Abstract
To determine the prevalence of anti-endothelial cell antibodies (AECA) in children with juvenile idiopathic arthritis (JIA) versus healthy control children. Twenty-eight children with active JIA were studied (ten each with polyarticular and oligoarticular disease, and eight with systemic onset disease). AECA were determined by a cell-based ELISA from samples obtained every 3 months over a 2 year period in each subject. These levels were compared against previously determined levels of von Willebrand factor antigen, fibrin d-dimer, and soluble forms of ICAM-1 and E-selectin, as well as clinical measures of disease activity. AECA were detected in 5/10 oligoarticular, 6/10 polyarticular, and 7/8 systemic JIA subjects and 0/14 controls. Mean levels of AECA were significantly higher in subjects with oligoarticular, and especially systemic disease as compared to polyarticular and control groups when analyzed by ANOVA. AECA are prevalent in JIA and are present more often and at higher levels in systemic disease.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Cassidy IT, Petty RE (2001) Textbook of pediatric rheumatology. WB Saunders Co., Philadelphia
Bloom BJ, Nelson SM, Eisenberg D, Alario AJ (2005) Soluble ICAM-1 and E-selectin as markers of disease activity and endothelial activation in juvenile rheumatoid arthritis. J Rheumatol 32:366–372
Bowyer SL, Ragsdale CG, Sullivan DB (1989) Factor VIII related antigen and childhood rheumatic disease. J Rheumatol 16:1093–1097
Scott JP, Gerber P, Maryjowski MC et al (1985) Evidence for intravascular coagulation in systemic onset, but not polyarticular, juvenile rheumatoid arthritis. Arthritis Rheum 28:256–261
Inamo Y, Pemberton S, Tuddenham EGD, Woo P (1995) Increase of activated factor VllA and haemostatic molecular markers in juvenile chronic arthritis. Br J Rheumatol 34:466–469
Gallistl S, Mangge H, Neuwirth G, Muntean W (1998) Activation of the haemostatic system inchildren with juvenile rheumatoid arthritis correlates with disease activity. Thromb Res 92:267–272
Bloom BJ, Tucker LB, Miller LC, Schaller JG (1998) Fibrin d-dimer as a marker of disease activity in systemic onset juvenile rheumatoid arthritis. J Rheumatol 25:1620–1625
DeBenedetti F, Pignatti P, Massa M et al (1997) Soluble tumor necrosis factor receptor levels reflect coagulation abnormalities in systemic juvenile chronic arthritis. Br J Rheumatol 36:581–588
Mussoni L, Pintucci G, Romano G, DeBenedetti, Massa M, Martini A (1990) Decreased fibrinolytic activity in juvenile chronic arthritis. Decreased fibrinolytic activity in juvenile chronic arthritis. Ann Rheum Dis 49:973–975
Bloom BJ, Miller LC, Tucker LB et al (1999) Soluble adhesion molecules in juvenile rheumatoid arthritis. J Rheumatol 26:2044–2048
Laucella SA, Gaddi E, Balbaryski J et al (1999) Soluble intercellular adhesion molecule-l in paediatric connective tissue diseases. Acta Paediatrica 88:399–403
DeBenedetti F, Vivarelli M, Pignatti P et al (2000) Circulating levels of soluble E-selectin, P-selectin, and intercellular adhesion molecule-l in patients with juvenile idiopathic arthritis. J Rheumatol 27:2246–2250
Dolezalova P, Telekesova P, Nemcova D, Hoza J (2002) Soluble adhesion molecules ICAM-1 and E-selectin in juvenile arthritis: clinical and laboratory correlations. Clin Exp Rheumatol 20:249–254
Chen CY, Tsao CH, Ou LS et al (2002) Comparison of soluble adhesion molecules in juvenile idiopathic arthritis between the active and remission stages. Ann Rheum Dis 61:167–170
Praprotnik S, Blank M, Meroni PL et al (2001) Classification of anti-endothelial cell antibodies into antibodies against microvascular and macrovascular endothelial cells. Arthritis Rheum 44:1484–1494
Blank M, Krause I, Goldkorn T, Praprotnik S et al (1999) Monoclonal anti-endothelial cell antibodies from a patient with Takayasu arteritis activate endothelial cells from large vessels. Arthritis Rheum 42:1421–1432
Damianovich M, Gilburd B, George J et al (1996) Pathogenic role of anti-endothelial cell antibodies in vasculitis. An idiotypic experimental model. J Immunol 156:4946–4951
Del Papa N, Guidali L, Sironi M et al (1996) Anti-endothelial cell IgG antibodies from patients with Wegener’s granulomatosis bind to human endothelial cells in vitro and induce adhesion molecule expression and cytokine excretion. Arthritis Rheum 39:758–766
Tripathy NK, Sinha N, Nityanand S (2003) Anti-annexin antibodies in Takayasu’s arteritis: prevalence and relationship with disease activity. Clin Exp Immunol 134:360–364
Salih AM, Nixon NB, Dawes PT, Mattey DL (1999) Soluble adhesion molecules and anti-endothelial cell antibodies in patients with rheumatoid arthritis complicated by peripheral neuropathy. J Rheumatol 26:551–555
Grunebaum E, Blank M, Cohen S et al (2002) The role of anti-endothelial cell antibodies in Kawasaki disease - in vitro and in vivo studies. Clin Exp Immunol 130:233–240
Guzman J, Fung M, Petty RE (1994) Diagnostic value of anti-neutrophil cytoplasmic and anti-endothelial cell antibodies in early Kawasaki disease. J Pediatr 124:917–920
Nash MC, Shah V, Reader JA, Dillon MJ (1995) Ant-neutrophil cytoplasmic antibodies and anti-endothelial cell antibodies are not increased in Kawasaki disease. Br J Rheumatol 34:882–887
Falcini F, Trapani S, Turchini S et al (1997) Immunologic findings in Kawasaki disease: an evaluation in a cohort of Italian children. Clin ExpRheum 15:685–689
Yang YH, Wang SJ, Chuang YH, Lin YT, Chiang BL (2002) The level of Ig-A antibodies to human umbilical vein endothelial cells can be enhanced by TNF-alpha treatment in children with Henoch-Schonlein purpura. Clin Exp Immunol 130:352–357
Toyoda M, Petrosian A, Jordan SC (1999) Immunologic characterization of anti-endothothelial cell antibodies induced by CMV infection. Transplantation 68:1311–1318
Toyoda M, Galfayan K, Galera OA et al (1997) Cytomegalovirus infection induces anti-endothelial cell antibodies in cardiac and renal allograft recipients. Transplant Immunol 5:104–111
Jamin C, Dugue C, Alard JE et al (2005) Induction of endothelial cell apoptosis by the binding of anti-endothelial cell antibodies to Hsp60 in vasculitis-associated systemic autoimmune diseases. Arthritis Rheum 52:4028–4038
Bloom BJ, Nelson SM, Alario AJ, Miller LC, Schaller JG (2002) Synovial fluid levels of E-selectin and ICAM-1: relationship to joint inflammation in children with chronic arthritis. Rheumatol Int 22:175–177
Frosch M, Metze D, Foell D et al (2005) Early activation of cutaneous vessels and epithelial cells is characteristic of acute systemic onset juvenile idiopathic arthritis. Exp Dermatol 14:259–265
Der-Yuan C, Joung-Liang L, Fang-Ju L, Tsu-Yi H (2005) Association of intercellular adhesion molecule-1 with clinical manifestations and interleukin-18 in patients with active, untreated adult-onset Still’s disease. Arthritis Rheum (Arthritis Care Res) 53:320–327
Kamphuis S, Kuis W, de Jager W et al (2005) Tolerogenic immune responses to novel T-cell epitopes from heat-shock protein 60 in juvenile idiopathic arthritis. Lancet 366:50–56
Author information
Authors and Affiliations
Corresponding author
Additional information
Dr. Bloom supported by a Rhode Island Foundation Medical Sciences Grant and a Lifespan Developmental Grant.
Rights and permissions
About this article
Cite this article
Bloom, B.J., Toyoda, M., Petrosian, A. et al. Anti-endothelial cell antibodies are prevalent in juvenile idiopathic arthritis: implications for clinical disease course and pathogenesis. Rheumatol Int 27, 655–660 (2007). https://doi.org/10.1007/s00296-006-0276-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00296-006-0276-3