Instability of Natural Antibody Repertoires in Systemic Lupus Erythematosus Patients, Revealed by Multiparametric Analysis of Serum Antibody Reactivities

Abstract

Recent views on autoimmune diseases invoke generalized but specific perturbations in antibody repertoires, rather than the clonally restricted or non-specific polyclonal alterations proposed thus far. The present experiments analyse serum antibody reactivities in 24 systemic lupus erythematosus (SLE) patients and 17 healthy controls, using a method that quantitatively scores a large number of antibody reactivities and allows for multiparametric statistical analyses. The results show global but relatively specific perturbations in SLE antibody repertoires, and identify novel disease-associated reactivity patterns. Furthermore, a time series analysis of serum antibodies over 3 months demonstrates instability of natural antibody repertoires in individual SLE patients, contrasting with their remarkable conservation in healthy donors. Moreover, the method used clusters controls and patients independently, and might prove of diagnostic value, once large data bases are established.

Characterization of discriminant human brain antigenic targets in neuropsychiatric systemic lupus erythematosus using an immunoproteomic approach

“…The natural B cell and T cell self-reactive repertoire is now recognized as the determinant for the homeostasis of lymphoid cells and the maintenance of self tolerance (33). Unstable patterns of antibody repertoires, possibly related to the adaptive immune response, have been described in systemic autoimmune diseases such as SLE (35). However, discriminant, stable, self-IgG patterns, probably related to pathogenic events, have been found in organ-specific autoimmune disease such as MS after 1 year of followup (30).…”

Visita à imunologia

“…One of the most interesting is in autoimmune diseases, such as systemic lupus erythematosus 50 , atherosclerosis 51 , systemic sclerosis, and others.…”

The conservative physiology of the immune system

“…There is a fourth important aspect: Panama blots undergo significant and characteristic changes during severe alterations of immunological activities, such as human autoimmune diseases (41)(42)(43). More recently, changes in Panama blot profiles against autologous organs and/or E. coli extracts were correlated with clinical forms of chronic parasitic diseases, such as trypanosomiasis cruzi, malaria and schistosomiasis mansoni, both in humans and in mice (4,5,44).…”

“…Aberrant patterns of connectivity of the immune system are associated with autoimmune diseases, in which significant changes in the pattern of immu-noglobulin formation occur (41)(42)(43). When von Pirquet and Schick characterized serum sickness , they showed that immunological activities, of themselves, are not always defensive and may be damaging to the organism (47).…”

“…The physiology of the immune system is conservative and maintains steady states of lymphocyte activation and differentiation acquired early in ontogenesis, influenced but not determined by maternal and early environmental factors, as revealed by the ontogeny of patterns of natural IgM reactivity with complex antigenic mixtures (40)(41)(42)(43). We propose that clonal expansions occurring during infectious, allergic and autoimmune diseases are elements inherent to the pathology of these conditions, which may be better described as deviations from normal dynamics than as defensive reactions.…”