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Frequency and Clinical Significance of Elevated IgG4 in Rheumatoid Arthritis: A Systematic Review

Immunoglobulin (Ig)G4 is a unique protein molecule and its role in autoimmune diseases remains elusive and controversial. Accumulating evidence suggests a pathogenic role of IgG4 in rheumatoid arthritis (RA). Rheumatoid factors (RF) in RA can recognize the Fc domains of IgG4 to form RF-IgG4 immune c...

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Autores principales: Sakthiswary, Rajalingham, Shaharir, Syahrul Sazliyana, Wahab, Asrul Abdul
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8945114/
https://www.ncbi.nlm.nih.gov/pubmed/35327360
http://dx.doi.org/10.3390/biomedicines10030558
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author Sakthiswary, Rajalingham
Shaharir, Syahrul Sazliyana
Wahab, Asrul Abdul
author_facet Sakthiswary, Rajalingham
Shaharir, Syahrul Sazliyana
Wahab, Asrul Abdul
author_sort Sakthiswary, Rajalingham
collection PubMed
description Immunoglobulin (Ig)G4 is a unique protein molecule and its role in autoimmune diseases remains elusive and controversial. Accumulating evidence suggests a pathogenic role of IgG4 in rheumatoid arthritis (RA). Rheumatoid factors (RF) in RA can recognize the Fc domains of IgG4 to form RF-IgG4 immune complexes that may activate the complement system leading to synovial injury. The aim of this article was to systematically review the literature from the past 2 decades to determine the frequency of elevated IgG4 and its clinical significance in RA. We comprehensively searched the Pubmed, Scopus, and Web of Science databases with the following terms: “IgG4”, “rheumatoid arthritis”, and “immunoglobulin G4”, and scrutinized all of the relevant publications. Based on the selection criteria, 12 studies were incorporated, which involved a total of 1715 RA patients. Out of 328 subjects from three studies, the pooled frequency of elevated non-specific IgG4 was 35.98%. There was a significant positive correlation between the IgG4 levels and the RA disease activity based on DAS-28 measurements (r = 0.245–0.253) and inflammatory markers, i.e., erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels (r = 0.262–0.389). Longitudinal studies that measured the serial levels of IgG4 consistently showed a decline in the concentrations (up to 48% less than baseline) with disease modifying anti-rheumatic drug (DMARD) treatment. Current evidence suggests that serum IgG4 levels are significantly elevated in RA compared to the general population. This review indicates that IgG4 is a promising biomarker of disease activity and tends to decline in response to DMARD therapies. Biologic therapies have revolutionized the therapeutic armamentarium of RA in the recent decade, and IgG4 appears to be a potential treatment target.
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spelling pubmed-89451142022-03-25 Frequency and Clinical Significance of Elevated IgG4 in Rheumatoid Arthritis: A Systematic Review Sakthiswary, Rajalingham Shaharir, Syahrul Sazliyana Wahab, Asrul Abdul Biomedicines Systematic Review Immunoglobulin (Ig)G4 is a unique protein molecule and its role in autoimmune diseases remains elusive and controversial. Accumulating evidence suggests a pathogenic role of IgG4 in rheumatoid arthritis (RA). Rheumatoid factors (RF) in RA can recognize the Fc domains of IgG4 to form RF-IgG4 immune complexes that may activate the complement system leading to synovial injury. The aim of this article was to systematically review the literature from the past 2 decades to determine the frequency of elevated IgG4 and its clinical significance in RA. We comprehensively searched the Pubmed, Scopus, and Web of Science databases with the following terms: “IgG4”, “rheumatoid arthritis”, and “immunoglobulin G4”, and scrutinized all of the relevant publications. Based on the selection criteria, 12 studies were incorporated, which involved a total of 1715 RA patients. Out of 328 subjects from three studies, the pooled frequency of elevated non-specific IgG4 was 35.98%. There was a significant positive correlation between the IgG4 levels and the RA disease activity based on DAS-28 measurements (r = 0.245–0.253) and inflammatory markers, i.e., erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels (r = 0.262–0.389). Longitudinal studies that measured the serial levels of IgG4 consistently showed a decline in the concentrations (up to 48% less than baseline) with disease modifying anti-rheumatic drug (DMARD) treatment. Current evidence suggests that serum IgG4 levels are significantly elevated in RA compared to the general population. This review indicates that IgG4 is a promising biomarker of disease activity and tends to decline in response to DMARD therapies. Biologic therapies have revolutionized the therapeutic armamentarium of RA in the recent decade, and IgG4 appears to be a potential treatment target. MDPI 2022-02-26 /pmc/articles/PMC8945114/ /pubmed/35327360 http://dx.doi.org/10.3390/biomedicines10030558 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Systematic Review
Sakthiswary, Rajalingham
Shaharir, Syahrul Sazliyana
Wahab, Asrul Abdul
Frequency and Clinical Significance of Elevated IgG4 in Rheumatoid Arthritis: A Systematic Review
title Frequency and Clinical Significance of Elevated IgG4 in Rheumatoid Arthritis: A Systematic Review
title_full Frequency and Clinical Significance of Elevated IgG4 in Rheumatoid Arthritis: A Systematic Review
title_fullStr Frequency and Clinical Significance of Elevated IgG4 in Rheumatoid Arthritis: A Systematic Review
title_full_unstemmed Frequency and Clinical Significance of Elevated IgG4 in Rheumatoid Arthritis: A Systematic Review
title_short Frequency and Clinical Significance of Elevated IgG4 in Rheumatoid Arthritis: A Systematic Review
title_sort frequency and clinical significance of elevated igg4 in rheumatoid arthritis: a systematic review
topic Systematic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8945114/
https://www.ncbi.nlm.nih.gov/pubmed/35327360
http://dx.doi.org/10.3390/biomedicines10030558
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