Immunoglobulin (Ig)G1 and IgG4 anti-cyclic citrullinated peptide (CCP) associate with shared epitope, whereas IgG2 anti-CCP associates with smoking in patients with recent-onset rheumatoid arthritis (the Swedish TIRA project)

Martinsson, Κjell; Johansson, Anders; Kastbom, Alf

doi:10.1111/cei.12901

Cited by 10 publications

(20 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, in one study of patients with RA, smoking was not associated with anti-CCP, citrullinated vimentin or citrullinated fibrinogen antibodies, but was associated with citrullinated alpha-enolase peptide antibodies [ 29 ]. Another recent study demonstrated that only IgG2 and IgA isotypes of anti-CCP antibodies associated with smoking, while IgG1 and IgG4 anti-CCP antibodies were associated with having SE [ 30 ]. These findings suggest that the relationship between smoking, citrullination, and the autoantibody response in RA is more nuanced than previously appreciated.…”

Section: Discussionmentioning

confidence: 99%

Smoking is not linked to the development of anti-peptidylarginine deiminase 4 autoantibodies in rheumatoid arthritis

et al. 2018

View full text Add to dashboard Cite

BackgroundDefining environmental factors responsible for development of autoimmunity in rheumatoid arthritis (RA) is critical for understanding mechanisms of disease initiation and propagation. Notably, a history of cigarette smoking has been implicated in the genesis of RA and is associated with worse disease outcomes. Antibodies to peptidylarginine deiminase 4 (PAD4) are also associated with more severe RA. A subset of patients who have PAD4 autoantibodies that cross-react with PAD3 (anti-PAD3/4) are at the highest risk for interstitial lung disease, and this risk is augmented by a history of cigarette smoking. It is unclear, however, if smoking is etiologically linked to the development of anti-PAD4 antibodies.MethodsPatients were included in this study if they had physician-diagnosed RA as well as DNA, serum, and a date-matched clinical assessment (n = 274). Anti-PAD4 and anti-CCP antibodies were measured by immunoprecipitation and ELISA, respectively; shared epitope (SE) status was determined by HLA-DRβ1 genotyping. Logistic regression analysis was used to evaluate associations of smoking with PAD4 antibodies, with adjustment for relevant demographic and clinical features. Stratified analyses by disease duration and shared epitope status were also performed.ResultsAnti-PAD4 antibodies were present in 25% of RA patients, with 50% of these individuals having anti-PAD3/4 cross-reactive antibodies. Anti-PAD4 antibodies were significantly associated with a longer disease duration, SE alleles, and anti-CCP antibodies. Importantly, there were no significant differences in smoking history between anti-PAD4 positive and negative groups in univariate analyses, stratified analyses, or multivariable models. However, an inverse relationship between smoking and anti-PAD4 antibodies was suggested by a lower prevalence of current smokers among patients with anti-PAD3/4 antibodies compared to antibody negative individuals (p = 0.04). Further, the lowest levels of anti-PAD4 antibodies were observed in current smokers (p = 0.14), and a significant association of SE and anti-PAD4 antibodies was only present among never smokers (p = 0.01).ConclusionsSmoking history was not associated with anti-PAD4 antibodies in patients with RA. The finding that anti-PAD4 antibodies were not associated with smoking suggests that other environmental factors may contribute to the development of autoimmunity to PAD4 in these patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Smoking is not linked to the development of anti-peptidylarginine deiminase 4 autoantibodies in rheumatoid arthritis

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Immunologically, anti-CCP antibodies are autoantibodies that are directed against cyclic citrullinated peptides [19][20][21]. In the present case, serum anti-CCP Ab was strongly positive at the time of RB; therefore, we suspected the involvement of anti-CCP Ab in the development of MN directly due to RA.…”

Section: Discussionmentioning

confidence: 50%

Membranous nephropathy caused by rheumatoid arthritis

et al. 2019

View full text Add to dashboard Cite

Membranous nephropathy (MN) caused by disease-modifying antirheumatic drugs is relatively common in patients with rheumatoid arthritis (RA). However, MN rarely occurs due to RA itself. We describe a 61-year-old woman with RA who showed nephrotic syndrome. She was admitted because of systemic edema and severe arthritis. She had a long history of RA successfully treated with methotrexate (MTX), but discontinued all treatments 4 years before hospitalization. She had never been treated with bucillamine or gold. Laboratory test results were positive for anti-cyclic citrullinated peptide antibody and negative for anti-nuclear antibody. Renal pathologic findings were compatible with MN. Immunofluorescence microscopy showed IgG, IgA, κ, λ, and C3 along the glomerular capillary wall, whereas deposition of IgM or C1q was not detected. In terms of the IgG subclasses, only IgG2 findings were positive. Results for glomerular antigen and serum antibody for M-type phospholipase A2 receptor and thrombospondin type 1 domain-containing 7A were negative. HLA type did not include the HLA-DQA1 gene that is a concern in primary MN (PMN). She responded to intensive immunosuppressive therapy consisting of prednisolone, tacrolimus, and MTX with a parallel reduction of proteinuria. Based on assessments for differentiating PMN from secondary MN (SMN), the diagnosis of the present case was incompatible with PMN. Taken together, we consider that SMN in the present case was due to RA itself rather than drug-induced MN.

show abstract

“…The relatively strong HLA association of a 'shared epitope' was more distinctly related to the IgG4 and IgG1 isotypes of the cyclic citrullinated peptide (CCP) autoantibodies in RA [19,20]. The relatively strong HLA association of a 'shared epitope' was more distinctly related to the IgG4 and IgG1 isotypes of the cyclic citrullinated peptide (CCP) autoantibodies in RA [19,20].…”

Section: Discussionmentioning

confidence: 99%

“…HLA associations have been implicated in the regulation of autoantibody production in other autoimmune diseases. The relatively strong HLA association of a 'shared epitope' was more distinctly related to the IgG4 and IgG1 isotypes of the cyclic citrullinated peptide (CCP) autoantibodies in RA [19,20]. The higher levels of autoantibodies were also associated with certain HLA alleles, implying that the differential expression of these alleles is a mechanism that contributes to the susceptibility and/or disease progression of RA [28].…”

Section: Discussionmentioning

confidence: 99%

“…HLA associations are detected with many autoimmune diseases, as in MG. Efforts to explain the role of HLA in disease pathogenesis have been focused on the antigenpresenting functions of these molecules to T cells [18]. The regulation of autoantibody production has also been shown to be related to HLA associations in rheumatoid arthritis (RA) [19,20]. The stratification of patients according to the presence of cyclic citrullinated peptide (CCP) autoantibodies has also revealed genetically distinct subgroups [21].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Relation ofHLA-DRB1to IgG4 autoantibody and cytokine production in muscle-specific tyrosine kinase myasthenia gravis (MuSK-MG)

Çebi

Durmuş

Yılmaz

et al. 2019

Clinical and Experimental Immunology

View full text Add to dashboard Cite

A small subset of myasthenia gravis (MG) patients develop autoantibodies against muscle-specific kinase (MuSK), which are predominantly of the immunoglobulin (Ig)G4 isotype. MuSK-MG is strongly associated with HLA-DRB1*14, HLA-DRB1*16 and HLA-DQB1*05. In this study, the possible effects of these HLA associations on MuSK IgG autoantibody or cytokine production were investigated. Samples from 80 MG patients with MuSK antibodies were studied. The disease-associated HLA types were screened in the DNA samples. The IgG1, IgG2, IgG3 and IgG4 titres of the MuSK antibodies and the levels of interleukin (IL)-4, IL-6, IL-17A and IL-10 were measured in the sera. Comparisons were made among the groups with or without HLA-DRB1*14, HLA-DRB1*16 or HLA-DQB1*05. The IgG4 titres of the MuSK antibodies were higher than those of the IgG1, IgG2 and IgG3 isotypes among the whole group of patients. DRB1*14 (+) DRB1*16 (-) patients had higher levels of IgG4 antibodies than those of DRB1*14 (-) DRB1*16 (+) patients. DRB1*14 (+) DRB1*16 (+) patients also had higher levels of IgG4 antibodies than those of DRB1*14 (-) DRB1*16 (+) and DRB1*14 (-) DRB1*16 (-) patients. Higher IL-10 and lower IL-17A levels were measured in DRB1*14 (+) DRB1*16 (-) patients than in DRB1*14 (-) DRB1*16 (-) patients. The higher IgG4 titres of MuSK autoantibodies in patients carrying HLA-DRB1*14 than those in the other patients suggest a role for HLA in the production of the antibodies. The differences in IL-10 and IL-17A support the role of DRB1 in the etiopathogenesis of this autoimmune response.

show abstract

Immunoglobulin (Ig)G1 and IgG4 anti-cyclic citrullinated peptide (CCP) associate with shared epitope, whereas IgG2 anti-CCP associates with smoking in patients with recent-onset rheumatoid arthritis (the Swedish TIRA project)

Cited by 10 publications

References 47 publications

Smoking is not linked to the development of anti-peptidylarginine deiminase 4 autoantibodies in rheumatoid arthritis

Smoking is not linked to the development of anti-peptidylarginine deiminase 4 autoantibodies in rheumatoid arthritis

Membranous nephropathy caused by rheumatoid arthritis

Relation ofHLA-DRB1to IgG4 autoantibody and cytokine production in muscle-specific tyrosine kinase myasthenia gravis (MuSK-MG)

Contact Info

Product

Resources

About