ABSTRAK
Latar belakang: Karbamazepin KBZ merupakan obat terpilih untuk epilepsi fokaldan dapat digunakan juga untuk pengobatan nyeri neuropatik dan gangguan bipolar,namun dapat menyebabkan reaksi obat yang berat berupa sindrom Stevens-Johnson SSJ /nekrolisis epidermal toksik NET . Saat ini banyak penelitian yangmembuktikan terdapat hubungan antara HLA-B 1502 dengan SSJ/NET yangdisebabkan oleh KBZ pada orang Asia.Tujuan: Meneliti apakah HLA-B 1502 dapat dijadikan marker terjadinya SSJ/NETyang disebabkan oleh KBZ di Indonesia.Metode: Subjek penelitian direkrut dari poliklinik saraf RSUPN CiptoMangunkusumo Jakarta, RS Hasan Sadikin Bandung 2 kasus dan RSUP Prof RDKandou Manado 2 kasus pada Mei 2015 sampai dengan Desember 2016. Subjekdengan riwayat SSJ/NET yang disebabkan KBZ dan toleran KBZ dilakukanpemeriksaan typing HLA-B dengan metode sequence specific oligonucleotidesprobes, dibaca dengan Luminex 200 dan dianalisis dengan perangkat lunak HLAfushion4.0. Dipilih beberapa subjek SSJ/NET dengan HLA-B 1502 positif dannegatif dan toleran dengan HLA-B 1502 positif dan negatif. Subjek yang dipilih inidilakukan kultur PBMC dengan perlakuan penambahan KBZ dan tanpa perlakuanselama 24 dan 48 jam, kemudian diukur kadar granulisin, granzim B dan perforindalam medium kultur dengan metode ELISA, untuk melihat peranan HLA-B 1502dalam terjadinya SJS/NET.Hasil: Total subjek 67 orang, 14 kasus dan 53 toleran. Pada semua subjek dilakukantyping HLA-B, sedangkan kultur dan pemeriksaan kadar granulisin, granzim B danperforin dilakukan pada 17 subjek 6 SSJ/NET dengan HLA-B 1502 positif dan 3negatif; 5 toleran HLA-B 1502 positif dan 3 negatif HLA-B 1502 positifditemukan pada 8 kasus 57,14 dan 14 toleran 26,42 , dengan rasio prevalensi2,73 dan p= 0,0353. Terdapat kecenderungan lonjakan kadar granulisin padakelompok subjek dengan SSJ/NET dibandingkan kelompok toleran KBZ.Kesimpulan: HLA-B 1502 dapat digunakan sebagai marker pada SSJ/NET karenaKBZ.Kata Kunci: HLA-B 1502, KBZ, SJS/NET, Indonesia
ABSTRACT
Background Carbamazepine CBZ is a drug of choice for focal epilepsy and canbe used for neuropatic pain and bipolar disorder, but it can also causes severe drugreaction in the form of Stevens Johnson Syndrome SJS toxic epidermal necrolysis TEN . Currently, there are many studies that prove the relationship between HLAB 1502and SJS TEN caused by CBZ in Asian ancestry.Objective To study whether HLA B 1502 can be used as marker for SJS TENcaused by CBZ in Indonesia.Method Subjects were recruited from neurology clinic RSUPN CiptoMangunkusumo, RS Hasan Sadikin Bandung two cases , and RSUP Prof. RDKandou Manado two cases , from May 2015 to December 2016. Subjectswith SJS TEN history caused by CBZ and CBZ tolerant went through HLA Btyping examination with sequence specific oligonucleotides probes method, readwith Luminex 200 and analyzed with HLA fusion 4.0 software. Some subjectswith SJS TEN with HLA B 1502 positive and negative, and tolerant subjects withHLA B 1502 positive and negative, were chosen. These subjects went throughPBMC culture with and without CBZ addition for 24 and 48 hours, then granulysin,granzyme B and perforin concentration in culture medium were measured usingELISA method to see the role of HLA B 1502 in SJS TEN occurrence.Result Total number of subjects were 67 with, 14 CBZ induced SJS NET cases and53 CBZ tolerants. All subjects went through HLA typing, while culture andgranulysin, granzyme B and perforin examination were conducted in 17 subjects 6with SJS TEN with HLA B 1502 positive and 3 negative 5 tolerant HLA B 1502positive and 3 negative . HLA B 1502 positive were found in 8 cases 57,14 and14 tolerant 26,42 , with prevalence ratio 2,73 p 0,035. There is a tendencyincreased of granulysin level in CBZ induced SSJ NET cases.Conclusion HLA B 1502 can be used as marker in SJS TEN induced by CBZ. |
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