Identification of clinically relevant cytomegalovirus infections in patients with inflammatory bowel disease

Abstract

Several lines of evidence indicate that cytomegalovirus infection can be substantially associated with onset of inflammatory bowel disease, especially in patients refractory to immunosuppressive treatment. As cytomegalovirus is widely spread in the population, here we present a quantitative detection system suitable to differentiate clinically relevant cytomegalovirus infection from common latent cytomegalovirus. Using a quantitative real-time PCR approach, cytomegalovirus viral load was evaluated in 917 formalin-fixed and paraffin-embedded colon biopsy samples of 136 patients diagnosed with inflammatory bowel disease. Besides initial cytomegalovirus testing, the PCR system was also used to monitor therapy response after antiviral treatment. Cytomegalovirus DNA was detected in 37 patients (27%) with varying viral loads ranging from 5 to 8.7 × 10 copies/10 cells. Thereof, 13 patients (35%) received an antiviral treatment with 12 of them going into remission (92%). Later, five patients displayed a relapse and three patients who agreed to restart antiviral treatment again showed positive therapy response. A retrospective comparison of viral loads with antiviral therapy response revealed a threshold of 600 cytomegalovirus copies/10 cells as indicative for clinically relevant infection. Of note, sensitivity of cytomegalovirus detection by immunohistochemistry was found to be insufficient to reliably identify antiviral therapy responders. In conclusion, quantitative real-time PCR using formalin-fixed biopsy samples is suitable for detection of cytomegalovirus infection in tissue samples of patients with inflammatory bowel disease. Moreover, it allows the definition of a viral load threshold, predictive for clinical relevance concerning antiviral therapy response.

Cytomegalovirus reactivation in inflammatory bowel disease: an uncommon occurrence related to corticosteroid dependence

“…Serologic studies are of limited value because they do not always distinguish remote viral exposure from active infection. Assays that detect cytomegalovirus DNA by PCR are frequently performed to detect symptomatic cytomegalovirus infection but do not necessarily correlate with the abundance of inclusions detected in mucosal samples [22].…”

Perspectives of cytomegalovirus infection in ulcerative colitis

“…As the rectal region is more prone to the infection and usually shows the most severe inflammation in UC, CMV may be more likely to be accumulated at this site. 34 The ulcer bed seems to be the reservoir of CMV 35,36 ; however, this area cannot be accessed due to the risk of bleeding and intestinal perforation. To improve the sensitivity of histologic examination, an immunohistochemical study has been used, and this combination is considered the gold standard for the detection of CMV.…”

İnflamatuvar Bağırsak Hastalığı Olan Çocuklarda Sitomegalovirüs ve Epstein-Barr Virüs Enfeksiyonlarının Sıklığı ve Önemi: Tek Merkez Deneyimi

“…CMV DNA ve EBV DNA gerçek zamanlı polimeraz zincir reaksiyonu (RT-PCR) (Qiagen, Almanya) ile incelendi. Eşlik eden kolit bulguları ile birlikte serumda CMV DNA'nın > 600 kopya/mL üzerinde, EBV DNA >150 kopya/mL olması klinik anlamlı olarak kabul edildi (4). EBV için klinik anlamlılık laboratuvar referans değerine göre belirlendi.…”

“…Özellikle popülasyonda yaygın olarak bulunan sitomegalovirüs (CMV) ve Epstein-Barr virüs (EBV) hedef hücrelerde latent kalma özellikleri nedeniyle immünsüprese hastalarda reaktivasyonlarla seyredebilmektedir. Bu nedenle İBH hastalarında önemli sorun oluşturabilmektedirler (4,5). Yapılan çalışmalarda CMV veya EBV DNA'nın düşük titrede pozitifliğinin hastaların tedaviye direncinde rol oynadığını belirtilmektedir (6).…”

“…Bu nedenle, bu hasta grubunda CMV enfeksiyonlarına hızlı ve doğru tanı konulması kritiktir. Bu hastalarda immünsüpresif tedaviye ek olarak malnütrisyonun da neden olduğu natural killer (NK) T hücre fonksiyonlarında da yetersizlik görülebilmektedir (4). Çalışmamızda hem tanı sırasında hem de atak dönemlerinde CMV ve EBV gibi hedef hücrelerde latent kalan virüslerin sıklığı, yaptığı laboratuvar ve klinik değişikliklerin analiz edilmesi ve klinik sonuç üzerine etkileri belirlenmeye çalışılmıştır.…”