Work

Commentary: Antibodies against multiple post-translationally modified proteins aid in diagnosis of autoimmune hepatitis and associate with complete biochemical response to treatment

Year: 2023

Type: editorial

Abstract: Commentary on: van den Beukel MD, Stoelinga AEC, van der Meer AJ, van der Meulen S, Zhang L, Tushuizen ME, van Hoek B and Trouw LA (2023). Antibodies against multiple posttranslationally modified proteins aid in diagnosis of autoimmune hepatitis and associate with complete biochemical response to treatment. Front. Med. 10:1195747. doi: 10.3389/fmed.2023.1195747We read with great interest the article "Antibodies against multiple post-translationally modified proteins aid in diagnosis of autoimmune hepatitis and associate with complete biochemical response to treatment" by van den Beukel and Stoelinga et al (1). First of all, we would like to congratulate the authors on their interesting finding that immunoglobulin G (IgG) against posttranslationally modified (PTM) proteins are also found in autoimmune liver diseases and especially in untreated autoimmune hepatitis (AIH) and not only in rheumatologic autoimmune diseases. In particular, the association of antibody patterns of positivity for multiple anti-PTM antibodies with treatment response has the potential to impact the care of patients with AIH.Recently, we have identified a polyreactivity of IgG (pIgG) especially in patients with untreated AIH. That is, IgG from patients with untreated AIH were significantly more reactive against multiple foreign protein and non-protein antigens, as well as against multiple autoantigens, than patients with non-AIH liver diseases or healthy controls in adults and children (2,3). We identified pIgG with a similar solid phase ELISA immunoassay using the same plastic ELISA plates (Nunc Maxisorb) with the same blocking reagent bovine serum albumin (BSA) as van den Beukel and Stoelinga et al. In addition, IgG from AIH patients showed increased binding to these BSA-blocked ELISA plates even without the addition of foreign antigens or autoantigens to the ELISA plates. Interestingly, BSA showed the strongest binding of pIgG of all blocking reagents tested. The addition of some (e.g. HIP1R) but not all autoantigens tested (e.g. ITSN1) further increased the binding of pIgG compared to BSA alone. This polyreactivity could only partially be eliminated by further dilution, preincubation of patient serum with the If polyreactivity of IgG caused the anti-PTM reactivity, a significant correlation of the different anti-PTM reactivities should be found. We and others have shown that pIgG can be associated with false positive results even in commercially available autoantibody ELISAs for autoimmune liver diseases (4,5).However, there are also differences between pIgG and anti-PTM antibodies in AIH patients.Anti-PTM antibodies or at least combinations of different anti-PTM antibodies at baseline, before initiation of therapy, were associated with the treatment response in AIH patients, while we found no such association for pIgG concentrations.Another source of bias in the detection of autoantibodies from cryopreserved serum or plasma is the increase of pIgG with storage time, as we have recently demonstrated (3). Van den Beukel and Stoelinga et al. used serum after up to 24 years of cryopreservation, a period in which we observed a relevant increase in polyreactivity of IgG. Did the authors find a correlation of reactivity in anti-PTM assays with storage time? Or did the authors normalize the reactivities in their PTM ELISAs for storage time? Polyreactivity of IgG is not limited to autoimmune liver diseases, but is often found in diseases with high inflammation and even more often in diseases with polyclonal hypergammaglobulinemia (5). PIgG appears to be generated during class switching from IgM to IgG and during somatic hypermutation in the transition to IgG+ memory B cells (6,7). Thus, pIgG and hypergammaglobulinemia may be produced when T helper cells stimulate B cells in a manner dependent and independent of B cell receptor specificity (6). The finding that AIH patients have an AIH-specific T cell receptor repertoire but not an AIH-specific B cell receptor repertoire is consistent with this pathophysiological concept (8). In addition, polyclonality of autoantibodies and IgG is also found in experimental mouse models of AIH (9,10).In conclusion, polyreactivity of IgG to multiple protein and non-protein antigens, including typical ELISA blocking reagents, is a common finding in untreated AIH. All immunoassays

Source: Frontiers in Medicine

DOI: 10.3389/fmed.2023.1275838

Authors: Richard Taubert, Bastian Engel, Alejandro Campos-Murguia

Institution: Medizinische Hochschule Hannover

Language: English

Topic: Liver Diseases and Immunity

Subfield: Hepatology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,295