Öz
Purpose: The aim of this study was to investigate whether C2 polymorphisms influence the symptoms and disease outcomes in children with Henoch Schönlein purpura (HSP).
Materials and Methods: This cross-sectional study included 49 children with HSP, diagnosed and followed for at least 6 months in our department between July 2016 and March 2018. Sanger sequencing was performed for detecting C2 gene polymorphisms. Statistical analysis was performed for comparison of clinical and laboratory parameters between patients according to having C2 polymorphisms.
Results: Only 6 patients (12.2%) had following C2 gene polymorphisms: rs9332739 (n=3), rs36221133 (n=2), rs146054348 (n=1). Age at disease onset, gastrointestinal and joint involvement, serum complement levels, renal involvement, requirement of systemic steroids and disease relapse were found similar between the patients with and without C2 gene polymorphism. We found higher serum IgM level and lower leukocyte counts in HSP patients with confirmed C2 polymorphisms than the patients with normal C2 gene.
Conclusion: Although C2 gene polymorphisms were not related to clinical manifestations and disease outcome in children with HSP, we speculate that C2 gene polymorphisms may be associated with elevated serum IgM levels in patients with HSP.
Anahtar Kelimeler
C2 gene Henoch Schönlein Purpura IgA vasculitis polymorphism
Destekleyen Kurum
Cukurova University Scientific Research Projects Coordination Unit
Proje Numarası
TSA-2018-10124
Teşekkür
This work was supported by the grants from the Cukurova University Scientific Research Projects Coordination Unit (TSA-2018-10124), Adana, Turkey.
Kaynakça
- Eleftheriou D, Dillon MJ, Brogan PA. Advances in childhood vasculitis. Curr Opin Rheumatol. 2009;21:411-8.
- Heineke MH, Ballering AV, Jamin A, Ben Mkaddem S, Monteiro RC, Van Egmond M. New insights in the pathogenesis of immunoglobulin A vasculitis (Henoch-Schönlein purpura). Autoimmun Rev. 2017;16:1246-53.
- Goldstein AR, White RH, Akuse R, Chantler C. Long-term follow-up of childhood Henoch-Schönlein nephritis. Lancet. 1992;339:280-2.
- Chen M, Daha MR, Kallenberg CG. The complement system in systemic autoimmune disease. J Autoimmun. 2010;34:276-86.
- Smith GC, Davidson JE, Hughes DA, Holme E, Beattie TJ. Complement activation in Henoch-Schönlein purpura. Pediatr Nephrol. 1997;11:477-80.
- Lin Q, Min Y, Li Y, Zhu Y, Song X, Xu Q et al. Henoch-Schönlein purpura with hypocomplementemia. Pediatr Nephrol. 2017;27:801-6.
- Vignesh P, Rawat A, Sharma M, Singh S. Complement in autoimmune diseases. Clin Chim Acta. 2017;465:123-30.
- Chen HH, Tsai LJ, Lee KR, Chen YM, Hung WT, Chen DY. Genetic association of complement component 2 polymorphism with systemic lupus erythematosus. Tissue Antigens. 2015;86:122-33.
- Jönsson G, Sjöholm AG, Truedsson L, Bengtsson AA, Braconier JH, Sturfelt G. Rheumatological manifestations, organ damage and autoimmunity in hereditary C2 deficiency. Rheumatology (Oxford). 2007;46:1133-9.
- Mills JA, Michel BA, Bloch DA, Calabrese LH, Hunder GG, Arend WP et al. The American College of Rheumatology 1990 criteria for the classification of Henoch-Schönlein purpura. Arthritis Rheum. 1990;33:1114-21.
- Ozen S, Pistorio A, Iusan SM, Bakkaloglu A, Herlin T, Brik R et al. EULAR/PRINTO/PRES criteria for Henoch-Schönlein purpura, childhood polyarteritis nodosa, childhood Wegener granulomatosis and childhood Takayasu arteritis: Ankara 2008. Part II: Final classification criteria. Ann Rheum Dis. 2010;69:798-806.
- Koskela M, Ylinen E, Ukonmaanaho EM, Autio-Harmainen H, Heikkilä P, Lohi J et al. The ISKDC classification and a new semiquantitative classification for predicting outcomes of Henoch-Schönlein purpura nephritis. Pediatr Nephrol. 2017;32:1201-9.
- Jennette JC. Overview of the 2012 revised International Chapel Hill Consensus Conference nomenclature of vasculitides. Clin Exp Nephrol. 2013;17:603-6.
- Besbas N, Saatci U, Ruacan S, Ozen S, Sungur A, Bakkaloglu A et al. The role of cytokines in Henoch Schonlein purpura. Scand J Rheumatol. 1997;26:456-60.
- Pan YX, Ye Q, Shao WX, Shang SQ, Mao JH, Zhang T et al. Relationship between immune parameters and organ involvement in children with Henoch-Schonlein purpura. PLoS One. 2014;9:e115261.
- 16. Motoyama O, Iitaka K. Henoch-Schonlein purpura with hypocomplementemia in children. Pediatr Int. 2005;47:39-42.
- Krause I, Garty BZ, Davidovits M, Cleper R, Tamary H, Rosenmann E et al. Low serum C3, leukopenia, and thrombocytopenia: unusual features of henoch-schonlein purpura. Eur J Pediatr. 1999;158:906-9.
- He X, Yu C, Zhao P, Ding Y, Liang X, Zhao Y et al. The genetics of Henoch-Schönlein purpura: a systematic review and meta-analysis. Rheumatol Int. 2013;33:1387-95.
- Ekinci RMK, Balci S, Bisgin A, Atmis B, Dogruel D, Altintas DU et al. MEFV gene variants in children with Henoch-Schönlein purpura and association with clinical manifestations: a single-center Mediterranean experience. Postgrad Med. 2019;131:68-72.
- Jin DK, Kohsaka T, Koo JW, Ha IS, Cheong HI, Choi Y. Complement 4 locus II gene deletion and DQA1*0301 gene: genetic risk factors for IgA nephropathy and Henoch-Schönlein nephritis. Nephron. 1996;73:390-5.
- Stefansson Thors V, Kolka R, Edvardsson VO, Edvardsson VO, Arason G, Haraldsson A. Increased frequency of C4B*Q0 alleles in patients with Henoch-Schönlein purpura. Scand J Immunol. 2005;61:274-8.
- Alper CA, Xu J, Cosmopoulos K, Dolinski B, Stein R, Uko G et al. Immunoglobulin deficiencies and susceptibility to infection among homozygotes and heterozygotes for C2 deficiency. J Clin Immunol. 2013;23:297-305.
- Kışla Ekinci RM, Balcı S, Bişgin A, Atmis B, Dogruel D, Yilmaz M. Autoimmune manifestations in heterozygote type I complement 2 deficiency: A child eventually diagnosed with systemic lupus erythematosus. Arch Rheumatol. 2019;34:96-9.
- 24. Lian LH, Ching AS, Chong ZY, Chua KH. Complement components 2 and 7 (C2 and C7) gene polymorphisms are not major risk factors for SLE susceptibility in the Malaysian population. Rheumatol Int. 2012;32:3665-8.
- Hauck F, Lee-kirsch MA, Aust D, Roesler J, Pessler F. Complement C2 deficiency disarranging innate and adaptive humoral immune responses in a pediatric patient: treatment with rituximab. Arthritis Care Res (Hoboken). 2011;63:454-9.
- Weill JC, Weller S, Reynaud CA. Human marginal zone B cells. Annu Rev Immunol. 2009;27:267-85.
Öz
Amaç: Bu çalışmada Henoch Shönlein purpurası (HSP) tanılı çocuklarda C2 gen polimorfizmlerinin semptomlar ve hastalık şiddeti üzerine etkilerinin incelenmesi amaçlanmıştır.
Gereç ve Yöntem: Bu kesitsel çalışmaya kliniğimizde Temmuz 2016 ve Mart 2018 tarihleri arasında HSP tanısı almış ve en az 6 ay takip edilmiş olan 49 çocuk hasta dahil edilmiştir. Kompleman C2 gen polimorfizmlerini değerlendirmek amacı ile Sanger sekanslama tekniği kullanılmıştır. Hastalar C2 gen polimorfizm varlığına gruplara ayrılarak klinik ve laboratuvar verileri karşılaştırılmıştır.
Bulgular: Çalışmamızda sadece 6 (%12,2) hastada C2 gen polimorfizmleri saptanmıştır. Bunlar; rs9332739 (n=3), rs36221133 (n=2), rs146054348 (n=1) olarak sıralanabilir. C2 gen polimorfizmleri varlığına göre hasta grupları arasında yaş, gastrointestinal ve eklem tutulumları, serum kompleman düzeyleri, böbrek tutulumu, sistemik steroid gereksinimi ve hastalık relaps oranları benzer bulunmuştur. C2 gen polimorfizmi olan hastalarda, olmayanlara göre istatistiksel anlamlı olarak daha yüksek serum IgM düzeyi ve daha düşük lökosit sayısı saptanmıştır.
Sonuç: Konusunda ilk olan çalışmamızda her ne kadar C2 gen polimorfizmlerinin HSP’li hastalarda klinik bulgular ve hastalık seyri üzerine etkisi gösterilememiş olsa da, HSP tanılı hastalarda yüksek serum IgM düzeyi C2 gen polimorfizmi ile ilişkili olabilir.
Anahtar Kelimeler
C2 geni Henoch Schönlein Purpurası IgA vasküliti polimorfizm
Proje Numarası
TSA-2018-10124
Kaynakça
- Eleftheriou D, Dillon MJ, Brogan PA. Advances in childhood vasculitis. Curr Opin Rheumatol. 2009;21:411-8.
- Heineke MH, Ballering AV, Jamin A, Ben Mkaddem S, Monteiro RC, Van Egmond M. New insights in the pathogenesis of immunoglobulin A vasculitis (Henoch-Schönlein purpura). Autoimmun Rev. 2017;16:1246-53.
- Goldstein AR, White RH, Akuse R, Chantler C. Long-term follow-up of childhood Henoch-Schönlein nephritis. Lancet. 1992;339:280-2.
- Chen M, Daha MR, Kallenberg CG. The complement system in systemic autoimmune disease. J Autoimmun. 2010;34:276-86.
- Smith GC, Davidson JE, Hughes DA, Holme E, Beattie TJ. Complement activation in Henoch-Schönlein purpura. Pediatr Nephrol. 1997;11:477-80.
- Lin Q, Min Y, Li Y, Zhu Y, Song X, Xu Q et al. Henoch-Schönlein purpura with hypocomplementemia. Pediatr Nephrol. 2017;27:801-6.
- Vignesh P, Rawat A, Sharma M, Singh S. Complement in autoimmune diseases. Clin Chim Acta. 2017;465:123-30.
- Chen HH, Tsai LJ, Lee KR, Chen YM, Hung WT, Chen DY. Genetic association of complement component 2 polymorphism with systemic lupus erythematosus. Tissue Antigens. 2015;86:122-33.
- Jönsson G, Sjöholm AG, Truedsson L, Bengtsson AA, Braconier JH, Sturfelt G. Rheumatological manifestations, organ damage and autoimmunity in hereditary C2 deficiency. Rheumatology (Oxford). 2007;46:1133-9.
- Mills JA, Michel BA, Bloch DA, Calabrese LH, Hunder GG, Arend WP et al. The American College of Rheumatology 1990 criteria for the classification of Henoch-Schönlein purpura. Arthritis Rheum. 1990;33:1114-21.
- Ozen S, Pistorio A, Iusan SM, Bakkaloglu A, Herlin T, Brik R et al. EULAR/PRINTO/PRES criteria for Henoch-Schönlein purpura, childhood polyarteritis nodosa, childhood Wegener granulomatosis and childhood Takayasu arteritis: Ankara 2008. Part II: Final classification criteria. Ann Rheum Dis. 2010;69:798-806.
- Koskela M, Ylinen E, Ukonmaanaho EM, Autio-Harmainen H, Heikkilä P, Lohi J et al. The ISKDC classification and a new semiquantitative classification for predicting outcomes of Henoch-Schönlein purpura nephritis. Pediatr Nephrol. 2017;32:1201-9.
- Jennette JC. Overview of the 2012 revised International Chapel Hill Consensus Conference nomenclature of vasculitides. Clin Exp Nephrol. 2013;17:603-6.
- Besbas N, Saatci U, Ruacan S, Ozen S, Sungur A, Bakkaloglu A et al. The role of cytokines in Henoch Schonlein purpura. Scand J Rheumatol. 1997;26:456-60.
- Pan YX, Ye Q, Shao WX, Shang SQ, Mao JH, Zhang T et al. Relationship between immune parameters and organ involvement in children with Henoch-Schonlein purpura. PLoS One. 2014;9:e115261.
- 16. Motoyama O, Iitaka K. Henoch-Schonlein purpura with hypocomplementemia in children. Pediatr Int. 2005;47:39-42.
- Krause I, Garty BZ, Davidovits M, Cleper R, Tamary H, Rosenmann E et al. Low serum C3, leukopenia, and thrombocytopenia: unusual features of henoch-schonlein purpura. Eur J Pediatr. 1999;158:906-9.
- He X, Yu C, Zhao P, Ding Y, Liang X, Zhao Y et al. The genetics of Henoch-Schönlein purpura: a systematic review and meta-analysis. Rheumatol Int. 2013;33:1387-95.
- Ekinci RMK, Balci S, Bisgin A, Atmis B, Dogruel D, Altintas DU et al. MEFV gene variants in children with Henoch-Schönlein purpura and association with clinical manifestations: a single-center Mediterranean experience. Postgrad Med. 2019;131:68-72.
- Jin DK, Kohsaka T, Koo JW, Ha IS, Cheong HI, Choi Y. Complement 4 locus II gene deletion and DQA1*0301 gene: genetic risk factors for IgA nephropathy and Henoch-Schönlein nephritis. Nephron. 1996;73:390-5.
- Stefansson Thors V, Kolka R, Edvardsson VO, Edvardsson VO, Arason G, Haraldsson A. Increased frequency of C4B*Q0 alleles in patients with Henoch-Schönlein purpura. Scand J Immunol. 2005;61:274-8.
- Alper CA, Xu J, Cosmopoulos K, Dolinski B, Stein R, Uko G et al. Immunoglobulin deficiencies and susceptibility to infection among homozygotes and heterozygotes for C2 deficiency. J Clin Immunol. 2013;23:297-305.
- Kışla Ekinci RM, Balcı S, Bişgin A, Atmis B, Dogruel D, Yilmaz M. Autoimmune manifestations in heterozygote type I complement 2 deficiency: A child eventually diagnosed with systemic lupus erythematosus. Arch Rheumatol. 2019;34:96-9.
- 24. Lian LH, Ching AS, Chong ZY, Chua KH. Complement components 2 and 7 (C2 and C7) gene polymorphisms are not major risk factors for SLE susceptibility in the Malaysian population. Rheumatol Int. 2012;32:3665-8.
- Hauck F, Lee-kirsch MA, Aust D, Roesler J, Pessler F. Complement C2 deficiency disarranging innate and adaptive humoral immune responses in a pediatric patient: treatment with rituximab. Arthritis Care Res (Hoboken). 2011;63:454-9.
- Weill JC, Weller S, Reynaud CA. Human marginal zone B cells. Annu Rev Immunol. 2009;27:267-85.
Ayrıntılar
| Birincil Dil | İngilizce |
|---|---|
| Konular | Çocuk Sağlığı ve Hastalıkları |
| Bölüm | Araştırma |
| Yazarlar | |
| Proje Numarası | TSA-2018-10124 |
| Yayımlanma Tarihi | 31 Mart 2020 |
| Kabul Tarihi | 22 Kasım 2019 |
| Yayımlandığı Sayı | Yıl 2020 Cilt: 45 Sayı: 1 |
