Akut Romatizmal Ateşli Çocuklarda İnsan Lokosit Antijenleri İle Kapak Tutulumunun ve Romatizmal Kapak Hastalığı Gelişiminin İlişkisi

Giriş: Çalışmamızda akut romatizmal ateş (ARA) tanılı hastalarda ilk atakta kapak tutumu ile HLA antijenleri arasındaki ilişki araştırıldı. Ayrıca aynı ilişkinin izlemde romatizmal kapak hastalığı gelişen hastalarda değerlendirilmesi amaçlandı Materyal ve Metod: 80 hastanın antijen tiplendirmesi Polimerise Chain Reaction (PCR) metoduyla yapıldı. Kontrol grubu tamamen sağlıklı 63 bireyden oluştu. Hastalar ilk ataktaki bulgularına göre alt gruplara ayrıldı.Bulgular: Kontrollerle kıyaslandığında alt gruplardan izole karditli vakalarda ilk atakta mitral yetmezliği (MY) ve aort yetmezliği (AY) birlikte olanlarda HLA DQ8, birinci yıldan sonra MY+AY kalanlarda HLA DR7, DR8 ve DQ8 daha yüksek sıklıkta bulundu. Bu alt grupta birinci yıldan sonra izole MY'si kalanlarda HLA B27 kontrollerden daha yüksek sıklıkta idi. Poliartrit+kardit birlikteliği olup AY+MY olanlarda ilk atakta HLA-B57 ve HLA-B61 daha yüksek sıklıkta saptandı. Bu grupta bir yıldan uzun süreli izlemde izole MY kalanlarda HLA-Cw3, izole AY kalanlarda HLA-DRB1*04 ve DQB1*08 ve AY+MY birlikte devam edenlerde HLA-DRB1*07 daha yüksek sıklıktaydı.Kore+kardit alt grubunda ilk atakta yalnız MY'si olanlarda HLA-B13, AY+MY'si olanlarda HLA-A1 ve B49 daha yüksek sıklıktaydı. Bu grupta bir yılın üzerinde izlemi olup MY sebat edenlerde HLA-B27 sıklığı daha yüksek bulundu.Sonuç: Çalışmamızın sonuçları romatizmal kapak hastalığı gelişmesinde HLA sınıf II antijenlerinin daha belirleyici olabileceğine işaret etti. Her alt grupta daha fazla sayıda hastanın olacağı geniş çalışmalarla sonuçlarımızın doğrulanması gerektiği kanaatine varıldı.

Anahtar Kelimeler:

HLA antijenleri, kapak tutulumu, romatizmal kalp hastalığı

Association of human leucocyte antigens with valvar involvement and rheumatic valvar disease development in children with acute rheumatic fever

Objective: The relation between HLA antigens and valvar involvement at fist atack in patiens with acute rheumatic fever (ARF) was investigated in our study. We also purposed to study the same relation in patients who developed rheumatic valvar disease during follow up period. Material and method: Tissue typing of 80 patiens was performed by Polimerise Chain Reaction (PCR).The control group consisted of 63 healthy persons. The patients were subgrouped accoring to the manifestations at first attack.Results: HLA DQ8 in cases of isolated carditis with aortic (AI) and mitral insufficiency (MI) at first attack, and HLA DR7, DR8 and DQ8 in the same group with remaining aortic+mitral insufficency after the first year, were more frequent than controls. By the first year HLA B27 was more frequent than controls in patients with remaining isolated mitral insufficiency in this subgroup.HLA B57 and HLA B61 were found more frequent in poliartritis+carditis patients with mitral+aortic insufficiency at first attack. After follow up period more than one year, HLA-Cw3 in patients with remaining isolated MI, HLA-DRB1*04 and DQB!*08 in patients with remaining isolated AI and HLA-DRB!*07 in patients with remaining MI+AI were found more ferquent than controls.In chorea+carditis subgroup at first attack, HLA B13 was more frequent in patients with isolated MI, and HLA-A1 and B49 in patients with MI+AI. In this subgroup HLA-B27 was found more ferquent in patients with remaining isolated MI after follow up period more than one year.Conclusion: The results of our study pointed out that HLA Class II antigens may be more determinig on the development of rheumatic valvar disease. But it is concluded that the results of our study should be supported by wider studies including more number of patients in each subgroups.

Keywords:

HLA antigens, valvar involvement, rheumatic heart disease,

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Ortiz EE. Acute rheumatic fever. In Anderson RH, Baker EJ, Macartney FJ, Rigby ML, Shinebourne EA, Taynan M (eds). Paediatric Cardiology. 2nd ed. New York: Churchill Livingstone, 2002: 1713-1732.
Stanevicha V, Eglite J, Zavadska D, Sochnevs A, Shantere R, Gardovska D. HLA class II DR and DQ genotypes and haplotypes associated with rheumatic fever among a clinically homogeneous patient population of Latvian children. Arthritis Res Ther 2007;9:58-67.
Ölmez Ü, Turgay M, Özenirler S ve ark. Association of HLA class I and class II antigens with rheumatic fever in a Turkish population. Scan J Rheumatology 1993; 22: 49-52.
Özkan M, Çarın M, Sönmez G, Şenocak M, Özdemir M, Yakut C. HLA antigens in Turkish race with rheumatic heart disease. Circulation 1993; 87: 1974-1978.
Rajapaske CNA, Halim K, Al-Orainey I, Al-Nozha M, Al-Aska AK. A genetic marker for rheumatic heart disease. Br Heart J 1987; 58: 659-662.
Guilherme L, Köhler KF, Postol E, Kalil J. Genes, autoimmunity and pathogenesis of rheumatic heart disease. Ann Pediatr Cardiol. 2011; 4: 13–21.
American Heart Association. Guidelines for the diagnosis of rheumatic fever. JAMA 1992; 268: 2069-2073.
Khosrashahi HE, Kahramanyol Ö, Doğancı L. HLA and rheumatic fever in Turkish Children. Pediatr Cardiol 1992; 13: 204-207.
Haydardedeoğlu FE, Tutkak H, Köse K, Düzgün N. Genetic susceptibility to rheumatic heart disease and streptococcal pharyngitis: association with HLA-DR alleles. Tissue Antigens 2006; 68:293-296.
Stanevicha V, Eglite J, Sochnevs A, Gardovska D, Zavadska D, Shantere R. HLA class II associations with rheumatic heart disease among clinically homogeneous patients in children in Latvia. Arthritis Res Ther 2003; 5: 340-346.
Guilherme L, Weidebach W, Kiss MH, Snitcowsky R, Kalil J. Association of human leukocyte class II antigens with rheumatic fever or rheumatic heart disease in a Brazilian population. Circulation 1991; 83: 1995-1998.
Cassidy JT, Petty RE: Textbook of pediatric Rheumatology (2nd ed). Philedelphia: Churchill Livingstone; 1999
DiSciassio G, Taranta A. Rheumatic fever in children. Am Heart J 1980; 99: 635-658
Visentainer JE, Pereira FC, Dalalio MM, Tsuneto LT, Donadio PR, Moliterno RA. Association of HLA-DR7 with rheumatic fever in the Brazilian population. J Rheumatol 2000; 27: 1518-1520.
Guedez Y, Kotby A, El-Demellawy M et al. HLA class II associations with rheumatic heart disease are more evident and consistent among clinically homogeneous patients. Circulation 1999; 99: 2784-2790.
Maharaj B, Khedun SM, Hammond MG, Van Der Byl K. HLA-A, B, DR and DQ antigens in Indian patients with severe chronic rheumatic heart disease. Jpn Heart J 1997; 38: 663-668.
Bhat MS, Wani BA, Koul PA, Bisati SD, Khan MA, Shah SU. HLA antigen pattern of Kashmiri patients with rheumatic heart disease. Indian J Med Res 1997; 105: 271-271.
Gu J, Yu B, Zhou J. HLA-DQA1 genes involved in genetic susceptibility to rheumatic fever and rheumatic heart disease in southern Hans (In Chinese). Zhonghua Nei Ke Za Zhi 1997; 36: 308-311.
Afanasev II, Kadyrova RT, Iazdovskii VV. The HLA-associated immunological mechanisms in rheumatic involvment of the myokardium in Russian. Terr Arkh 1995; 67: 56-59.
Koyanagi T, Koga Y, Nishi H et al. DNA typing of HLA class II genes in Japanese patients with rheumatic heart disease. J Mol Cell Cardiol 1996; 28: 1349-1353.
Donadi EA, Smith AG, Louzada-Junior P, Voltarelli JC, Nepom GT. HLA class I and class II profiles of patients presenting with Sydenham’s chorea. J Neurol 2000; 247: 122-128.
Carlquist JF, Ward RH, Meyer KJ, Huseybee D, Feolo M, Anderson J. Immun response factors in rheumatic heart sisease: Meta-analisis of HLA-DR associations and evaluation of additional class II alleles. J Am Coll Cardiol 1995; 26: 452-457.
Ayoub EM, Berrett DJ, Maclaren NK, Krischer JP. Association of class II human histocompatibility leukocyte antigens with rheumatic fever. J Clin İnvest 1986; 77: 2019-2026.
Debaz H, Olivo A, Perez-Luque E et al. DNA analysis of class II alleles in rheumatic heart disease in Mexicans. Hum Immunol 1996; 49: 63.
Wiedebach W, Goldberg AC, Chiarella JM et al. HLA class II antigens in rheumatic fever: analysis of the DR locus by restriction fragment-length polymorphism and oligo-typing. Humm Immunol 1994; 40: 253-258.
Maharaj B, Hammond MG, Appadoo B, Leary WP, Phil D, Pudifin DJ. HLA-A, B, DR and DQ antigens in black patients with severe chronic rheumatic heart disease. Circulation 1987; 76: 259-261.