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Abstract: We investigated the value of autoantibodies as biomarkers of chronic graft-versus-host disease (cGVHD) by analyzing the autoantibody profiles of 65 patients (34 cGVHD and 31 non-cGVHD) surviving longer than three months after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Autoantibodies to at least one antigen were detected in 45 patients (70.8%), with multiple autoantibodies detected in 30 patients (46.2%). Antinuclear antibodies (ANAs) were the most frequently detected autoantibodies, with a significantly higher prevalence in non-cGVHD patients and cGVHD patients than that in healthy controls (HCs). ANA-nucleolar (ANA-N) was the main immunofluorescence pattern of ANA-positivity in both the non-cGVHD and cGVHD groups. There was a higher prevalence of anti-Ro52-positivity in non-cGVHD and cGVHD patients than in HC. Liver cGVHD was significantly associated with anti-Ro52-positivity. However, cGVHD activity and severity were not associated with the presence of autoantibodies. Similarly, there were no significant differences in overall survival or relapse among the four groups of patients expressing autoantibodies. Our results suggest that autoantibodies have limited value in predicting cGVHD.

自身抗体作为异基因造血干细胞移植后慢性移植物抗宿主病的生物学标志物的潜在价值研究

[1]Admou B, Essaadouni L, Amal S, et al., 2009. Autoantibodies in systemic sclerosis: clinical interest and diagnosis approach. Ann Biol Clin (Paris), 67(3):273-281.

[2]Anasetti C, Logan BR, Lee SJ, et al., 2012. Peripheral-blood stem cells versus bone marrow from unrelated donors. N Engl J Med, 367(16):1487-1496.

[3]Arbuckle MR, McClain MT, Rubertone MV, et al., 2003. Development of autoantibodies before the clinical onset of systemic lupus erythematosus. N Engl J Med, 349(16):1526-1533.

[4]Assandri R, Serana F, Montanelli A, 2017. Development of PBC/SSc overlap syndrome in chronic GVHD patient: immunological implications in the presence of mitochondrial, nucleolar and spindle midzone autoantigens. Gastroenterol Hepatol Bed Bench, 10(4):323-331.

[5]Bell SA, Faust H, Mittermüller J, et al., 1996. Specificity of antinuclear antibodies in scleroderma-like chronic graft-versus-host disease: clinical correlation and histocompatibility locus antigen association. Br J Dermatol, 134(5):848-854.

[6]Catoggio LJ, Bernstein RM, Black CM, et al., 1983. Serological markers in progressive systemic sclerosis: clinical correlations. Ann Rheum Dis, 42(1):23-27.

[7]Chen GL, Arai S, Flowers MED, et al., 2011. A phase 1 study of imatinib for corticosteroid-dependent/refractory chronic graft-versus-host disease: response does not correlate with anti-PDGFRA antibodies. Blood, 118(15):4070-4078.

[8]Defendenti C, Atzeni F, Spina MF, et al., 2011. Clinical and laboratory aspects of Ro/SSA-52 autoantibodies. Autoimmun Rev, 10(3):150-154.

[9]Espinosa A, Dardalhon V, Brauner S, et al., 2009. Loss of the lupus autoantigen Ro52/Trim21 induces tissue inflammation and systemic autoimmunity by disregulating the IL-23-Th17 pathway. J Exp Med, 206(8):1661-1671.

[10]Filipovich AH, Weisdorf D, Pavletic S, et al., 2005. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant, 11(12):945-955.

[11]Finkielman JD, Merkel PA, Schroeder D, et al., 2007. Antiproteinase 3 antineutrophil cytoplasmic antibodies and disease activity in Wegener granulomatosis. Ann Intern Med, 147(9):611-619.

[12]Flynn R, Du J, Veenstra RG, et al., 2014. Increased T follicular helper cells and germinal center B cells are required for cGVHD and bronchiolitis obliterans. Blood, 123(25):3988-3998.

[13]Fraser CJ, Bhatia S, Ness K, et al., 2006. Impact of chronic graft-versus-host disease on the health status of hematopoietic cell transplantation survivors: a report from the bone marrow transplant survivor study. Blood, 108(8):2867-2873.

[14]Fraticelli P, Gabrielli B, Pomponio G, et al., 2014. Low-dose oral imatinib in the treatment of systemic sclerosis interstitial lung disease unresponsive to cyclophosphamide: a phase II pilot study. Arthritis Res Ther, 16(4):R144.

[15]Ho KT, Reveille JD, 2003. The clinical relevance of autoantibodies in scleroderma. Arthritis Res Ther, 5(2):80-93.

[16]Khanna D, Saggar R, Mayes MD, et al., 2011. A one-year, phase I/IIa, open-label pilot trial of imatinib mesylate in the treatment of systemic sclerosis-associated active interstitial lung disease. Arthritis Rheum, 63(11):3540-3546.

[17]Kuzmina Z, Gounden V, Curtis L, et al., 2015. Clinical significance of autoantibodies in a large cohort of patients with chronic graft-versus-host disease defined by NIH criteria. Am J Hematol, 90(2):114-119.

[18]Langford CA, 2004. Antineutrophil cytoplasmic antibodies should not be used to guide treatment in Wegener’s granulomatosis. Clin Exp Rheumatol, 22(6 Suppl 36):S3-S6.

[19]Lee DH, Huh SJ, Yoon HH, et al., 2011. Clinical significance of anti-mitochondrial antibodies in a patient with chronic graft-versus-host disease following hematopoietic stem cell transplantation. Korean J Hematol, 46(3):200-202.

[20]Lepelletier C, Bengoufa D, Lyes Z, et al., 2017. Dermatopulmonary syndrome associated with anti-MDA5 antibodies after allogeneic hematopoietic stem cell transplantation. JAMA Dermatol, 153(2):184-188.

[21]Luo Y, Lai XY, Tan YM, et al., 2009. Reduced-intensity allogeneic transplantation combined with imatinib mesylate for chronic myeloid leukemia in first chronic phase. Leukemia, 23(6):1171-1174.

[22]Maddison PJ, Skinner RP, Pereira RS, et al., 1986. Antinuclear antibodies in the relatives and spouses of patients with systemic sclerosis. Ann Rheum Dis, 45(10):793-799.

[23]Miklos DB, Kim HT, Miller KH, et al., 2005. Antibody responses to H-Y minor histocompatibility antigens correlate with chronic graft-versus-host disease and disease remission. Blood, 105(7):2973-2978.

[24]Montano-Loza AJ, Shums Z, Norman GL, et al., 2012. Prognostic implications of antibodies to Ro/SSA and soluble liver antigen in type 1 autoimmune hepatitis. Liver Int, 32(1):85-92.

[25]Moon JH, Lee SJ, Kim JG, et al., 2009. Clinical significance of autoantibody expression in allogeneic stem-cell recipients. Transplantation, 88(2):242-250.

[26]Muro Y, Sugiura K, Morita Y, et al., 2008. High concomitance of disease marker autoantibodies in anti-DFS70/LEDGF autoantibody-positive patients with autoimmune rheumatic disease. Lupus, 17(3):171-176.

[27]Olivieri A, Locatelli F, Zecca M, et al., 2009. Imatinib for refractory chronic graft-versus-host disease with fibrotic features. Blood, 114(3):709-718.

[28]Panoskaltsis-Mortari A, Tram KV, Price AP, et al., 2007. A new murine model for bronchiolitis obliterans post-bone marrow transplant. Am J Respir Crit Care Med, 176(7):713-723.

[29]Patriarca F, Skert C, Sperotto A, et al., 2006. The development of autoantibodies after allogeneic stem cell transplantation is related with chronic graft-vs-host disease and immune recovery. Exp Hematol, 34(3):389-396.

[30]Pidala J, Kurland B, Chai XY, et al., 2011. Patient-reported quality of life is associated with severity of chronic graft-versus-host disease as measured by NIH criteria: report on baseline data from the Chronic GVHD Consortium. Blood, 117(17):4651-4657.

[31]Przepiorka D, Weisdorf D, Martin P, et al., 1995. 1994 consensus conference on acute GVHD grading. Bone Marrow Transplant, 15(6):825-828.

[32]Quaranta S, Shulman H, Ahmed A, et al., 1999. Autoantibodies in human chronic graft-versus-host disease after hematopoietic cell transplantation. Clin Immunol, 91(1):106-116.

[33]Ruck S, Hilgendorf I, Müller-Hilke B, et al., 2008. Autoantibody-mediated agranulocytosis in association with chronic GVHD. Bone Marrow Transplant, 42(5):359-360.

[34]Sanz J, Arriaga F, Montesinos P, et al., 2007. Autoimmune hemolytic anemia following allogeneic hematopoietic stem cell transplantation in adult patients. Bone Marrow Transplant, 39(9):555-561.

[35]Sarantopoulos S, Stevenson KE, Kim HT, et al., 2009. Altered B-cell homeostasis and excess BAFF in human chronic graft-versus-host disease. Blood, 113(16):3865-3874.

[36]Schulte-Pelkum J, Fritzler M, Mahler M, et al., 2009. Latest update on the Ro/SS-A autoantibody system. Autoimmun Rev, 8(7):632-637.

[37]Sherer Y, Shoenfeld Y, 1998. Autoimmune diseases and autoimmunity post-bone marrow transplantation. Bone Marrow Transplant, 22(9):873-881.

[38]Sinico RA, Radice A, Corace C, et al., 2005. Value of a new automated fluorescence immunoassay (EliA) for PR3 and MPO-ANCA in monitoring disease activity in ANCA-associated systemic vasculitis. Ann N Y Acad Sci, 1050(1):185-192.

[39]Sperotto F, Seguso M, Gallo N, et al., 2017. Anti-DFS70 antibodies in healthy schoolchildren: a follow-up analysis. Autoimmun Rev, 16(2):210-211.

[40]Spiera RF, Gordon JK, Mersten JN, et al., 2011. Imatinib mesylate (Gleevec) in the treatment of diffuse cutaneous systemic sclerosis: results of a 1-year, phase IIa, single-arm, open-label clinical trial. Ann Rheum Dis, 70(6):1003-1009.

[41]Spies-Weisshart B, Schilling K, Böhmer F, et al., 2013. Lack of association of platelet-derived growth factor (PDGF) receptor autoantibodies and severity of chronic graft-versus-host disease (GVHD). J Cancer Res Clin Oncol, 139(8):1397-1404.

[42]Srinivasan M, Flynn R, Price A, et al., 2012. Donor B-cell alloantibody deposition and germinal center formation are required for the development of murine chronic GVHD and bronchiolitis obliterans. Blood, 119(6):1570-1580.

[43]Svegliati S, Olivieri A, Campelli N, et al., 2007. Stimulatory autoantibodies to PDGF receptor in patients with extensive chronic graft-versus-host disease. Blood, 110(1):237-241.

[44]Tyndall A, Dazzi F, 2008. Chronic GVHD as an autoimmune disease. Best Pract Res Clin Haematol, 21(2):281-289.

[45]Wang KS, Kim HT, Nikiforow S, et al., 2017. Antibodies targeting surface membrane antigens in patients with chronic graft-versus-host disease. Blood, 130(26):2889-2899.

[46]Watanabe A, Kodera M, Sugiura K, et al., 2004. Anti-DFS70 antibodies in 597 healthy hospital workers. Arthritis Rheum, 50(3):892-900.

[47]Wesierska-Gadek J, Penner E, Hitchman E, et al., 1992. Nucleolar proteins B23 and C23 as target antigens in chronic graft-versus-host disease. Blood, 79(4):1081-1086.

[48]Zhang AB, Wang Y, Hu C, et al., 2017. Laparoscopic versus open distal pancreatectomy for pancreatic ductal adenocarcinoma: a single-center experience. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 18(6):532-538.