Anti-rods/rings: a human model of drug-induced autoantibody generation.

S John Calise,Edward K L Chan,Luis E C Andrade,Gerson D Keppeke

doi:10.3389/fimmu.2015.00041

S John Calise, Edward K L Chan + Show 2 more

Open Access

https://doi.org/10.3389/fimmu.2015.00041

Copy DOI

Abstract

In recent years, autoantibodies targeting subcellular structures described as the rods and rings pattern in HEp-2 ANA have been presented as a unique case of autoantibody generation. These rod and ring structures (RR) are at least partially composed of inosine monophosphate dehydrogenase type 2 (IMPDH2), and their formation can be induced in vitro by several small-molecule inhibitors, including some IMPDH2 inhibitors. Autoantibodies targeting these relatively unknown structures have been almost exclusively observed in hepatitis C virus (HCV) patients who have undergone treatment with pegylated interferon-α/ribavirin (IFN/RBV) combination therapy. To date, anti-RR antibodies have not been found in treatment-naïve HCV patients or in patients from any other disease groups, with few reported exceptions. Here, we describe recent advances in characterizing the RR structure and the strong association between anti-RR antibody response and HCV patients treated with IFN/RBV, detailing why anti-RR can be considered a human model of drug-induced autoantibody generation.

Highlights

Autoantibodies targeting rods and rings (RR) have become an intriguing topic of discussion since 2005, when the unique RR pattern was first observed in a standard IIF-HEp-2 assay
Anti-RR antibodies seem to have an additional stipulation that has been reported by several independent laboratories: treatment with interferon-α/ribavirin combination therapy (IFN/RBV) is, with few exceptions out of all patients reported to date, required to observe anti-RR seropositivity; anti-RR antibodies have not been observed in any hepatitis C virus (HCV) patients prior to treatment [2,3,4,5,6]
An additional consideration is that the exclusivity of the association of anti-RR with treated HCV patients suggests a potential for a biological role for the RR structures, since in this initial study, anti-RR were significantly more prevalent in non-responders and relapsers than in patients responding to IFN/RBV therapy

Summary

INTRODUCTION

Autoantibodies targeting rods and rings (RR) have become an intriguing topic of discussion since 2005, when the unique RR pattern was first observed in a standard IIF-HEp-2 assay Patient sera presenting this novel staining pattern were recognized to be hepatitis C virus (HCV) patients treated with the typical pegylated interferon-α/ribavirin combination therapy (IFN/RBV). AUTOANTIGENIC ROD AND RING STRUCTURES In order to properly discuss anti-RR as a human model of autoantibody generation, it is necessary to first present current knowledge of the novel targets of these antibodies, since the process of elucidation of the RR structures has only been ongoing for less than a decade. RR structures present themselves in two major forms, discrete filamentous “rods” 3–10 μm in length or annular “rings” 2–5 μm in diameter (Figure 1) Both forms are observed primarily in the cytoplasm, generally smaller structures are regularly found in the nucleus under cellular conditions allowing for RR formation [5]. The primary target and major component of the RR structures is the enzyme www.frontiersin.org

Acivicin Decoyinine DON Mycophenolic acid Pemetrexed Ribavirin

Findings

CONCLUSION