Challenges and Controversies in Autoantibodies Associated with Systemic Rheumatic Diseases

Abstract

Since the first identification of self-reactive antibodies in systemic lupus erythematosus and other systemic autoimmune rheumatic diseases, many autoantibodies have been identified as useful probes in molecular and cell biology and as diagnostic and prognostic biomarkers in clinical immunology. Among the autoantigens, double-stranded desoxoribonucleic acid (dsDNA), the Smith antigen (Sm), ribonucleoproteins (RNP), Scl-70 (topoisomerase I), proliferating cell nuclear antigen (PCNA), and others were described as serologic hallmarks in the diagnosis of systemic autoimmune rheumatic diseases. Despite these advances in identifying autoantibody markers, a number of challenges and controversies persist concerning their origin, clinical usefulness and relevance. These include the association between anti-ribosomal P antibodies and clinical features in systemic lupus erythematosus, the disease specificity of several autoantibodies (i.e. chromatin, Jo-1, alpha-fodrin, topo I and CENP), the relationship between the SS-A/Ro52 and SS-A/Ro60 autoantibody system(s) and the detection of anti-RNP/Sm and anti-fibrillarin antibodies.

Multi-center evaluation of autoantibodies to the major ribosomal P C22 epitope

“…Standardization of autoantibody tests and method of choice for the detection of anti-Rib-P antibodies Today, a variety of assay platforms are available for the detection of anti-Rib-P antibodies including LIA, ELISA and ALBIA [6,9,19,21,36,37]. The antigens used in those tests range from short synthetic peptides and recombinant proteins to affinity-purified macromolecular complexes.…”

“…Furthermore, clinical correlations with lupus nephritis [7] or hepatitis [8] have been described, although these findings have not been uniformly observed in all studies and thus are still debated [9]. Evidence for a pathogenic role of anti-Rib-P aabs continues to mount.…”

“…Evidence for a pathogenic role of anti-Rib-P aabs continues to mount. For example, while the correlation of anti-Rib-P aabs with central nerve system (CNS) involvement and psychosis has been under constant discussion [1,6,[9][10][11][12], just recently Katzav and co-workers reported the induction of autoimmune depression in mice by anti-ribosomal aabs [13]. In addition, Matus and colleagues [14] used human anti-Rib-P antibodies affinity-purified via an 11mer peptide derived from the C-terminal part of the cognate protein to demonstrate cross-reactivity with a new neuronal surface P antigen (NSPA).…”

“…Although several studies have analyzed the prevalence and clinical associations of anti-Rib-P antibodies in SLE, there is a pressing need for further investigations since a clear consensus has yet to be achieved [9]. Therefore, the aim of the present study was to evaluate the prevalence of aabs to the major Rib-P (C22) antigen in SLE patient sera and various controls by employing an international, multicenter approach and to shed more light on the reported association between anti-C22 aabs and clinical features in patients with SLE.…”

B cells undergo unique compartmentalized redistribution in multiple sclerosis

“…Although previous studies have demonstrated that CSF samples from patients with active RRMS (aRRMS) are enriched in memory BC and that persisting plasma blasts (PB) are a major source of antibody secreting cells (ASC) during and beyond phases of disease activity there is limited knowledge as to the distribution of distinct BC-subtypes among peripheral and CSF immune cells and how they relate to disease activity or change composition during immunomodulatory treatment [4,5]. Furthermore, it is unknown whether MS is associated with changes in peripheral BC-homeostasis as described for several collagen vascular disorders which share the production of auto-antibodies as a common immune abnormality [9]. In healthy adults the peripheral BC-compartment comprises 60e70% IgD þ CD27 À naïve and 30e40% memory BC, which further divide into IgD À CD27 þ class-switched (CSM-BC), IgD þ CD27 þ unswitched (USM-BC), and a minor portion of IgD À CD27 À doublenegative (DNM-BC) memory BC [10].…”