Antibodies to Rods and Rings

Rods and rings (RR) are distinct cytoplasmic structures known to be composed of at least two enzymes critical for pyrimidine and purine synthesis. Due to the considerable size of these rods (3-10 μm in length) and rings (2-5 μm in diameter), RR are likely comprised of other unidentified proteins that may be related to nucleotide metabolism. Inhibition of either of the two known enzymes, cytidine triphosphate synthase 1 (CTPS1) and inosine monophosphate dehydrogenase 2 (IMPDH2), induces formation of RR in all cell lines examined to date. Therefore, the function of RR is affiliated with nucleotide metabolism since RR have been found to form under conditions of increased intracellular cytidine triphosphate (CTP) and guanosine triphosphate (GTP) requirements, such as in highly metabolically active cells like embryonic stem cells. Autoantibodies to RR have been identified in hepatitis C virus (HCV) patients who have undergone treatment with pegylated interferon-α/ribavirin therapy (IFN/R), but not detected in untreated chronic HCV patients. Our data show that HCV patients with high titer anti-RR are more likely to be nonresponders or relapsers to IFN/R therapy.