The Impact of Cytomegalovirus (CMV) Reactivation on Clinical Course and Immunomodulatory Effect in Children with Immune-Thrombocytopenia (ITP)

Background: ITP might be preceded by silent or overt viral infections. CMV, a human herpes virus has high prevalence of infection and an established antiviral protocol; it might trigger ITP and might play a central role in its pathogenesis whether in newly developed ITP or if CMV is not cleared might continue to trigger immune-modulation

Aim: To assess the effect of CMV infection on the course of ITP and to evaluate the effect of CMV positivity on the INF γ and its impact on bleeding scores and outcome in patients with ITP.

Methods: A cross sectional study over 6 months included 68 patients with ITP aged 2-16 years at different time check-points in a ratio almost 1:1:2; (15 patients with newly diagnosed ITP, 16 persistent ITP and 37 chronic course ). Bleeding assessment tool (SMOG score), organomegaly/lymphadenopathy and treatment protocol, its response. All were CMV Ig-G positive. All secondary ITP cases were excluded on basis of clinical and necessary work-up. Interferon Gamma (INF gamma) assay was done by flowcytometry on CD3+ T cells post stimulation in culture media by PMA. CMV serology was measured by enzyme-linked immunosorbent assay with CMV IgM, IgG avidity index. A control group was used for IFN-γ level.

Results: Median age was 4 years for newly diagnosed/persistent ITP (females 48%) and 10 years for chronic ITP ( females 63%). the frequency of CMV IgM positive was 22.6% for new/persistent ITP and 35.1% of pediatrics patients with chronic ITP. All CMV IgM positive patients showed high CMV IgG avidity. INF gamma expression was higher for new and persistent ITP 53.1 ± 16.9 compared to chronic ITP 40.8 ± 11.5, and both were significantly higher than control group 5.3 ± 5.0 (P<0.001). There was negative correlation between INF gamma and HCMV IgG avidity. CMV IgM positive cases did not differ from IgM negative cases according to age, gender, history of preceeding viral illness, clinical presentation, SMOG score, blood picture and platelet count at the time of diagnosis. Response to initial treatment was similar in both HCMV IgM positive patients and CMV IgM negative patients (p=0.466). However, duration of response to first line treatment was longer in patients with CMV IgM negative compared to IgM positive (P=0.04). The differences in response to current treatment were not statistically significant (P=0.39). Conclusion: CMV reactivation is not uncommon in children with ITP especially in chronic course, it might play a role in duration of initial response to immunomodulatory treatment. However, It didn't seem to have an appreciable impact on the clinical severity. In addition, significant high level of IFN gamma is a appreciable findings in all groups of ITP.

Elalfy MS¹, Nugent D Viruses, anti-viral therapy, and viral vaccines in children with immune thrombocytopenia. Semin Hematol. 2016 Apr;53 Suppl 1:S70-2.