Salivary IgA antibodies to cyclic citrullinated peptides (CCP) in rheumatoid arthritis

Svärd, Anna; Kastbom, Alf; Sommarin, Yngve; Skogh, Thomas

doi:10.1016/j.imbio.2012.04.011

Cited by 29 publications

(32 citation statements)

References 49 publications

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“…In humans, circulating IgA is mainly monomeric, while SIgA is a dimeric or polymeric molecule linked together by a joining chain (J-chain) and complexed with secretory component (SC) [14]. We have shown recently that ACPA SIgA can be detected not only in mucosal fluids [15], but also in sera from recent-onset RA patients [15,16].…”

Section: Introductionmentioning

confidence: 99%

Changes in anti-citrullinated protein antibody isotype levels in relation to disease activity and response to treatment in early rheumatoid arthritis

Kastbom

Ljungberg

Ziegelasch

et al. 2018

Clinical and Experimental Immunology

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Rheumatoid arthritis (RA) is a chronic inflammatory disease where serum analysis of anti-citrullinated peptide/protein antibodies (ACPA) is an important diagnostic/prognostic tool. Levels and changes of ACPA in RA patients have been studied previously in relation to disease course and therapy response, but less is known regarding ACPA isotype changes in early RA. Hence, recent-onset RA patients (n = 231) were subjected to a 3-year clinical and radiological follow-up. Serum samples were serially collected and ACPA isotypes were analysed using the second-generation cyclic citrullinated peptide (CCP) as capture antigen. Changes in ACPA isotype levels and status were related to disease course and pharmacotherapy. At inclusion, 74% of the patients tested positive for ACPA IgG; 55% for immunoglobulin (Ig)A, 37% for secretory IgA (SIgA) and 35% for IgM. The proportion of positive patients decreased significantly at follow-up regarding ACPA SIgA, IgM and IgA. During the initial 3 months, reduction of the 28-joint disease activity score (DAS28) correlated with reduced levels of ACPA IgG (Rho = 0·242, P = 0·003), IgA (Rho = 0·260, P = 0·008), IgM (Rho = 0·457, P < 0·001) and SIgA (Rho = 0·402, P < 0·001). Levels of ACPA SIgA (P = 0·008) and IgM (P = 0·021) decreased significantly among patients with good response to treatment, which was not seen regarding ACPA IgA or IgG. Changes in ACPA isotype levels were not associated with radiographic damage. In conclusion, ACPA SIgA and IgM declined rapidly upon anti-rheumatic therapy and correlated with decreased disease activity in recent-onset RA. This may indicate that down-regulation of mucosal immunity to citrullinated proteins/peptides and recruitment of new B cells are key features of therapy responses in early RA.

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Section: Introductionmentioning

confidence: 99%

Changes in anti-citrullinated protein antibody isotype levels in relation to disease activity and response to treatment in early rheumatoid arthritis

Kastbom

Ljungberg

Ziegelasch

et al. 2018

Clinical and Experimental Immunology

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“…Downmodulation of AIA may involve modulation of the anti-mBSA antibody repertoire from IgG2a and 2b toward IgG1 and IgA, which are less inflammatory [16]. Likewise, induction of mucosal IgA against CCP is associated with less-severe RA [17]. Also, in Lyme-induced arthritis, treatment with subtoxic doses of inorganic mercury clearly ameliorates arthritis, while increasing circulating levels of total IgE [18].…”

Section: Introductionmentioning

confidence: 99%

Interferon alpha inhibits antigen-specific production of proinflammatory cytokines and enhances antigen-specific transforming growth factor beta production in antigen-induced arthritis

et al. 2013

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IntroductionInterferon alpha (IFN-α) has a complex role in autoimmunity, in that it may both enhance and prevent inflammation. We have previously shown that the presence of IFN-α at sensitization protects against subsequent antigen-triggered arthritis. To understand this tolerogenic mechanism, we performed a descriptive, hypothesis-generating study of cellular and humoral responses associated with IFN-α-mediated protection against arthritis.MethodsArthritis was evaluated at day 28 in mice given a subcutaneous injection of methylated bovine serum albumin (mBSA), together with Freund adjuvant and 0 to 5,000 U IFN-α at days 1 and 7, followed by intraarticular injection of mBSA alone at day 21. The effect of IFN-α on mBSA-specific IgG1, IgG2a, IgG2b, IgA, and IgE was evaluated by enzyme-linked immunosorbent assay (ELISA). Cytokines in circulation and in ex vivo cultures on mBSA restimulation was evaluated with ELISA and Luminex, and the identity of cytokine-producing cells by fluorescence-activated cell sorting (FACS) analysis.ResultsAdministration of IFN-α protected mice from arthritis in a dose-dependent manner but had no effect on antigen-specific antibody levels. However, IFN-α did inhibit the initial increase of IL-6, IL-10, IL-12, and TNF, and the recall response induced by intraarticular mBSA challenge of IL-1β, IL-10, IL-12, TNF, IFN-γ, and IL-17 in serum. IFN-α decreased both macrophage and CD4+ T cell-derived IFN-γ production, whereas IL-17 was decreased only in CD4+ T cells. Ex vivo, in mBSA-restimulated spleen and lymph node cell cultures, the inhibitory effect of in vivo administration of IFN-α on proinflammatory cytokine production was clearly apparent, but had a time limit. An earlier macrophage-derived, and stronger activation of the antiinflammatory cytokine transforming growth factor beta (TGF-β) was observed in IFN-α-treated animals, combined with an increase in CD4+ T cells producing TGF-β when arthritis was triggered by mBSA (day 21). Presence of IFN-α at immunizations also prevented the reduction in TGF-β production, which was induced by the intraarticular mBSA injection triggering arthritis in control animals.ConclusionsAdministration of IFN-α has a profound effect on the cellular response to mBSA plus adjuvant, but does not affect antigen-specific Ig production. By including IFN-α at immunizations, spleen and lymph node cells inhibit their repertoire of antigen-induced proinflammatory cytokines while enhancing antiinflammatory TGF-β production, first in macrophages, and later also in CD4+ T cells. On intraarticular antigen challenge, this antiinflammatory state is reenforced, manifested as inhibition of proinflammatory recall responses and preservation of TGF-β levels. This may explain why IFN-α protects against antigen-induced arthritis.

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“…A particularly interesting example of effects of different glycosylation patterns have been provided from studies, on antibodies that have been modified by enzymes from bacteria, in which these enzymes appear to have evolved during evolution to modify IgG antibodies so that they do not bind complement or Fc receptors [49]. In addition, IgA ACPAs have been described and suggested to mediate protective effects [52]. A very recent study [50 && ] indicates, that such deglycosylated IgG molecules may indeed inhibit immune complex dependent inflammation even when the deglycosylated antibodies are not directed to the targets of the pathogenic antibodies.…”

Section: Resultsmentioning

confidence: 99%

Adaptive immunity in rheumatoid arthritis

Klareskog

Amara

Malmström

2014

Current Opinion in Rheumatology

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Several different triggering mechanisms are involved in forming an antibody repertoire that evolves before the onset of clinical disease, and where antibodies with different specificities may interact directly or indirectly with target organs in causing different arthritis-associated symptoms. The increasing understanding of the role of adaptive and specific immunity in RA creates opportunities for a new generation of interventions.

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Salivary IgA antibodies to cyclic citrullinated peptides (CCP) in rheumatoid arthritis

Cited by 29 publications

References 49 publications

Changes in anti-citrullinated protein antibody isotype levels in relation to disease activity and response to treatment in early rheumatoid arthritis

Changes in anti-citrullinated protein antibody isotype levels in relation to disease activity and response to treatment in early rheumatoid arthritis

Interferon alpha inhibits antigen-specific production of proinflammatory cytokines and enhances antigen-specific transforming growth factor beta production in antigen-induced arthritis

Adaptive immunity in rheumatoid arthritis

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