POS-053 Type I Beta Interferon induced thrombotic microangiopathy – Could the alternative pathway of the complement be implicated?

IntroductionThrombotic microangiopathy (TMA) is a rare systemic microvascular disorder characterized by microangiopathic hemolytic anemia, thrombocytopenia, and ischemic damage in different organs. Beta-interferon (β-IFN), an immune-modulating agent widely used as first line treatment for relapsing–remitting multiple sclerosis (RRMS), has been associated with TMA several reports but the underlying mechanisms are still controversial. Treatment mainly based on plasma exchanges, corticosteroids renal prognosis poor.MethodsWe report case of 48-year-old male patient, 13-years history RRMS, treated weekly 132 µg type I Beta-Interferon (βI-IFN) admitted focal seizure. Initial investigations revealed classical laboratory features severe acute kidney injury requiring replacement therapy. Renal biopsy was performed showed lesions. Thrombotic thrombocytopenic purpura typical uremic syndrome were ruled out. Laboratory findings interestingly suggested possible involvement alternative pathway complement (APC) CFB: 32,5 mg/dl (normal value: 11-22 mg/dl), FBb: 0,258 value <0,153 mg/dl) SC5b-9: 822 ng/ml <314 ng/ml). Genetic workup did not find mutation regulators APC, search anti-factor H antibodies negative. The withdrawal βI-IFN resulted rapid resolution anemia delayed improvement function. No exchange required no eculizumab administered because absence reimbursement procedure available our country secondary TMA.ResultsTMA complication treatment. Recent experimental data suggest causal relationship. Kavanagh et al. that responsible direct dose-dependent rodent model, absent I-IFN receptor (IFNAR) knock-out mice. Jia could interfere endothelial cell inhibiting fibrinolysis VEGF-dependent angiogenesis. Furthermore, eculizumab, anti-C5 antibody blocking terminal activation, reported to significantly improve series even APC. These 1) may occur second hit patients yet undiscovered mutations APC; or 2) IFN activate cascade without Indeed, some activation type-I IFN, indirect link can also be hypothesized. For example, antiphospholipid have known TMA. Figure 1. summarizes pathophysiological hypotheses mediated Blue lines represent from literature, whereas green arrows hypotheses. red arrow represents lacking up now.ConclusionsβI-IFN well-known complication. toxic effect cells act trigger setting APC regulation deficiency. Eculizumab seems effective, suggesting potential IFN.No conflict interest poor. MethodsWe We ResultsTMA now. ConclusionsβI-IFN IFN.