Levels of Anti-Citrullinated Protein Antibodies and Rheumatoid Factor, Including IgA Isotypes, and Articular Manifestations in Ulcerative Colitis and Crohn’s Disease

Janssen, Koen M. J.; Hop, Hilde; Vissink, Arjan; Dijkstra, Gerard; Smit, Menke J. de; Brouwer, Elisabeth; Westra, Johanna

doi:10.3390/ijerph17218054

Cited by 10 publications

(9 citation statements)

References 50 publications

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“…Inflammatory bowel diseases (IBDs) are chronic inflammatory conditions characterized by inflammation of the intestinal mucosa. The two main subtypes of IBD include ulcerative colitis (UC) and Crohn’s disease (CD) [ 136 ]. In UC patients, chronic inflammation is limited to the intestinal mucosae and in CD patients the inflammation can be transmural in the whole gastrointestinal tract [ 136 ], rendering CD more aggressive.…”

Section: Protein Citrullination As a Hallmark Of Immune Disordersmentioning

confidence: 99%

“…The two main subtypes of IBD include ulcerative colitis (UC) and Crohn’s disease (CD) [ 136 ]. In UC patients, chronic inflammation is limited to the intestinal mucosae and in CD patients the inflammation can be transmural in the whole gastrointestinal tract [ 136 ], rendering CD more aggressive. In healthy human colon enzymatic PAD activity is negligible, suggesting that deimination processes are not physiologically required in the intestine.…”

Section: Protein Citrullination As a Hallmark Of Immune Disordersmentioning

confidence: 99%

“…In contrast, PADs and citrullinated protein levels are increased in human UC [ 79 ]. As in the case of RA, elevated levels of citrullinated proteins may trigger an atypical immune response to the newly formed epitopes and high levels of ACPAs induce inflammation of the UC [ 136 , 137 ]. Moreover, immunohistochemical staining of human UC samples demonstrated strong expression of both PAD2 and PAD4, and treatment of UC mice with Cl-amidine reduced inflammation [ 137 ].…”

Section: Protein Citrullination As a Hallmark Of Immune Disordersmentioning

confidence: 99%

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Citrullination in the pathology of inflammatory and autoimmune disorders: recent advances and future perspectives

Ciesielski

Biesiekierska

Panthu

et al. 2022

Cell. Mol. Life Sci.

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Numerous post-translational modifications (PTMs) govern the collective metabolism of a cell through altering the structure and functions of proteins. The action of the most prevalent PTMs, encompassing phosphorylation, methylation, acylations, ubiquitination and glycosylation is well documented. A less explored protein PTM, conversion of peptidylarginine to citrulline, is the subject of this review. The process of citrullination is catalysed by peptidylarginine deiminases (PADs), a family of conserved enzymes expressed in a variety of human tissues. Accumulating evidence suggest that citrullination plays a significant role in regulating cellular metabolism and gene expression by affecting a multitude of pathways and modulating the chromatin status. Here, we will discuss the biochemical nature of arginine citrullination, the enzymatic machinery behind it and also provide information on the pathological consequences of citrullination in the development of inflammatory diseases (rheumatoid arthritis, multiple sclerosis, psoriasis, systemic lupus erythematosus, periodontitis and COVID-19), cancer and thromboembolism. Finally, developments on inhibitors against protein citrullination and recent clinical trials providing a promising therapeutic approach to inflammatory disease by targeting citrullination are discussed.

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Section: Protein Citrullination As a Hallmark Of Immune Disordersmentioning

confidence: 99%

Section: Protein Citrullination As a Hallmark Of Immune Disordersmentioning

confidence: 99%

Section: Protein Citrullination As a Hallmark Of Immune Disordersmentioning

confidence: 99%

See 1 more Smart Citation

Citrullination in the pathology of inflammatory and autoimmune disorders: recent advances and future perspectives

Ciesielski

Biesiekierska

Panthu

et al. 2022

Cell. Mol. Life Sci.

View full text Add to dashboard Cite

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“…Currently, studies of levels of IgA ACPA in the feces of patients with RA and at-risk individuals are missing. In patients with inflammatory bowel disease, ACPA have been demonstrated in the circulation (mostly of IgA ACPA isotype, but also IgG ACPA albeit below the diagnostic cutoff) and this has been taken as a possible sign that mucosal inflammation of the intestine can induce low systemic levels of ACPA (129).…”

Section: The Gastrointestinal Systemmentioning

confidence: 99%

Secretory Autoantibodies in Rheumatoid Arthritis

Roos

2022

Linköping University Medical Dissertations

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Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease in which autoantibodies, such as anti-citrullinated protein antibodies (ACPA), can be detected in the serum of patients. Autoantibodies may appear in the circulation years before clinical signs of joint inflammation occur, indicating that early immunological pathogenetic steps take place outside of the joints. Although many of these mechanisms are currently unknown, the initial events leading up to ACPA production are thought to occur at mucosal surfaces. In this thesis, mucosa-associated secretory ACPA are investigated in the circulation and in local mucosal secretions to: (i) improve the understanding of the mucosal connection in RA; and (ii) investigate whether these antibodies can improve diagnostics and prognostics in early RA.We identified circulating secretory component containing (SC) ACPA in a subpopulation of patients (both early and established RA) and atrisk patients, with a prevalence of 16%-21%. In addition, SC ACPA was detected in bronchoalveolar lavage fluid (BALF) and IgA ACPA in saliva, indicating local production in the lungs and in the oral cavity. In at-risk patients who were positive for IgG ACPA, we found that the levels of circulating SC ACPA at inclusion predicted arthritis development. Circulating SC ACPA was associated with higher disease activity, including increased levels of inflammatory markers, in patients with early RA. Levels of circulating SC ACPA were associated with high-resolution computed tomography (HRCT) findings (parenchymal lung abnormalities and bronchiectasis) and smoking, but not with risk genes (shared epitope). We confirmed the presence of salivary ACPA and identified a novel association with increased disease activity and functional disability.In summary, SC ACPA is present in the sera of patients with RA who manifest different phases of the disease, and we found associations with arthritis onset, smoking, systemic inflammation, and lung abnormalities. SC ACPA is also detectable in mucosal secretions from the lungs and the oral cavity. These findings suggest that mucosal ACPA production may be an important factor in RA development and progression, and that serum SC ACPA should be further evaluated as a prognostic marker for disease onset among at-risk individuals.

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“…It encompasses immunoglobulins of IgM, IgG, and IgA classes targeting the Fc-fragment of IgG. However, RF can be present in a variety of other rheumatologic and non-rheumatologic conditions, including a broad spectrum of infectious diseases -most importantly hepatitis C-virus infection and cryoglobulinemia [48], as well as cancer [49][50][51][52]. The specificity of RF in RA is estimated to be 85% at best, and the sensitivity to be in the range between 60 and 90% [52].…”

Section: Rfmentioning

confidence: 99%

Autoantibodies in Rheumatoid Arthritis: Historical Background and Novel Findings

Sokolova

Schett

Steffen

2021

Clinic Rev Allerg Immunol

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Autoantibodies represent a hallmark of rheumatoid arthritis (RA), with the rheumatoid factor (RF) and antibodies against citrullinated proteins (ACPA) being the most acknowledged ones. RA patients who are positive for RF and/or ACPA (“seropositive”) in general display a different etiology and disease course compared to so-called “seronegative” patients. Still, the seronegative patient population is very heterogeneous and not well characterized. Due to the identification of new autoantibodies and advancements in the diagnosis of rheumatic diseases in the last years, the group of seronegative patients is constantly shrinking. Aside from antibodies towards various post-translational modifications, recent studies describe autoantibodies targeting some native proteins, further broadening the spectrum of recognized antigens. Next to the detection of new autoantibody groups, much research has been done to answer the question if and how autoantibodies contribute to the pathogenesis of RA. Since autoantibodies can be detected years prior to RA onset, it is a matter of debate whether their presence alone is sufficient to trigger the disease. Nevertheless, there is gathering evidence of direct autoantibody effector functions, such as stimulation of osteoclastogenesis and synovial fibroblast migration in in vitro experiments. In addition, autoantibody positive patients display a worse clinical course and stronger radiographic progression. In this review, we discuss current findings regarding different autoantibody types, the underlying disease-driving mechanisms, the role of Fab and Fc glycosylation and clinical implications.

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Levels of Anti-Citrullinated Protein Antibodies and Rheumatoid Factor, Including IgA Isotypes, and Articular Manifestations in Ulcerative Colitis and Crohn’s Disease

Cited by 10 publications

References 50 publications

Citrullination in the pathology of inflammatory and autoimmune disorders: recent advances and future perspectives

Citrullination in the pathology of inflammatory and autoimmune disorders: recent advances and future perspectives

Secretory Autoantibodies in Rheumatoid Arthritis

Autoantibodies in Rheumatoid Arthritis: Historical Background and Novel Findings

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