-ouvertes.fr/hal-00090001

W. B. Tabayoyong and N. Zavazava, Soluble HLA revisited, Leuk Res, vol.31, issue.2, pp.121-126, 2007.

A. Gonzalez, Identification of circulating nonclassic human leukocyte antigen G (HLA-G)-like molecules in exudates, Clin Chem, vol.57, issue.7, pp.1013-1035, 2011.

O. Brugiere, Immunohistochemical study of HLA-G expression in lung transplant recipients, Am J Transplant, vol.9, issue.6, pp.1427-1465, 2009.

P. Moreau, HLA-G gene polymorphism in human placentas: possible association of G*0106 allele with preeclampsia and miscarriage, Biol Reprod, vol.79, issue.3, pp.459-67, 2008.

C. Y. Tan, Paternal contribution of HLA-G*0106 significantly increases risk for pre-eclampsia in multigravid pregnancies, Mol Hum Reprod, vol.14, issue.5, pp.317-341, 2008.

A. Bharat, Antibodies to self-antigens predispose to primary lung allograft dysfunction and chronic rejection, Ann Thorac Surg, vol.90, issue.4, pp.1094-101, 2010.

U. Rao, Prevalence of antibodies to lung self-antigens (Kalpha1 tubulin and collagen V) and donor specific antibodies to HLA in lung transplant recipients and implications for lung transplant outcomes: Single center experience, Transpl Immunol, vol.54, pp.65-72, 2019.

V. Subramanian, Immune response to tissue-restricted self-antigens induces airway inflammation and fibrosis following murine lung transplantation, Am J Transplant, vol.14, issue.10, pp.2359-66, 2014.

D. Dragun, R. Catar, and A. Philippe, Non-HLA antibodies in solid organ transplantation: recent concepts and clinical relevance, Curr Opin Organ Transplant, vol.18, issue.4, pp.430-435, 2013.

R. Ravichandran, The role of donor-derived exosomes in lung allograft rejection, Hum Immunol, vol.80, issue.8, pp.588-594, 2019.

J. Lazarte, Donor human leukocyte antigen-G single nucleotide polymorphisms are associated with post-lung transplant mortality, Eur Respir J, vol.54, issue.2, 2019.

É. Terre,

, Détection des Anticorps anti-HLA-G chez les transplantés d'organes -Impact sur la survenue de rejet aigu et chronique