Pediatric Nephrology

, Volume 22, Issue 8, pp 1083–1094 | Cite as

What’s new in the aetiopathogenesis of vasculitis?



The cause of the majority of childhood vasculitides is unknown although it is likely that a complex interaction between environmental factors and inherited host responses trigger the disease and determine the vasculitis phenotype. Epidemiological clues continue to implicate infectious triggers in Kawasaki syndrome (KS) and Henoch Schőnlein purpura (HSP). Several genetic polymorphisms have now been described in KS and HSP which predispose to disease or predict disease severity. Anti-neutrophil cytoplasmic antibodies (ANCA) are now known to be directly involved in the pathogenesis of vascular injury in ANCA-associated vasculitides, although why some individuals develop ANCA in the first instance is not yet understood. Endothelial injury and repair are active areas of research in vasculitis. It is now possible to track endothelial injury non-invasively in children with vasculitis using surrogate markers of endothelial injury. The vasculogenic pathways involved in vascular repair following vasculitis, including endothelial progenitor cells, are beginning to be studied. It is anticipated that an improved understanding of the aetiopathogenesis of vasculitis in the young will ultimately shape future novel diagnostic and therapeutic approaches and will help us predict which children may develop premature arteriosclerosis in later life.


Aetiology Child Pathogenesis Vasculitis 



I would like to thank Professor Michael Dillon for helpful comments on this manuscript.


  1. 1.
    Brogan PA, Dillon MJ (2000) Vasculitis from the pediatric perspective. Curr Rheumatol Rep 2:411–416PubMedGoogle Scholar
  2. 2.
    Brogan PA, Shah V, Bagga A, Klein N, Dillon MJ (2003) T cell Vbeta repertoires in childhood vasculitides. Clin Exp Immunol 131:517–527PubMedGoogle Scholar
  3. 3.
    Brogan PA, Shah V, Klein N, Dillon MJ (2004) Vbeta-restricted T cell adherence to endothelial cells: a mechanism for superantigen-dependent vascular injury. Arthritis Rheum 50:589–597PubMedGoogle Scholar
  4. 4.
    Pagnoux C, Cohen P, Guillevin L (2006) Vasculitides secondary to infections. Clin Exp Rheumatol 24:S71–S81PubMedGoogle Scholar
  5. 5.
    Naides SJ (2002) Known causes of vasculitis in man. Cleve Clin J Med 69[Suppl 2]:SII15–SII19PubMedGoogle Scholar
  6. 6.
    Gardner-Medwin, JM, Dolezalova P, Cummins C, Southwood TR (2002) Incidence of Henoch-Schonlein purpura, Kawasaki disease, and rare vasculitides in children of different ethnic origins. Lancet 360:1197–1202PubMedGoogle Scholar
  7. 7.
    Yang YH, Hung CF, Hsu CR, Wang LC, Chuang YH, Lin YT, Chiang BL (2005) A nationwide survey on epidemiological characteristics of childhood Henoch-Schonlein purpura in Taiwan. Rheumatology (Oxford) 44:618–622Google Scholar
  8. 8.
    Dolezalova P, Telekesova P, Nemcova D, Hoza J (2004) Incidence of vasculitis in children in the Czech Republic: 2-year prospective epidemiology survey. J Rheumatol 31:2295–2299PubMedGoogle Scholar
  9. 9.
    Brogan PA, Bose A, Burgner D, Shingadia D, Tulloh R, Michie C, Klein N, Booy R, Levin M, Dillon MJ (2002) Kawasaki disease: an evidence based approach to diagnosis, treatment, and proposals for future research. Arch Dis Child 86:286–290PubMedGoogle Scholar
  10. 10.
    Newburger JW, Taubert KA, Shulman ST, Rowley AH, Gewitz MH, Takahashi M, McCrindle BW (2003) Summary and abstracts of the Seventh International Kawasaki Disease Symposium. Hakone Jpn Pediatr Res 53:153–157Google Scholar
  11. 11.
    Shulman ST, Rowley AH (2004) Advances in Kawasaki disease. Eur J Pediatr 163:285–291PubMedGoogle Scholar
  12. 12.
    Bronstein, DE, Dille AN, Austin JP, Williams CM, Palinkas LA, Burns JC (2000) Relationship of climate, ethnicity and socioeconomic status to Kawasaki disease in San Diego County, 1994 through 1998. Pediatr Infect Dis J 19:1087–1091PubMedGoogle Scholar
  13. 13.
    Fujita Y, Nakamura Y, Sakata K, Hara N, Kobayashi M, Nagai M, Yanagawa H, Kawasaki T (1989) Kawasaki disease in families. Pediatrics 84:666–669PubMedGoogle Scholar
  14. 14.
    Harnden A, Alves B, Sheikh A (2002) Rising incidence of Kawasaki disease in England: analysis of hospital admission data. BMJ 324:1424–1425PubMedGoogle Scholar
  15. 15.
    Chang L, Chiang BL, Kao CL, Wu MH, Chen PJ, Berkhout B, Yang HC, Huang LM (2006) Lack of association between infection with a novel human coronavirus (HCoV), HCoV-NH, and Kawasaki disease in Taiwan. J Infect Dis 193:283–286PubMedGoogle Scholar
  16. 16.
    Kim S, Dedeoglu F (2005) Update on pediatric vasculitis. Curr Opin Pediatr 17:695–702PubMedGoogle Scholar
  17. 17.
    Al-Sheyyab M, Batieha A, el-Shanti H, Daoud A (1999) Henoch-Schonlein purpura and streptococcal infection: a prospective case-control study. Ann Trop Paediatr 19:253–255PubMedGoogle Scholar
  18. 18.
    Ayoub EM, McBride J, Schmiederer M, Anderson B (2002) Role of Bartonella henselae in the etiology of Henoch-Schonlein purpura. Pediatr Infect Dis J 21:28–31PubMedGoogle Scholar
  19. 19.
    Cioc AM, Sedmak DD, Nuovo GJ, Dawood MR, Smart G, Magro CM (2002) Parvovirus B19 associated adult Henoch Schonlein purpura. J Cutan Pathol 29:602–607PubMedGoogle Scholar
  20. 20.
    Hidaka H, Okada T, Matsumoto H, Yoshino M, Nagaoka Y, Takeguchi F, Iwasawa H, Tomaru R, Wada T, Shimizu T, Ohtani M, Yamanaka K, Fukutake K, Nakao T (2003) Henoch-Schonlein purpura nephritis in a patient infected with the human immunodeficiency virus. Nippon Jinzo Gakkai Shi 45:387–392PubMedGoogle Scholar
  21. 21.
    Kalman S, Ibrahim AH, Atay A (2005) Henoch-Schonlein purpura in a child following varicella. J Trop Pediatr 51:240–241PubMedGoogle Scholar
  22. 22.
    Watts RA, Gonzalez-Gay MA, Lane SE, Garcia-Porrua C, Bentham G, Scott DG (2001) Geoepidemiology of systemic vasculitis: comparison of the incidence in two regions of Europe. Ann Rheum Dis 60:170–172PubMedGoogle Scholar
  23. 23.
    Watts RA, Lane SE, Scott DG, Koldingsnes W, Nossent H, Gonzalez-Gay MA, Garcia-Porrua C, Bentham GA (2001) Epidemiology of vasculitis in Europe. Ann Rheum Dis 60:1156–1157PubMedGoogle Scholar
  24. 24.
    Mahr AD, Neogi T, Merkel PA (2006) Epidemiology of Wegener’s granulomatosis: Lessons from descriptive studies and analyses of genetic and environmental risk determinants. Clin Exp Rheumatol 24:S82–S91PubMedGoogle Scholar
  25. 25.
    Moulin P, Lehucher-Michel MP (2004) Wegener’s disease and exposure to silica. Study of the physiopathological mechanisms. Presse Med 33:1349–1351PubMedGoogle Scholar
  26. 26.
    Nuyts GD, Van Vlem E, De Vos A, Daelemans RA, Rorive G, Elseviers MM, Schurgers M, Segaert M, D’Haese PC, De Broe ME (1995) Wegener granulomatosis is associated to exposure to silicon compounds: a case-control study. Nephrol Dial Transplant 10:1162–1165PubMedGoogle Scholar
  27. 27.
    Rosenman KD, Moore-Fuller M, Reilly MJ (2000) Kidney disease and silicosis. Nephron 85:14–19PubMedGoogle Scholar
  28. 28.
    Stratta P, Messuerotti A, Canavese C, Coen M, Luccoli L, Bussolati B, Giorda L, Malavenda P, Cacciabue M, Bugiani M, Bo M, Ventura M, Camussi G, Fubini B (2001) The role of metals in autoimmune vasculitis: epidemiological and pathogenic study. Sci Total Environ 270:179–190PubMedGoogle Scholar
  29. 29.
    Haubitz M, Woywodt A, de Groot K, Haller H, Goebel U (2005) Smoking habits in patients diagnosed with ANCA associated small vessel vasculitis. Ann Rheum Dis 64:1500–1502PubMedGoogle Scholar
  30. 30.
    Hogan SL, Satterly KK, Dooley MA, Nachman PH, Jennette JC, Falk RJ (2001) Silica exposure in anti-neutrophil cytoplasmic autoantibody-associated glomerulonephritis and lupus nephritis. J Am Soc Nephrol 12:134–142PubMedGoogle Scholar
  31. 31.
    Lane SE, Watts RA, Bentham G, Innes NJ, Scott DG (2003) Are environmental factors important in primary systemic vasculitis? A case-control study. Arthritis Rheum 48:814–823PubMedGoogle Scholar
  32. 32.
    Merkel PA (1998) Drugs associated with vasculitis. Curr Opin Rheumatol 10:45–50PubMedGoogle Scholar
  33. 33.
    Pankhurst T, Savage CO, Gordon C, Harper L (2004) Malignancy is increased in ANCA-associated vasculitis. Rheumatology 43:1532–1535PubMedGoogle Scholar
  34. 34.
    Barron KS (2002) Kawasaki disease: etiology, pathogenesis, and treatment. Cleve Clin J Med 69[Suppl 2]:SII69–SII78PubMedCrossRefGoogle Scholar
  35. 35.
    Li H, Llera A, Mariuzza RA (1998) Structure-function studies of T-cell receptor-superantigen interactions. Immunol Rev 163:177–186PubMedGoogle Scholar
  36. 36.
    Abe J, Kotzin BL, Jujo K, Melish ME, Glode MP, Kohsaka T, Leung DY (1992) Selective expansion of T cells expressing T-cell receptor variable regions V beta 2 and V beta 8 in Kawasaki disease. Proc Natl Acad Sci USA 89:4066–4070PubMedGoogle Scholar
  37. 37.
    Leung DY, Meissner HC, Shulman ST, Mason WH, Gerber MA, Glode MP, Myones BL, Wheeler JG, Ruthazer R, Schlievert PM (2002) Prevalence of superantigen-secreting bacteria in patients with Kawasaki disease. J Pediatr 140:742–746PubMedGoogle Scholar
  38. 38.
    Matsubara K, Fukaya T, Miwa K, Shibayama N, Nigami H, Harigaya H, Nozaki H, Hirata T, Baba K, Suzuki T, Ishiguro A (2006) Development of serum IgM antibodies against superantigens of Staphylococcus aureus and Streptococcus pyogenes in Kawasaki disease. Clin Exp Immunol 143:427–434PubMedGoogle Scholar
  39. 39.
    Leung DY, Giorno RC, Kazemi LV, Flynn PA, Busse JB (1995) Evidence for superantigen involvement in cardiovascular injury due to Kawasaki syndrome. J Immunol 155:5018–5021PubMedGoogle Scholar
  40. 40.
    Yamashiro Y, Nagata S, Oguchi S, Shimizu T (1996) Selective increase of V beta 2+ T cells in the small intestinal mucosa in Kawasaki disease. Pediatr Res 39:264–266PubMedGoogle Scholar
  41. 41.
    Rowley AH, Shulman ST, Spike BT, Mask CA, Baker SC (2001) Oligoclonal IgA response in the vascular wall in acute Kawasaki disease. J Immunol 166:1334–1343PubMedGoogle Scholar
  42. 42.
    Rowley AH, Baker SC, Shulman ST, Garcia FL, Guzman-Cottrill JA, Chou P, Terai M, Kawasaki T, Kalelkar MB, Crawford SE (2004) Detection of antigen in bronchial epithelium and macrophages in acute Kawasaki disease by use of synthetic antibody. J Infect Dis 190:856–865PubMedGoogle Scholar
  43. 43.
    Ozen S, Bakkaloglu A, Dusunsel R, Soylemezoglu O, Ozaltin F, Poyrazoglu H, Kasapcopur O, Ozkaya O, Yalcinkaya F, Balat A, Kural N, Donmez O, Alpay H, Anarat A, Mir S, Gur-Guven A, Sonmez F, Gok F (2007) Childhood vasculitides in Turkey: a nationwide survey. Clin Rheumatol 26:196–200PubMedGoogle Scholar
  44. 44.
    Popa ER, Tervaert JW (2003) The relation between Staphylococcus aureus and Wegener’s granulomatosis: current knowledge and future directions. Intern Med 42:771–780PubMedGoogle Scholar
  45. 45.
    Stegeman CA, Tervaert JW, Sluiter WJ, Manson WL, de Jong PE, Kallenberg CG (1994) Association of chronic nasal carriage of Staphylococcus aureus and higher relapse rates in Wegener granulomatosis. Ann Intern Med 120:12–17PubMedGoogle Scholar
  46. 46.
    Stegeman CA, Tervaert JW, de Jong PE, Kallenberg CG (1996) Trimethoprim-sulfamethoxazole (co-trimoxazole) for the prevention of relapses of Wegener’s granulomatosis. Dutch Co-Trimoxazole Wegener Study Group. N Engl J Med 335:16–20PubMedGoogle Scholar
  47. 47.
    Popa ER, Stegeman CA, Bos NA, Kallenberg CG, Tervaert JW (2003) Staphylococcal superantigens and T cell expansions in Wegener’s granulomatosis. Clin Exp Immunol 132:496–504PubMedGoogle Scholar
  48. 48.
    Mason JC, Cowie MR, Davies KA, Schofield JB, Cambridge J, Jackson J, So A, Allard SA, Walport MJ (1994) Familial polyarteritis nodosa. Arthritis Rheum 37:1249–1253PubMedGoogle Scholar
  49. 49.
    Dergun M, Kao A, Hauger SB, Newburger JW, Burns JC (2005) Familial occurrence of Kawasaki syndrome in North America. Arch Pediatr Adolesc Med 159:876–881PubMedGoogle Scholar
  50. 50.
    Manganelli P, Giacosa R, Fietta P, Zanetti A, Neri TM (2003) Familial vasculitides: Churg-Strauss syndrome and Wegener’s granulomatosis in 2 first-degree relatives. J Rheumatol 30:618–621PubMedGoogle Scholar
  51. 51.
    Kodama K, Kida O, Morotomi Y, Tanaka K (1986) Male siblings with Takayasu’s arteritis suggest genetic etiology. Heart Vessels 2:51–54PubMedGoogle Scholar
  52. 52.
    Biezeveld MH, Kuipers IM, Geissler J, Lam J, Ottenkamp JJ, Hack CE, Kuijpers TW (2003) Association of mannose-binding lectin genotype with cardiovascular abnormalities in Kawasaki disease. Lancet 361:1268–1270PubMedGoogle Scholar
  53. 53.
    Biezeveld MH, Geissler J, Weverling GJ, Kuipers IM, Lam J, Ottenkamp J, Kuijpers TW (2006) Polymorphisms in the mannose-binding lectin gene as determinants of age-defined risk of coronary artery lesions in Kawasaki disease. Arthritis Rheum 54:369–376PubMedGoogle Scholar
  54. 54.
    Turner MW, Hamvas RM (2000) Mannose-binding lectin: structure, function, genetics and disease associations. Rev Immunogenet 2:305–322PubMedGoogle Scholar
  55. 55.
    Endo M, Ohi H, Ohsawa I, Fujita T, Matsushita M (2000) Complement activation through the lectin pathway in patients with Henoch-Schonlein purpura nephritis. Am J Kidney Dis 35:401–407PubMedGoogle Scholar
  56. 56.
    Bansal PJ, Tobin MC (2004) Neonatal microscopic polyangiitis secondary to transfer of maternal myeloperoxidase-antineutrophil cytoplasmic antibody resulting in neonatal pulmonary hemorrhage and renal involvement. Ann Allergy Asthma Immunol 93:398–401PubMedCrossRefGoogle Scholar
  57. 57.
    Schlieben DJ, Korbet SM, Kimura RE, Schwartz MM, Lewis EJ (2005) Pulmonary-renal syndrome in a newborn with placental transmission of ANCAs. Am J Kidney Dis 45:758–761PubMedGoogle Scholar
  58. 58.
    Xiao H, Heeringa P, Hu P, Liu Z, Zhao M, Aratani Y, Maeda N, Falk RJ, Jennette JC (2002) Antineutrophil cytoplasmic autoantibodies specific for myeloperoxidase cause glomerulonephritis and vasculitis in mice. J Clin Invest 110:955–963PubMedGoogle Scholar
  59. 59.
    Jennette JC, Xiao H, Falk RJ (2006) Pathogenesis of vascular inflammation by anti-neutrophil cytoplasmic antibodies. J Am Soc Nephrol 17:1235–1242PubMedGoogle Scholar
  60. 60.
    Morgan MD, Harper L, Williams J, Savage C (2006) Anti-neutrophil cytoplasm-associated glomerulonephritis. J Am Soc Nephrol 17:1224–1234PubMedGoogle Scholar
  61. 61.
    Harper L, Savage CO (2000) Pathogenesis of ANCA-associated systemic vasculitis. J Pathol 190:349–359PubMedGoogle Scholar
  62. 62.
    Mulder AH, Stegeman CA, Kallenberg CG (1995) Activation of granulocytes by anti-neutrophil cytoplasmic antibodies (ANCA) in Wegener’s granulomatosis: a predominant role for the IgG3 subclass of ANCA. Clin Exp Immunol 101:227–232PubMedGoogle Scholar
  63. 63.
    Savage CO, Harper L, Holland M (2002) New findings in pathogenesis of antineutrophil cytoplasm antibody-associated vasculitis. Curr Opin Rheumatol 14:15–22PubMedGoogle Scholar
  64. 64.
    Tipping PG, Holdsworth SR (2006) T cells in crescentic glomerulonephritis. J Am Soc Nephrol 17:1253–1263PubMedGoogle Scholar
  65. 65.
    Harper L, Ren Y, Savill J, Adu D, Savage CO (2000) Antineutrophil cytoplasmic antibodies induce reactive oxygen-dependent dysregulation of primed neutrophil apoptosis and clearance by macrophages. Am J Pathol 157:211–220PubMedGoogle Scholar
  66. 66.
    Harper L, Cockwell P, Adu D, Savage CO (2001) Neutrophil priming and apoptosis in anti-neutrophil cytoplasmic autoantibody-associated vasculitis. Kidney Int 59:1729–1738PubMedGoogle Scholar
  67. 67.
    Zwaal RF, Schroit AJ (1997) Pathophysiologic implications of membrane phospholipid asymmetry in blood cells. Blood 89:1121–1132PubMedGoogle Scholar
  68. 68.
    Pendergraft WF III, Preston GA, Shah RR, Tropsha A, Carter CW Jr, Jennette JC, Falk RJ (2004) Autoimmunity is triggered by cPR-3(105–201), a protein complementary to human autoantigen proteinase-3. Nat Med 10:72–79PubMedGoogle Scholar
  69. 69.
    Pendergraft WF III, Pressler BM, Jennette JC, Falk RJ, Preston GA (2005) Autoantigen complementarity: a new theory implicating complementary proteins as initiators of autoimmune disease. J Mol Med 83:12–25PubMedGoogle Scholar
  70. 70.
    Senzaki H (2006) The pathophysiology of coronary artery aneurysms in Kawasaki disease: role of matrix metalloproteinases. Arch Dis Child 91:847–851PubMedGoogle Scholar
  71. 71.
    Senzaki H, Masutani S, Kobayashi J, Kobayashi T, Nakano H, Nagasaka H, Sasaki N, Asano H, Kyo S, Yokote Y (2001) Circulating matrix metalloproteinases and their inhibitors in patients with Kawasaki disease. Circulation 104:860–863PubMedGoogle Scholar
  72. 72.
    Hirono K, Foell D, Xing Y, Miyagawa-Tomita S, Ye F, Ahlmann M, Vogl T, Futatani T, Rui C, Yu X, Watanabe K, Wanatabe S, Tsubata S, Uese K, Hashimoto I, Ichida F, Nakazawa M, JRoth J, Miyawaki T (2006) Expression of myeloid-related protein-8 and -14 in patients with acute Kawasaki disease. J Am Coll Cardiol 48:1257–1264PubMedGoogle Scholar
  73. 73.
    Booth AL, Harper L, Hammad T, Bacon P, Griffith M, Levy J, Savage C, Pusey C, Jayne D (2004) Prospective study of TNFalpha blockade with infliximab in anti-neutrophil cytoplasmic antibody-associated systemic vasculitis. Am Soc Nephrol 15:717–721Google Scholar
  74. 74.
    Booth AD, Jayne DR, Kharbanda RK, McEniery CM, Mackenzie IS, Brown J, Wilkinson IB (2004) Infliximab improves endothelial dysfunction in systemic vasculitis: a model of vascular inflammation. Circulation 109:1718–1723PubMedGoogle Scholar
  75. 75.
    Stenbog EV, Windelborg B, Horlyck A, Herlin T (2006) The effect of TNFalpha blockade in complicated, refractory Kawasaki disease. Scand J Rheumatol 35:318–321PubMedGoogle Scholar
  76. 76.
    Wilkinson NM, Erendzhinova E, Zeft A, Cabral DA (2006) Infliximab as rescue therapy in three cases of paediatric Wegener’s granulomatosis. Rheumatology (Oxford) 45:1047–1048Google Scholar
  77. 77.
    Brogan PA, Shah V, Brachet C, Harnden A, Mant D, Klein N, Dillon MJ (2004) Endothelial and platelet microparticles in vasculitis of the young. Arthritis Rheum 50:927–936PubMedGoogle Scholar
  78. 78.
    Bernal-Mizrachi L, Jy W, Fierro C, Macdonough R, Velazques HA, Purow J, Jimenez JJ, Horstman LL, Ferreira A, de Marchena E, Ahn YS (2004) Endothelial microparticles correlate with high-risk angiographic lesions in acute coronary syndromes. Int J Cardiol 97:439–446PubMedGoogle Scholar
  79. 79.
    Jimenez JJ, Jy W, Mauro LM, Horstman LL, Ahn YS (2001) Elevated endothelial microparticles in thrombotic thrombocytopenic purpura: findings from brain and renal microvascular cell culture and patients with active disease. Br J Haematol 112:81–90PubMedGoogle Scholar
  80. 80.
    Brogan PA, Dillon MJ (2004) Endothelial microparticles and the diagnosis of the vasculitides. Intern Med 43:1115–1119PubMedGoogle Scholar
  81. 81.
    Woywodt A, Bahlmann FH, de Groot K, Haller H, Haubitz M (2002) Circulating endothelial cells: life, death, detachment and repair of the endothelial cell layer. Nephrol Dial Transplant 17:1728–1730PubMedGoogle Scholar
  82. 82.
    Woywodt A, Streiber F, de Groot K, Regelsberger H, Haller H, Haubitz M (2003) Circulating endothelial cells as markers for ANCA-associated small-vessel vasculitis. Lancet 361:206–210PubMedGoogle Scholar
  83. 83.
    Woywodt A, Blann AD, Kirsch T, Erdbruegger U, Banzet N, Haubitz M, Dignat-George F (2006) Isolation and enumeration of circulating endothelial cells by immunomagnetic isolation: proposal of a definition and a consensus protocol. J Thromb Haemost 4:671–677PubMedGoogle Scholar
  84. 84.
    Woywodt A, Goldberg C, Kirsch T, de Groot K, Erdbruegger U, Haller H, Haubitz M (2006) Circulating endothelial cells in relapse and limited granulomatous disease due to ANCA associated vasculitis. Ann Rheum Dis 65:164–168PubMedGoogle Scholar
  85. 85.
    Nadar SK, Lip GY, Lee KW, Blann AD (2005) Circulating endothelial cells in acute ischaemic stroke. Thromb Haemost 94:707–712PubMedGoogle Scholar
  86. 86.
    Bull TM, Golpon H, Hebbel RP, Solovey A, Cool CD, Tuder RM, Geraci MW, Voelkel NF (2003) Circulating endothelial cells in pulmonary hypertension. Thromb Haemost 90:698–703PubMedGoogle Scholar
  87. 87.
    Hill JM, Zalos G, Halcox JP, Schenke WH, Waclawiw MA, Quyyumi AA, Finkel T (2003) Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. N Engl J Med 348:593–600PubMedGoogle Scholar
  88. 88.
    Asahara T, Murohara, T Sullivan A, Silver M, van der Zee R, Li T, Witzenbichler B, Schatteman G, Isner JM (1997) Isolation of putative progenitor endothelial cells for angiogenesis. Science 275:964–967PubMedGoogle Scholar
  89. 89.
    Werner N, Kosiol S, Schiegl T, Ahlers P, Walenta K, Link A, Bohm M, Nickenig G (2005) Circulating endothelial progenitor cells and cardiovascular outcomes. N Engl J Med 353:999–1007PubMedGoogle Scholar
  90. 90.
    Herbrig K, Haensel S, Oelschlaegel U, Pistrosch F, Foerster S, Passauer J (2006) Endothelial dysfunction in patients with rheumatoid arthritis is associated with a reduced number and impaired function of endothelial progenitor cells. Ann Rheum Dis 65:157–163PubMedGoogle Scholar
  91. 91.
    Kuwana M, Okazaki Y, Yasuoka H, Kawakami Y, Ikeda Y (2004) Defective vasculogenesis in systemic sclerosis. Lancet 364:603–610PubMedGoogle Scholar
  92. 92.
    Holmen C, Elsheikh E, Stenvinkel P, Qureshi AR, Pettersson E, Jalkanen S, Sumitran-Holgersson S (2005) Circulating inflammatory endothelial cells contribute to endothelial progenitor cell dysfunction in patients with vasculitis and kidney involvement. J Am Soc Nephrol 16:3110–3120PubMedGoogle Scholar
  93. 93.
    Nakatani K, Takeshita S, Tsujimoto H, Kawamura Y, Tokutomi T, Sekine I (2003) Circulating endothelial cells in Kawasaki disease. Clin Exp Immunol 131:536–540PubMedGoogle Scholar
  94. 94.
    Jin H, Aiyer A, Su J, Borgstrom P, Stupack D, Friedlander M, Varner J (2006) A homing mechanism for bone marrow-derived progenitor cell recruitment to the neovasculature. J Clin Invest 116:652–662PubMedGoogle Scholar
  95. 95.
    Kogata N, Arai Y, Pearson JT, Hashimoto K, Hidaka K, Koyama T, Somekawa S, Nakaoka Y, Ogawa M, Adams RH, Okada M, Mochizuki N (2006) Cardiac ischemia activates vascular endothelial cadherin promoter in both preexisting vascular cells and bone marrow cells involved in neovascularization. Circ Res 98:897–904PubMedGoogle Scholar
  96. 96.
    Naoe S, Takahashi K, Masuda H, Tanaka N (1991) Kawasaki disease. With particular emphasis on arterial lesions. Acta Pathol Jpn 41:785–797PubMedGoogle Scholar
  97. 97.
    Dhillon R, Clarkson P, Donald AE, Powe AJ, Nash M, Novelli V, Dillon MJ, Deanfield JE (1996) Endothelial dysfunction late after Kawasaki disease. Circulation 94:2103–2106PubMedGoogle Scholar
  98. 98.
    Albisetti M, Chan AK, McCrindle BW, Wong D, Vegh P, Adams M, Dinyari M, Monagle P, Andrew M (2003) Fibrinolytic response to venous occlusion is decreased in patients after Kawasaki disease. Blood Coagul Fibrin 14:181–186Google Scholar
  99. 99.
    Pilla C, Cheung YF, Brogan PA, Dillon MJ, Redington AN (2000) Chronically reduced arterial distensibility in kawasaki disease: further evidence for the beneficial effects of immunoglobulin (Abstract). Circulation 102[Supplement 2]830–831Google Scholar
  100. 100.
    Cheung YF, Ho MH, Tam SC, Yung TC (2004) Increased high sensitivity C reactive protein concentrations and increased arterial stiffness in children with a history of Kawasaki disease. Heart 90:1281–1285PubMedGoogle Scholar
  101. 101.
    Cheung YF, Brogan PA, Pilla CB, Dillon MJ, Redington AN (2002) Arterial distensibility in children and teenagers: normal evolution and the effect of childhood vasculitis. Arch Dis Child 87:348–351PubMedGoogle Scholar
  102. 102.
    Silva AA, Maeno Y, Hashmi A, Smallhorn JF, Silverman ED, McCrindle BW (2001) Cardiovascular risk factors after Kawasaki disease: a case-control study. J Pediatr 138:400–405PubMedGoogle Scholar
  103. 103.
    Nakamura Y, Yanagawa H, Harada K, Kato H, Kawasaki T (2002) Mortality among persons with a history of Kawasaki disease in Japan: the fifth look. Arch Pediatr Adolesc Med 156:162–165PubMedGoogle Scholar
  104. 104.
    Dillon MJ, Ozen S (2006) A new international classification of childhood vasculitis. Pediatr Nephrol 21:1219–1222PubMedGoogle Scholar
  105. 105.
    Ozen S, Ruperto N, Dillon MJ, Bagga A, Barron K, Davin JC, Kawasaki T, Lindsley C, Petty RE, Prieur AM, Ravelli A, Woo P (2006) EULAR/PReS endorsed consensus criteria for the classification of childhood vasculitides. Ann Rheum Dis 65:936–941PubMedGoogle Scholar
  106. 106.
    Shim YH, Kim HS, Sohn S, Hong YM (2006) Insertion/deletion polymorphism of angiotensin converting enzyme gene in Kawasaki disease. J Korean Med Sci 21:208–211PubMedCrossRefGoogle Scholar
  107. 107.
    Dudley J, Afifi E, Gardner A, Tizard EJ, McGraw ME (2000) Polymorphism of the ACE gene in Henoch-Schonlein purpura nephritis. Pediatr Nephrol 14:218–220PubMedGoogle Scholar
  108. 108.
    Brodkiewicz A, Ciechanowicz A, Urbanska A, Peregud-Pogorzelski J, Dzienski P, Subicka D, Fydryk J (2000) The I/D polymorphism of the ACE gene in children with Henoch-Schoenlein purpura. Pol Merkur Lekarski 8:236–238PubMedGoogle Scholar
  109. 109.
    Amoroso A, Danek G, Vatta S, Crovella S, Berrino M, Guarrera S, Fasano ME, Mazzola G, Amore A, Gianoglio B, Peruzzi L, Coppo R (1998) Polymorphisms in angiotensin-converting enzyme gene and severity of renal disease in Henoch-Schoenlein patients. Italian Group of Renal Immunopathology. Nephrol Dial Transplant 13:3184–3188PubMedGoogle Scholar
  110. 110.
    Park JA, Shin KS, Kim YW (2005) Polymorphism of matrix metalloproteinase-3 promoter gene as a risk factor for coronary artery lesions in Kawasaki disease. J Korean Med Sci 20:607–611PubMedCrossRefGoogle Scholar
  111. 111.
    Zou CC, Zhao ZY, Tang LF, Liang L (2006) Plasma levels of matrix metalloproteinase-9 in Henoch-Schonlein purpura. Scand J Rheumatol 35:52–55PubMedGoogle Scholar
  112. 112.
    Sanders JS, van Goor H, Hanemaaijer R, Kallenberg CG, Stegeman CA (2004) Renal expression of matrix metalloproteinases in human ANCA-associated glomerulonephritis. Nephrol Dial Transplant 19:1412–1419PubMedGoogle Scholar
  113. 113.
    Kariyazono H, Ohno T, Khajoee V, Ihara K, Kusuhara K, Kinukawa N, Mizuno Y, Hara T (2004) Association of vascular endothelial growth factor (VEGF) and VEGF receptor gene polymorphisms with coronary artery lesions of Kawasaki disease. Pediatr Res 56:953–959PubMedGoogle Scholar
  114. 114.
    Rueda B, Perez-Armengol C, Lopez-Lopez S, Garcia-Porrua C, Martin J, Gonzalez-Gay MA (2006) Association between functional haplotypes of vascular endothelial growth factor and renal complications in Henoch-Schonlein purpura. J Rheumatol 33:69–73PubMedGoogle Scholar
  115. 115.
    Li CG, Reynolds I, Ponting JM, Holt PJ, Hillarby MC, Kumar S (1998) Serum levels of vascular endothelial growth factor (VEGF) are markedly elevated in patients with Wegener’s granulomatosis. Br J Rheumatol 37:1303–1306PubMedGoogle Scholar
  116. 116.
    Wu SF, Chang JS, Wan L, Tsai CH, Tsai FJ (2005) Association of IL-1Ra gene polymorphism, but no association of IL-1beta and IL-4 gene polymorphisms, with Kawasaki disease. J Clin Lab Anal 19:99–102PubMedGoogle Scholar
  117. 117.
    Amoli MM, Thomson W, Hajeer AH, Calvino MC, Garcia-Porrua C, Ollier WE, Gonzalez-Gay MA (2002) Interleukin 1 receptor antagonist gene polymorphism is associated with severe renal involvement and renal sequelae in Henoch-Schonlein purpura. J Rheumatol 29:1404–1407PubMedGoogle Scholar
  118. 118.
    Amoli MM, Calvino MC, Garcia-Porrua C, Llorca J, Ollier WE, Gonzalez-Gay MA (2004) Interleukin 1beta gene polymorphism association with severe renal manifestations and renal sequelae in Henoch-Schonlein purpura. J Rheumatol 31:295–298PubMedGoogle Scholar
  119. 119.
    Huang D, Giscombe R, Zhou Y, Lefvert AK (2000) Polymorphisms in CTLA-4 but not tumor necrosis factor-alpha or interleukin 1beta genes are associated with Wegener’s granulomatosis. J Rheumatol 27:397–401PubMedGoogle Scholar
  120. 120.
    Yang J, Li CR, Li YB, Li RX, Sun LB, Huang HJ, Wang GB (2003) The correlation between Kawasaki disease and polymorphisms of Tumor necrosis factor alpha and interleukin-10 gene promoter. Zhonghua Er Ke Za Zhi 41:598–602PubMedGoogle Scholar
  121. 121.
    Yang YH, Lai HJ, Kao CK, Lin YT, Chiang BL (2004) The association between transforming growth factor-beta gene promoter C-509T polymorphism and Chinese children with Henoch-Schonlein purpura. Pediatr Nephrol 19:972–975PubMedGoogle Scholar
  122. 122.
    Amoli MM, Thomson W, Hajee AH, Calvino MC, Garcia-Porrua C, Ollier WE, Gonzalez-Gay MA (2002) Interleukin 8 gene polymorphism is associated with increased risk of nephritis in cutaneous vasculitis. J Rheumatol 29:2367–2370PubMedGoogle Scholar
  123. 123.
    Bartfai Z, Gaede KI, Russell KA, Murakozy G, Muller-Quernheim J, Specks U (2003) Different gender-associated genotype risks of Wegener’s granulomatosis and microscopic polyangiitis. Clin Immunol 109:330–337PubMedGoogle Scholar
  124. 124.
    Burns JC, Shimizu C, Gonzalez E, Kulkarni H, Patel S, Shike H, Sundel RS, Newburger JW, Ahuja SK (2005) Genetic variations in the receptor-ligand pair CCR5 and CCL3L1 are important determinants of susceptibility to Kawasaki disease. J Infect Dis 192:344–349PubMedGoogle Scholar
  125. 125.
    Gershoni-Baruch R, Broza Y, Brik R (2003) Prevalence and significance of mutations in the familial Mediterranean fever gene in Henoch-Schonlein purpura. J Pediatr 143:658–661PubMedGoogle Scholar
  126. 126.
    Tunca M, Akar S, Onen F, Ozdogan H, Kasapcopur O, Yalcinkaya F, Tutar E, Ozen S, Topaloglu R, Yilmaz E, Arici M, Bakkaloglu A, Besbas N, Akpolat T, Dinc A, Erken E (2005) Familial Mediterranean fever (FMF) in Turkey: results of a nationwide multicenter study. Medicine 84:1–11PubMedGoogle Scholar
  127. 127.
    Amoli MM, Thomson W, Hajeer AH, Calvino MC, Garcia-Porrua C, Ollier WE, Gonzalez-Gay MA (2002) HLA-B35 association with nephritis in Henoch-Schonlein purpura. J Rheumatol 29:948–949PubMedGoogle Scholar
  128. 128.
    Yi ZW, Fang XL, Wu XC, He XJ, He QN, Dang XQ, Zhu CP, Mo SH (2006) Role of PAX2 gene polymorphisms in Henoch-Schonlein purpura nephritis. Nephrology 11:42–48PubMedGoogle Scholar
  129. 129.
    Khajoee V, Kariyazono H, Ohno T, Ihara K, Mizuno Y, Kusuhara K, Hara T (2003) Inducible and endothelial constitutive nitric oxide synthase gene polymorphisms in Kawasaki disease. Pediatr Int 45:130–134PubMedGoogle Scholar
  130. 130.
    Martin J, Paco L, Ruiz MP, Lopez-Nevot MA, Garcia-Porrua C, Amoli MM, Calvino MC, Ollier WE, Gonzalez-Gay MA (2005) Inducible nitric oxide synthase polymorphism is associated with susceptibility to Henoch-Schonlein purpura in northwestern Spain. J Rheumatol 32:1081–1085PubMedGoogle Scholar
  131. 131.
    Amoli MM, Mattey DL, Calvino MC, Garcia-Porrua C, Thomson W, Hajeer AH, Ollier WE, Gonzalez-Gay MA (2001) Polymorphism at codon 469 of the intercellular adhesion molecule-1 locus is associated with protection against severe gastrointestinal complications in Henoch-Schonlein purpura. J Rheumatol 28:1014–1018PubMedGoogle Scholar
  132. 132.
    Gencik M, Meller S, Borgmann S, Sitter T, Menezes Saecker AM, Fricke H, Epplen JT (2000) The association of CD18 alleles with anti-myeloperoxidase subtypes of ANCA-associated systemic vasculitides. Clin Immunol 94:9–12PubMedGoogle Scholar
  133. 133.
    Patterson CC, Ross P Jr, Pope-Harman AL, Knight DA, Magro CM (2005) Alpha-1 anti-trypsin deficiency and Henoch-Schonlein purpura associated with anti-neutrophil cytoplasmic and anti-endothelial cell antibodies of immunoglobulin-A isotype. J Cutan Pathol 32:300–306PubMedGoogle Scholar
  134. 134.
    Esnault VL, Testa A, Audrain M, Roge C, Hamidou M, Barrier JH, Sesboue R, Martin JP, Lesavre P (1993) Alpha 1-antitrypsin genetic polymorphism in ANCA-positive systemic vasculitis. Kidney Int 43:1329–1332PubMedGoogle Scholar
  135. 135.
    Esnault VL, Audrain MA, Sesboue R (1997) Alpha-1-antitrypsin phenotyping in ANCA-associated diseases: one of several arguments for protease/antiprotease imbalance in systemic vasculitis. Exp Clin Immunogenet 14:206–213PubMedGoogle Scholar
  136. 136.
    Audrain MA, Sesboue R, Baranger TA, Elliott J, Testa A, Martin JP, Lockwood CM, Esnault VL (2001) Analysis of anti-neutrophil cytoplasmic antibodies (ANCA): frequency and specificity in a sample of 191 homozygous (PiZZ) alpha1-antitrypsin-deficient subjects. Nephrol Dial Transplant 16:39–44PubMedGoogle Scholar
  137. 137.
    Segelmark M, Elzouki AN, Wieslander J, Eriksson S (1995) The PiZ gene of alpha 1-antitrypsin as a determinant of outcome in PR3-ANCA-positive vasculitis. Kidney Int 48:844–850PubMedGoogle Scholar
  138. 138.
    Gencik M, Meller S, Borgmann S, Fricke H (2000) Proteinase 3 gene polymorphisms and Wegener’s granulomatosis. Kidney Int 58:2473–2477PubMedGoogle Scholar
  139. 139.
    Biezeveld M, Geissler J, Merkus M, Kuipers IM, Ottenkamp J, Kuijpers T (2007) The involvement of Fc gamma receptor gene polymorphisms in Kawasaki disease. Clin Exp Immuno 147:106–111Google Scholar
  140. 140.
    Tse WY, Abadeh S, Jefferis R, Savage CO, Adu D (2000) Neutrophil FcgammaRIIIb allelic polymorphism in anti-neutrophil cytoplasmic antibody (ANCA)-positive systemic vasculitis. Clin Exp Immunol 119:574–577PubMedGoogle Scholar
  141. 141.
    Dijstelbloem HM, Scheepers RH, Oost WW, Stegeman CA, van der Pol WL, Sluiter WJ, Kallenberg CG, van de Winkel JG, Tervaert JW (1999) Fcgamma receptor polymorphisms in Wegener’s granulomatosis: risk factors for disease relapse. Arthritis Rheum 42:1823–1827PubMedGoogle Scholar

Copyright information

© IPNA 2007

Authors and Affiliations

  1. 1.Department of Rheumatology Institute of Child Health, Level 6LondonUK

Personalised recommendations