Surface‐bound anti–type II collagen–containing immune complexes induce production of tumor necrosis factor α, interleukin‐1β, and interleukin‐8 from peripheral blood monocytes via fcγ receptor IIA: A potential pathophysiologic mechanism for humoral anti–type II collagen immunity in arthritis

Mullazehi, Mohammed; Mathsson, Linda; Lampa, Jon; Rönnelid, Johan

doi:10.1002/art.21892

Cited by 70 publications

(83 citation statements)

References 45 publications

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“…C5a is a potent neutrophil chemoattractant, and mice that lack C5a receptor do not develop CAIA [143]. These processes are similar to those seen in other animal models of immune complex mediated arthritis, and are consistent with changes seen in a subset of patients with human RA who have high levels of antibodies to CII [144][145][146]. It is likely that immune complexes containing RF or ACPA exert pathogenic effects within the joint by similar mechanisms.…”

Section: Autoantibodies To Collagensupporting

confidence: 65%

The Role of Pathogenic Autoantibodies in Autoimmunity

Rowley

Whittingham

2015

Antibodies

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Abstract:The serological presence of autoantibodies is diagnostic of autoimmunity, and these autoantibodies may be present for many years before the presentation of autoimmune disease (AID). Although a pathogenic role has been demonstrated for various autoantibodies reactive with cell surface and extracellular autoantigens, studies using monoclonal antibodies (mAb) show not all antibodies in the polyclonal response are pathogenic. Differences depend on Fab-mediated diversity in epitope specificity, Fc-mediated effects based on immunoglobulin (Ig) class and subclass, activation of complement, and the milieu in which the reaction occurs. These autoantibodies often occur in organ-specific AID and this review illustrates their pathogenic and highly specific effects. The role of autoantibodies associated with intracellular antigens is less clear. In vitro they may inhibit or adversely affect well-defined intracellular biochemical pathways, yet, in vivo they are separated from their autoantigens by multiple cellular barriers. Recent evidence that Ig can traverse cell membranes, interact with intracellular proteins, and induce apoptosis has provided new evidence for a pathogenic role for such autoantibodies. An understanding of how autoantibodies behave in the polyclonal response and their role in pathogenesis of AID may help identify populations of culprit B-cells and selection of treatments that suppress or eliminate them.

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Section: Autoantibodies To Collagensupporting

confidence: 65%

The Role of Pathogenic Autoantibodies in Autoimmunity

Rowley

Whittingham

2015

Antibodies

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“…Collagen I is one of the major components of periodontal tissues (31) and, it was shown, mainly for RA, that Abs binding to self-Ags can initiate an inflammatory reaction in tissues, possibly through the release of tissue-degrading enzymes (32) and cytokines (33) by the infiltrating cells (34). In this study, the production of proinflammatory cytokines, such as TNF-a and IL-17, was enhanced by cells of AIA mice when stimulated by collagen I.…”

Section: Discussionmentioning

confidence: 54%

Experimental Arthritis Triggers Periodontal Disease in Mice: Involvement of TNF-α and the Oral Microbiota

Queiroz-Junior

Madeira

Coelho

et al. 2011

The Journal of Immunology

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Rheumatoid arthritis (RA) and periodontal disease (PD) are prevalent chronic inflammatory disorders that affect bone structures. Individuals with RA are more likely to experience PD, but how disease in joints could induce PD remains unknown. This study aimed to experimentally mimic clinical parameters of RA-induced PD and to provide mechanistic findings to explain this association. Chronic Ag-induced arthritis (AIA) was triggered by injection of methylated BSA in the knee joint of immunized mice. Anti–TNF-α was used to assess the role of this cytokine. Intra-articular challenge induced infiltration of cells, synovial hyperplasia, bone resorption, proteoglycan loss, and increased expression of cytokines exclusively in challenged joints. Simultaneously, AIA resulted in severe alveolar bone loss, migration of osteoclasts, and release of proinflammatory cytokines in maxillae. Anti–TNF-α therapy prevented the development of both AIA and PD. AIA did not modify bacterial counts in the oral cavity. PD, but not AIA, induced by injection of Ag in immunized mice was decreased by local treatment with antiseptic, which decreased the oral microbiota. AIA was associated with an increase in serum C-reactive protein levels and the expression of the transcription factors RORγ and Foxp3 in cervical lymph nodes. There were higher titers of anti-collagen I IgG, and splenocytes were more responsive to collagen I in AIA mice. In conclusion, AIA-induced PD was dependent on TNF-α and the oral microbiota. Moreover, PD was associated with changes in expression of lymphocyte transcription factors, presence of anti-collagen Abs, and increased reactivity to autoantigens.

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“…Since the Fc␥RIIa receptor is primate specific and not appearing in rodents (48), our findings argue that investigations of the effects of IC in Leishmania infection should be performed in human experimental systems. We believe that the stimulatory effect of the Fc␥RIII blockade is independent of IC because it is seen also in PEG precipitates from control individuals in this investigation, in healthy control IC (27), as well as with cultures with monomeric IgG (24). On the contrary, we have not ruled out a significant effect of Fc␥RIII since our PBMC cultures contain monocytes with very low Fc␥RIII expression (for discussion, see Ref.…”

Section: Discussionmentioning

confidence: 78%

Circulating Immune Complexes (IC) and IC-Induced Levels of GM-CSF Are Increased in Sudanese Patients with Acute Visceral Leishmania donovani Infection Undergoing Sodium Stibogluconate Treatment: Implications for Disease Pathogenesis

Elshafie

Åhlin

Mathsson

et al. 2007

The Journal of Immunology

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Infection with Leishmania donovani is associated with IL-10 as well as with GM-CSF. Immune complexes (IC) exert important functions by stimulation of monocytes/macrophage-mediated production of pro- and anti-inflammatory cytokines in rheumatic diseases. In this investigation, we have explored IC-induced cytokine production during Leishmania infection. Sera from 43 patients with visceral leishmaniasis (VL), 17 patients with post-kala-azar dermal leishmaniasis, and 20 healthy Sudanese controls were precipitated with polyethylene glycol (PEG). The PEG precipitates were added to serum-free PBMC for 20 h,whereupon supernatant levels of IL-1β, IL-6, IL-10, IL-1 receptor antagonist protein, TNF-α, TNF receptor p75, and GM-CSF were investigated using ELISA. Circulating levels of C1q-binding IC were also measured in the serum samples. PEG precipitates from Leishmania-infected patients induced significantly higher levels of GM-CSF (p = 0.0037) and IL-10 (p < 0.0001), as well as of IL-6 (p < 0.0001) and IL-1 receptor antagonist (p = 0.0238) as compared with PEG precipitates from controls. Patients with acute VL as well as VL patients receiving sodium stibogluconate treatment displayed significantly increased levels of PEG precipitate-induced GM-CSF. The induction of GM-CSF by circulating IC was especially prominent in acute VL patients receiving sodium stibogluconate treatment; ANOVA revealed significant interaction between disease activity and treatment for PEG precipitate-induced levels of GM-CSF (disease activity, p = 0.0006; treatment, p = 0.0005; interaction, p = 0.0046). Parallel associations were determined for C1q-binding immune complexes, but not for any cytokine other than GM-CSF. The importance of IC-induced GM-CSF in leishmaniasis warrants further study.

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Cited by 70 publications

References 45 publications

The Role of Pathogenic Autoantibodies in Autoimmunity

The Role of Pathogenic Autoantibodies in Autoimmunity

Experimental Arthritis Triggers Periodontal Disease in Mice: Involvement of TNF-α and the Oral Microbiota

Circulating Immune Complexes (IC) and IC-Induced Levels of GM-CSF Are Increased in Sudanese Patients with Acute Visceral Leishmania donovani Infection Undergoing Sodium Stibogluconate Treatment: Implications for Disease Pathogenesis

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