Autoantibodies in SLE: Specificities, Isotypes and Receptors

Abstract

Systemic Lupus Erythematosus (SLE) is characterized by a wide spectrum of auto-antibodies which recognize several cellular components. The production of these self-reactive antibodies fluctuates during the course of the disease and the involvement of different antibody-secreting cell populations are considered highly relevant for the disease pathogenesis. These cells are developed and stimulated through different ways leading to the secretion of a variety of isotypes, affinities and idiotypes. Each of them has a particular mechanism of action binding to a specific antigen and recognized by distinct receptors. The effector responses triggered lead to a chronic tissue inflammation. DsDNA autoantibodies are the most studied as well as the first in being characterized for its pathogenic role in Lupus nephritis. However, others are of growing interest since they have been associated with other organ-specific damage, such as anti-NMDAR antibodies in neuropsychiatric clinical manifestations or anti-β2GP1 antibodies in vascular symptomatology. In this review, we describe the different auto-antibodies reported to be involved in SLE. How autoantibody isotypes and affinity-binding to their antigen might result in different pathogenic responses is also discussed.

The role of neutrophils in the pathogenesis of systemic lupus erythematosus

“…Auto-antibodies in lupus include IgM, IgA, an IgG isotypes 5 , and several autoantibodies with high prevalence, disease specificity, and diagnostic utility in SLE include anti-ssDNA, anti-dsDNA, anti-cardiolipin, anti-C1q, as well as anti-nuclear antibodies (ANA) that often target nuclear components such as ribonucleoprotein, SSA/Ro, SSB/La, Smith, and histone 4 . The elevated production of autoantibodies in SLE can lead to ongoing tissue damage, providing antigenic fuel to the adaptive immune system.…”

“…Fc fragment specific, Jackson ImmunoResearch Laboratories) to detect total IgGsecreting cells. Cell suspensions from spleen, bone marrow and kidney were added to individual wells, starting with 5x105 cells in the top row and preforming a 2-fold serial dilution. Cells were incubated overnight at 37°C and 5% CO2.…”

Basophils contribute to pristane-induced Lupus-like nephritis model

“…Systemic Lupus Erythematosus (SLE) is a complex and heterogeneous autoimmune disease characterized by the production of antibodies against self-antigens mostly of nuclear origin such as double-stranded DNA and ribonucleoproteins (RNP). These autoantibodies form pathogenic immune-complexes (ICs) once aggregated to their autoantigens and complement factors 1 . Defects in B/T cell tolerance promote the uncontrolled accumulation of such ICs that interact with cells bearing Fc receptors leading to chronic inflammation and organ damage 2 , 3 .…”

Drug-induced lupus erythematosus secondary to pirfenidone

“…TNF‐α inhibitors may interfere with normal cell apoptosis, leading to a reduction in clearance of autoreactive T and B cells . Accumulation of these nucleosomes in a genetically predisposed individual may lead to the development of autoantibodies . Our patient had a predisposition for autoimmunity with a past history of psoriasis.…”