rspНаучно-практическая ревматологияRheumatology Science and Practice1995-44841995-4492IMA-PRESS, LLC10.14412/1995-4484-2012-1109rsp-1029Research ArticleСтатьиArticlesРоль антигенов системы HLA класса I в развитии псориатического артрита и его клинической презентацииRole of HLA class I antigens in the development of psoriatic arthritis and its clinical presentationТрошкинаИ. А.TroshkinaIrina Aleksandrovnatroshkina-irina@yandex.ruБадокинВ. В.BadokinV V-GusevaI AGusevaI A-201215082012504№4 (2012)3439Copyright © Трошкина И.А., Бадокин В.В., Guseva I.A., 20122012Трошкина И.А., Бадокин В.В., Guseva I.A.Troshkina I.A., Badokin V.V., Guseva I.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://rsp.mediar-press.net/rsp/article/view/1029

Цель - исследовать ассоциативную связь HLA-антигенов класса I с предрасположенностью к развитию псориатического артрита (ПсА), тяжестью течения и вариантами суставного синдрома при ПсА. Материал и методы. Включено 99 больных ПсА (56 женщин и 43 мужчины) в возрасте 43,5+13 лет и с медианой длительности заболевания 2 [0,8; 10] года. Олигоартритический вариант наблюдался у 28 больных, полиартритический - у 39, дистальный - у 22, спондилоартритический - у 10. Сформированы две группы больных в зависимости от возраста возникновения псориаза: до 40 лет (n=71) и после 40 лет (n=23). Результаты. У больных ПсА по сравнению с контрольной группой было выявлено повышение частоты HLA-В13 (отношение шансов [ОШ] 2,72; p<0,004), В16 (ОШ 3,95; p<0,0001) и В27 (ОШ 3,2; p<0,003). Выявлена ассоциация вариантов поражения суставов с HLA-антигенами: дистального - с В13 (ОШ 3,38; p<0,02) и В16 (ОШ 3,95; p<0,01), полиартритического - с В16 (ОШ 5,90; p<0,0001) и В27 (ОШ 3,26; p<0,01), спондилоартритического - с В27 (ОШ 6,32; p<0,001). Дебют псориаза в молодом возрасте был ассоциирован с HLA-B13 (ОШ 3,29; p<0,001). Частота выявления антигена В38 (субтип HLA-В16) была повышена при всех рентгенологических стадиях ПсА и составляла при I-ПА стадии 16,4%, при ПБ стадии - 25%, при III-IV стадии -40,9% по сравнению с 8,7% в группе контроля, при этом сила ассоциативной связи увеличивалась с увеличением степени выраженности деструкции в суставах. Заключение. Детальный анализ проведенного исследования выявил различное участие антигенов системы HLA в развитии ПсА и формировании клинических вариантов суставного синдрома.

Objective: to investigate the association of HLA Class I antigens with the predisposition to psoriatic arthritis (PsA) and the severity and types of articular syndrome in PsA. Subjects and methods. The investigation enrolled 99 patients (56 females and 43 males) aged 43.5+13 years with PA with a median duration of 2 (range 0.8-10) years. An oligoarthritic type was observed in 28 patients, polyarthritic, distal, and spondyloarthritic types were present in 28, 39, and 10 patients, respectively. Two patient groups were formed according to the age at onset of psoriasis: 1) 71 patients aged less than 40 years and 2) 23 patients aged over 40 years. Results. As compared with the control group, the patients with PsA were found to have a higher frequency of HLA-B13 (odds ratio [OR] 2.72; p < 0.004), HLA-В16 (OR 3.95; p < 0.0001), and HLA-B27 (OR 3.2; p < 0.003). There was an association of the types of joint injury with HLA antigens: the distal type with HLA-B13 (OR 3.38; p < 0.02) and HLA-В16 (OR 3.95; p < 0.01), the polyarthritic type with HLA-В16 (OR 5.90; p < 0.0001) and HLA-B27 (OR 3.26; p < 0.01), and the spondyloarthritic type with HLA-B27 (OR 6.32; p < 0.001). The young onset of psoriasis was associated with HLA-B13 (OR 3.29; p < 0.001). The detection rate of the B38 antigen (the subtype of HLA-B16) was higher in all X-ray stages of PsA and was 16.4% in Stages I-IIA, 25% in Stage IIB, and 40.9% in Stages III-IV versus 8.7% in the control group, the magnitude of the association being increased with the higher degree of joint destruction. Conclusion. The detailed analysis of the investigation revealed that HLA system antigens were differently involved in the development of PsA and clinical types of articular syndrome.

псориатический артритантигены системы HLA класса Ipsoriatic arthritisHLA class I antigensReferences<div><p>Moll J.M., Wright V. Psoriatic arthritis. Semin Arthr Rheum 1973;3:55-78.</p><p>Gladman D., Espinoza L. International symposium on psoriatic arthtis. J Rheumatol 1992;19:290-1.</p><p>Schon M.P., Boehncke W.H. Psoriasis. N Engl J Med 2005;352:1899-912.</p><p>O'Neill T., Silman A.J. Psoriatic arthritis. Historical background and epidemiology. Baillieres Clin Rheumatol 1994;8:245-61.</p><p>Kavanaugh A., Cassell S. The assessment of disease activity and outcomes in psoriatic arthritis. Clin Exp Rheumatol 2005;39:141-7.</p><p>Willan R. On Cutaneous Diseases. London: Johnson, 1808.</p><p>Moll J.M., Wright V. Familial occurrence of PsA. Ann Rheum Dis 1973;32:181-201.</p><p>Chandran V., Schentag C.T., Brockbank J.E. et al. Familial aggregation of psoriatic arthritis. Ann Rheum Dis 2009;68:664-7.</p><p>Duffin K.C., Chandran V., Gladman D.D. et al. Genetics of psoriasis and psoriatic arthritis: update and future direction (GRAPPA 2007). J Rheumatol 2008;35:1449-53.</p><p>Rahman P., Elder J.T. Genetic epidemiology of psoriasis and psoriatic arthritis. Ann Rheum Dis 2005;64(2):37-9.</p><p>Russell T.J., Schultes L.M., Kuban D.J. Histocompatibility (HL-A) antigens associated with psoriasis. N Engl J Med 1972;287(15):738-40.</p><p>White S.H., Newcomer V.D., Mickey M.R., Terasaki P.I. Disturbance of HL-A antigen frequency in Psoriasis. N Engl J Med 1972;287(15):740-3.</p><p>O'Donnell B.F., O'Loughlin S., Codd M.B., Powell F.C. HLA typing in Irish psoriatics. Ir Med J 1993;86(2):65-8.</p><p>Szczerkowska-Dobosz A., Placek W., Szczerkowska Z., Roszkiewicz J. Psoriasis vulgaris with the early and late onset-HLA phenotype correlations. Arch Immunol Ther Exp (Warsz) 1996;44(4):265-9.</p><p>Kastelan M., Gruber F., Cecuk E. et al. Analysis of HLA antigens in Croatian patients with psoriasis. Acta Derm Venereol Suppl (Stockh) 2000;211:12-3.</p><p>Szczerkowska-Dobosz A. Human leukocyte antigens as psoriasis inheritance and susceptibility markers. Arch Immunol Ther Exp (Warsz) 2005;53(5):428-33.</p><p>Woodrow J.C., Ilchysyn A. HLA antigens in psoriasis and psoriatic arthritis. J Med Genet 1985;22:492-5.</p><p>Jenisch S., Henseler T., Nair R.P. et al. Linkage analysis of human leukocyte antigen (HLA) markers in familial psoriasis: strong disequilibrium effects provide evidence for a major determinant in the HLA-B/-C region. Am J Hum Genet 1998; 63(1):191-9.</p><p>Elder J.T. Fine mapping of the psoriasis susceptibility gene PSORS1: a reassessment of risk associated with a putative risk haplotype lacking HLA-Cw6. J Invest Dermatol 2005;124(5):921-30.</p><p>Nair R.P., Stuart P.E., Nistor I. et al. Sequence and haplotype analysis supports HLA-C as the psoriasis susceptibility 1 gene. Am J Hum Genet 2006;78(5):827-51.</p><p>Rahman P., Roslin N.M., Pelett FJ. et al. High resolution mapping in the major histocompatibility complex region identifies multiple independent novel loci for psoriatic arthritis. Ann Rheum Dis 2011;70(4):690-4.</p><p>Lopez-Larrea C., Torre Alonso J.C. HLA antigens in psoriatic arthritis subtypes of a Spanish population. Ann Rheum Dis 1990;49(5):318-9.</p><p>Gladman D., Farewell T. The role of HLA antigens as indicators of disease progression in psoriatic arthritis. Arthr Rheum 1995;6:845-50.</p><p>Gladman D.D., Farewell V.T., Nadeau T. et al. HLA markers and progression in psoriatic arthritis. J Rheumatol 1998;25(4):730-3.</p><p>Queiro R., Sarasqueta C. Psoriatic spondyloarthropathy: a comparative study between HLA-B27 positive and HLA-B27 negative disease. Semin Arthr Rheum 2002;31(6):413-8.</p><p>Alenius G.M., Jidell E., Nordmark L. et al. Disease manifestations and HLA antigens in psoriatic arthritis in northern Sweden. Clin Rheumatol 2002;21(5):357-62.</p><p>Sakkas L.I., Loqueman N., Bird H. et al. HLA class II and T cell receptor gene polymorphisms in psoriatic arthritis and psoriasis. J Rheumatol 1990;17(11):1487-90.</p><p>Korendowych E., Dixey J., Cox B. et al. The Influence of the HLA-DRB1 rheumatoid arthritis shared epitope on the clinical characteristics and radiological outcome of psoriatic arthritis. J Rheumatol 2003;30(1):96-101.</p><p>Эрдес Ш.Ф. Клинико-генетическое исследование поражения суставов при псориазе: Автореф. дис.. канд. мед. наук. М., 1987; 21 с.</p><p>Димитрова Д., Минев М., Трюнкова Т. HLA-система у больных псориатическим артритом. Тер aрх 1991;63(5):62-3.</p><p>Fournie B., Granel J., Heraud A. et al. HLA-B and psoriatic rheumatism. Study of 193 cases. Rev Rhum Mal Osteoartic 1991; 58(4):269-73.</p><p>Muto M., Date Y., Ichimiya M. et al. Significance of antibodies to streptococcal M protein in psoriatic arthritis and their association with HLA-A*0207. Tissue Antigens 1996;48(6):645-50.</p><p>Elkayam O., Segal R., Caspi D. et al. Human leukocyte antigen distribution in Israeli patients with psoriatic arthritis. Rheumatol Int 2004;24(2):93-7.</p><p>Grubic Z., Peric P., Cecuk-Jelicic E. et al. The distribution of HLA alleles class I and class II among patientes with psoriatic arthritis in Croatia. Reumatizam 2004;1(1):5-11.</p><p>Imre K, Koo E, Sesztak M. et al. Genetics in patients with psoriatic arthritis. Orv Hetil 2006;147(50):2415-9.</p><p>Liao H.T., Lin K.C., Chang Y.T. et al. Human leukocyte antigen and clinical and demographic characteristics in psoriatic arthritis and psoriasis in Chinese patients. J Rheumatol 2008;35(5):891-5.</p><p>Hohler T., Schneider P.M., Rittner C. et al. LMP polymorphisms do not influence disease expression in psoriatic arthritis. Clin Exp Rheumatol 1996;14(6):661-4.</p><p>Marsal S., Armadans-Gil L., Nartinez M. et al. Clinical, radiographic and HLA associations as markers for different patterns of psoriatic arthritis. Rheumatology (Oxford) 1999;38(4):332-7.</p><p>Salvarani C., Macchioni P.L., Zizzi F. et al. Clinical subgroups and HLA antigens in Italian patients with psoriatic arthritis. Clin Exp Rheumatol 1989;7(4):391-6.</p><p>Яздовский В.В., Воронин А.В., Алексеев Л.П. HLA-генетический профиль русской популяции. Иммунология 1998;2:30-2.</p><p>Агабабова Э.Р., Бадокин В.В., Эрдес Ш.Ф. и др. Разработка и апробация диагностических критериев псориатического артрита. Тер арх 1988;12:117-21.</p><p>Queiro R., Alperi M., Lopez A. et al. Clinical expression, but not disease outcome, may vary according to age at disease onset in psoriatic spondylitis. Joint Bone Spine 2008;75(5):544-7.</p><p>Espinoza L.R., Vasey F.B., Gaylord S.W. et al. Histocompatibility typing in the seronegative spondyloarthropathies: a survey. Semin Arthr Rheum 1982;11:375-81.</p><p>Анищенко М.А., Мельников Б.И., Ярулин Ф.Г. HLA-антигены I класса у больных вульгарным псориазом. Иммунология 1988;3:45-7.</p></div><br /><div><p>Moll J.M., Wright V. Psoriatic arthritis. Semin Arthr Rheum 1973;3:55-78.</p><p>Gladman D., Espinoza L. International symposium on psoriatic arthtis. J Rheumatol 1992;19:290-1.</p><p>Schon M.P., Boehncke W.H. Psoriasis. N Engl J Med 2005;352:1899-912.</p><p>O'Neill T., Silman A.J. Psoriatic arthritis. Historical background and epidemiology. Baillieres Clin Rheumatol 1994;8:245-61.</p><p>Kavanaugh A., Cassell S. The assessment of disease activity and outcomes in psoriatic arthritis. Clin Exp Rheumatol 2005;39:141-7.</p><p>Willan R. On Cutaneous Diseases. London: Johnson, 1808.</p><p>Moll J.M., Wright V. Familial occurrence of PsA. Ann Rheum Dis 1973;32:181-201.</p><p>Chandran V., Schentag C.T., Brockbank J.E. et al. Familial aggregation of psoriatic arthritis. Ann Rheum Dis 2009;68:664-7.</p><p>Duffin K.C., Chandran V., Gladman D.D. et al. Genetics of psoriasis and psoriatic arthritis: update and future direction (GRAPPA 2007). J Rheumatol 2008;35:1449-53.</p><p>Rahman P., Elder J.T. Genetic epidemiology of psoriasis and psoriatic arthritis. Ann Rheum Dis 2005;64(2):37-9.</p><p>Russell T.J., Schultes L.M., Kuban D.J. Histocompatibility (HL-A) antigens associated with psoriasis. N Engl J Med 1972;287(15):738-40.</p><p>White S.H., Newcomer V.D., Mickey M.R., Terasaki P.I. Disturbance of HL-A antigen frequency in Psoriasis. N Engl J Med 1972;287(15):740-3.</p><p>O'Donnell B.F., O'Loughlin S., Codd M.B., Powell F.C. HLA typing in Irish psoriatics. Ir Med J 1993;86(2):65-8.</p><p>Szczerkowska-Dobosz A., Placek W., Szczerkowska Z., Roszkiewicz J. Psoriasis vulgaris with the early and late onset-HLA phenotype correlations. Arch Immunol Ther Exp (Warsz) 1996;44(4):265-9.</p><p>Kastelan M., Gruber F., Cecuk E. et al. Analysis of HLA antigens in Croatian patients with psoriasis. Acta Derm Venereol Suppl (Stockh) 2000;211:12-3.</p><p>Szczerkowska-Dobosz A. Human leukocyte antigens as psoriasis inheritance and susceptibility markers. Arch Immunol Ther Exp (Warsz) 2005;53(5):428-33.</p><p>Woodrow J.C., Ilchysyn A. HLA antigens in psoriasis and psoriatic arthritis. J Med Genet 1985;22:492-5.</p><p>Jenisch S., Henseler T., Nair R.P. et al. Linkage analysis of human leukocyte antigen (HLA) markers in familial psoriasis: strong disequilibrium effects provide evidence for a major determinant in the HLA-B/-C region. Am J Hum Genet 1998; 63(1):191-9.</p><p>Elder J.T. Fine mapping of the psoriasis susceptibility gene PSORS1: a reassessment of risk associated with a putative risk haplotype lacking HLA-Cw6. J Invest Dermatol 2005;124(5):921-30.</p><p>Nair R.P., Stuart P.E., Nistor I. et al. Sequence and haplotype analysis supports HLA-C as the psoriasis susceptibility 1 gene. Am J Hum Genet 2006;78(5):827-51.</p><p>Rahman P., Roslin N.M., Pelett FJ. et al. High resolution mapping in the major histocompatibility complex region identifies multiple independent novel loci for psoriatic arthritis. Ann Rheum Dis 2011;70(4):690-4.</p><p>Lopez-Larrea C., Torre Alonso J.C. HLA antigens in psoriatic arthritis subtypes of a Spanish population. Ann Rheum Dis 1990;49(5):318-9.</p><p>Gladman D., Farewell T. The role of HLA antigens as indicators of disease progression in psoriatic arthritis. Arthr Rheum 1995;6:845-50.</p><p>Gladman D.D., Farewell V.T., Nadeau T. et al. HLA markers and progression in psoriatic arthritis. J Rheumatol 1998;25(4):730-3.</p><p>Queiro R., Sarasqueta C. Psoriatic spondyloarthropathy: a comparative study between HLA-B27 positive and HLA-B27 negative disease. Semin Arthr Rheum 2002;31(6):413-8.</p><p>Alenius G.M., Jidell E., Nordmark L. et al. Disease manifestations and HLA antigens in psoriatic arthritis in northern Sweden. Clin Rheumatol 2002;21(5):357-62.</p><p>Sakkas L.I., Loqueman N., Bird H. et al. HLA class II and T cell receptor gene polymorphisms in psoriatic arthritis and psoriasis. J Rheumatol 1990;17(11):1487-90.</p><p>Korendowych E., Dixey J., Cox B. et al. The Influence of the HLA-DRB1 rheumatoid arthritis shared epitope on the clinical characteristics and radiological outcome of psoriatic arthritis. J Rheumatol 2003;30(1):96-101.</p><p>Эрдес Ш.Ф. Клинико-генетическое исследование поражения суставов при псориазе: Автореф. дис.. канд. мед. наук. М., 1987; 21 с.</p><p>Димитрова Д., Минев М., Трюнкова Т. HLA-система у больных псориатическим артритом. Тер aрх 1991;63(5):62-3.</p><p>Fournie B., Granel J., Heraud A. et al. HLA-B and psoriatic rheumatism. Study of 193 cases. Rev Rhum Mal Osteoartic 1991; 58(4):269-73.</p><p>Muto M., Date Y., Ichimiya M. et al. Significance of antibodies to streptococcal M protein in psoriatic arthritis and their association with HLA-A*0207. Tissue Antigens 1996;48(6):645-50.</p><p>Elkayam O., Segal R., Caspi D. et al. Human leukocyte antigen distribution in Israeli patients with psoriatic arthritis. Rheumatol Int 2004;24(2):93-7.</p><p>Grubic Z., Peric P., Cecuk-Jelicic E. et al. The distribution of HLA alleles class I and class II among patientes with psoriatic arthritis in Croatia. Reumatizam 2004;1(1):5-11.</p><p>Imre K, Koo E, Sesztak M. et al. Genetics in patients with psoriatic arthritis. Orv Hetil 2006;147(50):2415-9.</p><p>Liao H.T., Lin K.C., Chang Y.T. et al. Human leukocyte antigen and clinical and demographic characteristics in psoriatic arthritis and psoriasis in Chinese patients. J Rheumatol 2008;35(5):891-5.</p><p>Hohler T., Schneider P.M., Rittner C. et al. LMP polymorphisms do not influence disease expression in psoriatic arthritis. Clin Exp Rheumatol 1996;14(6):661-4.</p><p>Marsal S., Armadans-Gil L., Nartinez M. et al. Clinical, radiographic and HLA associations as markers for different patterns of psoriatic arthritis. Rheumatology (Oxford) 1999;38(4):332-7.</p><p>Salvarani C., Macchioni P.L., Zizzi F. et al. Clinical subgroups and HLA antigens in Italian patients with psoriatic arthritis. Clin Exp Rheumatol 1989;7(4):391-6.</p><p>Яздовский В.В., Воронин А.В., Алексеев Л.П. HLA-генетический профиль русской популяции. Иммунология 1998;2:30-2.</p><p>Агабабова Э.Р., Бадокин В.В., Эрдес Ш.Ф. и др. Разработка и апробация диагностических критериев псориатического артрита. Тер арх 1988;12:117-21.</p><p>Queiro R., Alperi M., Lopez A. et al. Clinical expression, but not disease outcome, may vary according to age at disease onset in psoriatic spondylitis. Joint Bone Spine 2008;75(5):544-7.</p><p>Espinoza L.R., Vasey F.B., Gaylord S.W. et al. Histocompatibility typing in the seronegative spondyloarthropathies: a survey. Semin Arthr Rheum 1982;11:375-81.</p><p>Анищенко М.А., Мельников Б.И., Ярулин Ф.Г. HLA-антигены I класса у больных вульгарным псориазом. Иммунология 1988;3:45-7.</p></div><br />

The authors declare that there are no conflicts of interest present.