Cytoplasmic Rods and Rings Autoantibodies Developed during Pegylated Interferon and Ribavirin Therapy in Patients with Chronic Hepatitis C

Abstract

An RBV-induced autoantibody was identified to a new cytoplasmic autoantigenic structure developed in HCV patients after PEG-IFN/RBV and this same structure can be induced by RBV in in vitro culture. Owing to the onset of anti-RR antibodies in PEG-IFN/RBV-treated patients and their association with a treatment failure, studies are deemed necessary to clarify whether anti-RR plays a role in the response to PEG-IFN/RBV therapy.

Assembly of IMPDH2-Based, CTPS-Based, and Mixed Rod/Ring Structures Is Dependent on Cell Type and Conditions of Induction

“…Reports have shown the presence of anti-RR autoantibodies in up to 70% of HCV patients under interferon-a plus ribavirin treatment (Seelig et al, 2011;Covini et al, 2012;Keppeke et al, 2012). Stinton et al (2013), using an addressable laser bead immunoassay with beads conjugated to IMPDH2 and CTPS1 enzymes, found that only one out of ten anti-RR-positive serum samples had antibodies to IMPDH2 and none reacted with CTPS1.…”

“…Anti-RR positive sera from HCV patients recognized only IMPDH2-based RR structures HCV patients that have undergone ribavirin/interferon-a therapy develop autoantibodies that recognize RR structures in a standard ANA-HEp-2 test (Covini et al, 2012;Keppeke et al, 2012;Carcamo et al, 2013;Stinton et al, 2013;Novembrino et al, 2014). It has been consistently shown that these autoantibodies recognize the IMPDH2 enzyme in roughly 70% of anti-RR positive samples (Seelig et RR components remains unknown.…”

“…Ribavirin is used as an adjuvant to interferon-a therapy in chronic hepatitis C virus (HCV) infection. Curiously, it has been shown that 20%-40% of HCV patients treated with interferon-a plus ribavirin present autoantibodies against RR structures after six months of treatment, with titers increasing throughout treatment and eventually decreasing after interruption of treatment (Covini et al, 2012;Keppeke et al, 2012;Novembrino et al, 2014). These autoantibodies seem to be, in most cases, directed against IMPDH2, which is the very target of ribavirin used in the anti-HCV treatment (Carcamo et al, 2011(Carcamo et al, , 2013Seelig et al, 2011;Probst et al, 2013).…”

Report on the second International Consensus on ANA Pattern (ICAP) workshop in Dresden 2015

“…The nuclear dense fine speckled pattern (AC-2) is considered particularly important given its strong association with anti-DFS70/LEDGF antibodies and the fact that many investigators either have not heard of it or do not know the relevance of its negative correlation to systemic autoimmune rheumatic diseases. 8,9 There was some concern over the apparent lack of clinical relevance of Golgi-like pattern (AC-22) [10][11][12] or the rods and rings pattern (AC-23), [13][14][15][16] and yet they represent distinctive and consistent patterns that belong to the competentlevel group. It has been proposed that the competent level and expert level are equivalent to the more simple description of ''basic'' and ''advanced'' levels and should not depend strictly on the clinical relevance of the pattern.…”

Loukoumasomes Are Distinct Subcellular Structures from Rods and Rings and Are Structurally Associated with MAP2 and the Nuclear Envelope in Retinal Cells

“…These structures are found predominantly in the cytoplasm, although smaller versions have been found in the nucleus [5] (for review see [3]). The enzyme inosine monophosphate dehydrogenase (IMPDH) is a major component of RR [1, 4, 6–8] and functions primarily in the GTP biosynthesis pathway by catalyzing the rate-limiting conversion of inosine monophosphate into xanthosine monophosphate. Two isotypes of IMPDH, IMPDH1 and IMPDH2, are ubiquitously expressed in mammals, with 84% amino acid identities [9–12].…”