Psoriasiste anti-TNF ajanlarla tedaviye yanıtta TNF-alfa gen polimorfizmlerinin biyomarker olarak rolü
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Date
2017
Authors
Günay, Berrin
Journal Title
Journal ISSN
Volume Title
Publisher
Uludağ Üniversitesi
Abstract
Psoriasis, eritemli, skuamlı plaklar ile karakterize, multisistemik, Th1 ve Th17 hücre aracılı enflamatuvar bir hastalıktır. Sistemik konvansiyonel tedavilere yanıtsızlık veya kontrendikasyon varlığında anti-TNF (Tümör nekrozis faktör) ajanlar kullanılmaktadır. Anti-TNF ajanlar hastalık kontrolünde efektif bir tedavi yöntemi olmasına rağmen direnç gelişimi önemli bir sorundur. Bu çalışmada psoriasis hastalarında anti-TNF ajanlara yanıt ile TNF-α gen polimorfizmleri arasındaki ilişki araştırılmıştır. Klinik ve histopatolojik olarak psoriasis tanısı almış ve en az bir yıl süreyle anti-TNF ajan tedavisi alan 157 olguda, TNF- 238G>A, -308G>A, -857C>T, -1031T>C gen polimorfizmlerinin, anti-TNF ajanlara primer ve/veya sekonder direnç gelişimi ile ilişkisi değerlendirildi. Genotip tayini için "Polymerase chain reaction-restriction fragment length polymorphism" (PCR-RFLP) yöntemi uygulandı. Çalışmamızda, 22/157 hastada bu ajanlardan en az birine karşı primer direnç mevcuttu. Primer direnç gelişimiyle TNF-α 238G>A, -308G>A, -857C>T, -1031T>C polimorfizmleri arasında herhangi bir ilişki saptanmadı. Sekonder direnç göz önünde bulundurulduğunda, 62 hastada (%39.5) herhangi bir ajana karşı direnç gelişimi saptanmazken, 95 hastada (%60.5) en az bir ajana karşı primer ve/veya sekonder direnç saptandı. Direnç gelişimi ile TNF-α 857C>T ve 1031T>C polimorfizmleri arasında herhangi bir ilişki yoktu. TNF-α 238 AA ve TNF-α 308 AA genotipleri, GA ve GG genotiplerine göre daha düşük direnç gelişimi oranlarıyla ilişkili bulundu. (sırasıyla %16.7 vs %85.7 ve %60.3, p=0.013; %0 vs %63.0 ve %57.7, p=0.43). Adalimumab kullananlarda; TNF-α 238 GA genotipi, AA ve GG genotiplerine göre daha yüksek sekonder direnç oranlarıyla ilişkili bulundu (%69.2 vs %0 ve %40.7; p=0.035). Bulgularımız, spesifik gen polimorfizmlerinin tedaviye sekonder direnç gelişimini öngörmede rolü olabileceğini gösterse de; sonuçlarımızın, geniş serili çalışmalarla desteklenmesine ihtiyaç vardır.
Psoriasis is a multisystemic, Th1 and Th17 cell-mediated inflammatory disease, characterized by erythematous, squamous plaques. Anti-TNF agents are used in the presence of unresponsiveness to conventional therapies or any contraindication. Anti-TNF agents represent an effective treatment modality to control the disease, however, treatment resistance remains a significant issue. In the current study, we aimed to evaluate the relationship between the response to anti-TNF agents in psoriasis patients and the TNF-α gene polymorphisms. In 157 cases of the study, who were clinically and histopathologically diagnosed with psoriasis and received anti-TNF therapy for at least one year, the relationship between TNF- 238G>A, -308G>A, -857C>T, -1031T>C gene polymorphisms and the primary and/or secondary non-response to anti-TNF agents was investigated. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to determine the genotype. In this study, 22 of 157 patients had primary resistance to at least one of these agents. No relationship between primary non-response and TNF-α 238G>A, -308G>A, -857C>T, -1031T>C polymorphisms was found. Considering secondary non-response, 62 patients (39.5%) had no resistance to any of the agents, while 95 patients (60.5%) had primary and/or secondary non-response to at least one agent. There was no relation between non-responsiveness and TNF-α 857C>T and 1031T>C polymorphisms. The genotypes of TNF-α 238 AA and TNF-α 308 AA were found to be associated with lower rates of non-response, comparing to the genotypes of GA and GG (16.7% vs 85.7% and 60.3%, p=0.013; 0% vs 63.0% and 57.7%, p=0.43, respectively). TNF-α 238 GA genotype was found to be associated with higher rates of secondary non-response, comparing to the genotypes of AA and GG in patients who were receiving adalimumab (69.2% vs 0% and 40.7%; p=0.035). Although the results of the current study show that specific gene polymorphisms may play a role in predicting the secondary non-response to therapy, these results are needed to be supported by further large series.
Psoriasis is a multisystemic, Th1 and Th17 cell-mediated inflammatory disease, characterized by erythematous, squamous plaques. Anti-TNF agents are used in the presence of unresponsiveness to conventional therapies or any contraindication. Anti-TNF agents represent an effective treatment modality to control the disease, however, treatment resistance remains a significant issue. In the current study, we aimed to evaluate the relationship between the response to anti-TNF agents in psoriasis patients and the TNF-α gene polymorphisms. In 157 cases of the study, who were clinically and histopathologically diagnosed with psoriasis and received anti-TNF therapy for at least one year, the relationship between TNF- 238G>A, -308G>A, -857C>T, -1031T>C gene polymorphisms and the primary and/or secondary non-response to anti-TNF agents was investigated. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to determine the genotype. In this study, 22 of 157 patients had primary resistance to at least one of these agents. No relationship between primary non-response and TNF-α 238G>A, -308G>A, -857C>T, -1031T>C polymorphisms was found. Considering secondary non-response, 62 patients (39.5%) had no resistance to any of the agents, while 95 patients (60.5%) had primary and/or secondary non-response to at least one agent. There was no relation between non-responsiveness and TNF-α 857C>T and 1031T>C polymorphisms. The genotypes of TNF-α 238 AA and TNF-α 308 AA were found to be associated with lower rates of non-response, comparing to the genotypes of GA and GG (16.7% vs 85.7% and 60.3%, p=0.013; 0% vs 63.0% and 57.7%, p=0.43, respectively). TNF-α 238 GA genotype was found to be associated with higher rates of secondary non-response, comparing to the genotypes of AA and GG in patients who were receiving adalimumab (69.2% vs 0% and 40.7%; p=0.035). Although the results of the current study show that specific gene polymorphisms may play a role in predicting the secondary non-response to therapy, these results are needed to be supported by further large series.
Description
Keywords
Psoriasis, Polimorfizm, TNF-α, Anti-TNF ajanlar, Polymorphisims, Anti-TNF agents
Citation
Günay, B. (2017). Psoriasiste anti-TNF ajanlarla tedaviye yanıtta TNF-alfa gen polimorfizmlerinin biyomarker olarak rolü. Yayınlanmamış uzmanlık tezi. Uludağ Üniversitesi Tıp Fakültesi.