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Rheumatoid arthritis-associated autoantibodies in non-rheumatoid arthritis patients with mucosal inflammation: a case-control study.

Janssen KM, de Smit MJ, Brouwer E, de Kok FA, Kraan J, Altenburg J, Verheul MK, Trouw LA, van Winkelhoff AJ, Vissink A, Westra J - Arthritis Res. Ther. (2015)

Bottom Line: Logistic regression analysis revealed that IgG anti-CCP seropositivity was associated with BR and RA, whereas the association with PD was borderline significant.IgM RF seropositivity was associated with RA, whereas the association with BR was borderline significant.IgA RF seropositivity was associated with CF and RA.

View Article: PubMed Central - PubMed

Affiliation: Department of Oral and Maxillofacial Surgery, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands. k.m.j.janssen@umcg.nl.

ABSTRACT

Introduction: Rheumatoid arthritis-associated autoantibodies (RA-AAB) can be present in serum years before clinical onset of rheumatoid arthritis (RA). It has been hypothesized that initiation of RA-AAB generation occurs at inflamed mucosal surfaces, such as in the oral cavity or lungs. The aim of this study was to assess systemic presence of RA-AAB in patients without RA who had oral or lung mucosal inflammation.

Methods: The presence of RA-AAB (immunoglobulin A [IgA] and IgG anti-cyclic citrullinated peptide 2 antibodies (anti-CCP2), IgM and IgA rheumatoid factor (RF), IgG anti-carbamylated protein antibodies and IgG and IgA anti-citrullinated peptide antibodies against fibrinogen, vimentin and enolase) were determined in sera of non-RA patients with periodontitis (PD, n = 114), bronchiectasis (BR, n = 80) or cystic fibrosis (CF, n = 41). Serum RA-AAB levels were compared with those of periodontally healthy controls (n = 36). Patients with established RA (n = 86) served as a reference group. Association of the diseases with RA-AAB seropositivity was assessed with a logistic regression model, adjusted for age, sex and smoking.

Results: Logistic regression analysis revealed that IgG anti-CCP seropositivity was associated with BR and RA, whereas the association with PD was borderline significant. IgA anti-CCP seropositivity was associated with CF and RA. IgM RF seropositivity was associated with RA, whereas the association with BR was borderline significant. IgA RF seropositivity was associated with CF and RA. Apart from an influence of smoking on IgA RF in patients with RA, there was no influence of age, sex or smoking on the association of RA-AAB seropositivity with the diseases. Anti-CarP levels were increased only in patients with RA. The same held for IgG reactivity against all investigated citrullinated peptides.

Conclusion: Although overall levels were low, RA-AAB seropositivity was associated with lung mucosal inflammation (BR and CF) and may be associated with oral mucosal inflammation (PD). To further determine whether mucosal inflammation functions as a site for induction of RA-AAB and precedes RA, longitudinal studies are necessary in which RA-AAB of specifically the IgA isotype should be assessed in inflamed mucosal tissues and/or in their inflammatory exudates.

No MeSH data available.


Related in: MedlinePlus

Serum immunoglobulin G (IgG) (a) and IgA anti-cyclic arginine peptide (anti-CAP) (b) levels in healthy controls (HC) and in patients with periodontitis (PD), bronchiectasis (BR), cystic fibrosis (CF) and rheumatoid arthritis (RA). CAP represents the native counterpart of CCP. Cutoff values are indicated: >2 SD above the mean of HC. Bar indicates the median. *p < 0.05, **p < 0.01, Kruskal–Wallis one-way analysis of variance with Dunn’s multiple-comparisons post-test compared with HC if overall p < 0.05
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Fig2: Serum immunoglobulin G (IgG) (a) and IgA anti-cyclic arginine peptide (anti-CAP) (b) levels in healthy controls (HC) and in patients with periodontitis (PD), bronchiectasis (BR), cystic fibrosis (CF) and rheumatoid arthritis (RA). CAP represents the native counterpart of CCP. Cutoff values are indicated: >2 SD above the mean of HC. Bar indicates the median. *p < 0.05, **p < 0.01, Kruskal–Wallis one-way analysis of variance with Dunn’s multiple-comparisons post-test compared with HC if overall p < 0.05

Mentions: Compared with HC, IgG and IgA anti-CCP levels were increased in patients with CF (both p < 0.01) and patients with RA (both p < 0.0001). IgG anti-CCP seropositivity was 13 %, 21 %, 24 % and 86 % in PD, BR, CF and RA patients, respectively, and 5.6 % in HC. According to the diagnostic cutoff, IgG anti-CCP seropositivity was 0.9 %, 3.8 %, 2.4 % and 76 % in PD, BR, CF and RA, respectively, and absent in HC. Seropositivity for IgA anti-CCP was 16 %, 10 %, 27 % and 74 % in PD, BR, CF and RA patients, respectively, and 8.3 % in HC (Fig. 1). Reactivity against the native counterpart of CCP (anti-CAP) was, compared with HC, increased in RA patients for IgG anti-CAP (p < 0.01) and in CF patients for IgA anti-CAP (p < 0.05), although this was not necessarily reflected in increased seropositivity (Fig. 2). Correlations for IgG anti-CCP and IgG anti-CAP levels were found in HC (ρ = 0.57, p < 0.001), patients with PD (ρ = 0.32, p < 0.001) and patients with BR (ρ = 0.47, p < 0.0001), and a trend was observed in patients with CF (ρ = 0.28, p = 0.08). IgA anti-CCP and IgA anti-CAP levels were correlated in HC (ρ = 0.41, p < 0.05), patients with PD (ρ = 0.39, p < 0.0001), patients with CF (ρ = 0.38, p < 0.05) and patients with RA (ρ = 0.21, p < 0.05).Fig. 1


Rheumatoid arthritis-associated autoantibodies in non-rheumatoid arthritis patients with mucosal inflammation: a case-control study.

Janssen KM, de Smit MJ, Brouwer E, de Kok FA, Kraan J, Altenburg J, Verheul MK, Trouw LA, van Winkelhoff AJ, Vissink A, Westra J - Arthritis Res. Ther. (2015)

Serum immunoglobulin G (IgG) (a) and IgA anti-cyclic arginine peptide (anti-CAP) (b) levels in healthy controls (HC) and in patients with periodontitis (PD), bronchiectasis (BR), cystic fibrosis (CF) and rheumatoid arthritis (RA). CAP represents the native counterpart of CCP. Cutoff values are indicated: >2 SD above the mean of HC. Bar indicates the median. *p < 0.05, **p < 0.01, Kruskal–Wallis one-way analysis of variance with Dunn’s multiple-comparisons post-test compared with HC if overall p < 0.05
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4496865&req=5

Fig2: Serum immunoglobulin G (IgG) (a) and IgA anti-cyclic arginine peptide (anti-CAP) (b) levels in healthy controls (HC) and in patients with periodontitis (PD), bronchiectasis (BR), cystic fibrosis (CF) and rheumatoid arthritis (RA). CAP represents the native counterpart of CCP. Cutoff values are indicated: >2 SD above the mean of HC. Bar indicates the median. *p < 0.05, **p < 0.01, Kruskal–Wallis one-way analysis of variance with Dunn’s multiple-comparisons post-test compared with HC if overall p < 0.05
Mentions: Compared with HC, IgG and IgA anti-CCP levels were increased in patients with CF (both p < 0.01) and patients with RA (both p < 0.0001). IgG anti-CCP seropositivity was 13 %, 21 %, 24 % and 86 % in PD, BR, CF and RA patients, respectively, and 5.6 % in HC. According to the diagnostic cutoff, IgG anti-CCP seropositivity was 0.9 %, 3.8 %, 2.4 % and 76 % in PD, BR, CF and RA, respectively, and absent in HC. Seropositivity for IgA anti-CCP was 16 %, 10 %, 27 % and 74 % in PD, BR, CF and RA patients, respectively, and 8.3 % in HC (Fig. 1). Reactivity against the native counterpart of CCP (anti-CAP) was, compared with HC, increased in RA patients for IgG anti-CAP (p < 0.01) and in CF patients for IgA anti-CAP (p < 0.05), although this was not necessarily reflected in increased seropositivity (Fig. 2). Correlations for IgG anti-CCP and IgG anti-CAP levels were found in HC (ρ = 0.57, p < 0.001), patients with PD (ρ = 0.32, p < 0.001) and patients with BR (ρ = 0.47, p < 0.0001), and a trend was observed in patients with CF (ρ = 0.28, p = 0.08). IgA anti-CCP and IgA anti-CAP levels were correlated in HC (ρ = 0.41, p < 0.05), patients with PD (ρ = 0.39, p < 0.0001), patients with CF (ρ = 0.38, p < 0.05) and patients with RA (ρ = 0.21, p < 0.05).Fig. 1

Bottom Line: Logistic regression analysis revealed that IgG anti-CCP seropositivity was associated with BR and RA, whereas the association with PD was borderline significant.IgM RF seropositivity was associated with RA, whereas the association with BR was borderline significant.IgA RF seropositivity was associated with CF and RA.

View Article: PubMed Central - PubMed

Affiliation: Department of Oral and Maxillofacial Surgery, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands. k.m.j.janssen@umcg.nl.

ABSTRACT

Introduction: Rheumatoid arthritis-associated autoantibodies (RA-AAB) can be present in serum years before clinical onset of rheumatoid arthritis (RA). It has been hypothesized that initiation of RA-AAB generation occurs at inflamed mucosal surfaces, such as in the oral cavity or lungs. The aim of this study was to assess systemic presence of RA-AAB in patients without RA who had oral or lung mucosal inflammation.

Methods: The presence of RA-AAB (immunoglobulin A [IgA] and IgG anti-cyclic citrullinated peptide 2 antibodies (anti-CCP2), IgM and IgA rheumatoid factor (RF), IgG anti-carbamylated protein antibodies and IgG and IgA anti-citrullinated peptide antibodies against fibrinogen, vimentin and enolase) were determined in sera of non-RA patients with periodontitis (PD, n = 114), bronchiectasis (BR, n = 80) or cystic fibrosis (CF, n = 41). Serum RA-AAB levels were compared with those of periodontally healthy controls (n = 36). Patients with established RA (n = 86) served as a reference group. Association of the diseases with RA-AAB seropositivity was assessed with a logistic regression model, adjusted for age, sex and smoking.

Results: Logistic regression analysis revealed that IgG anti-CCP seropositivity was associated with BR and RA, whereas the association with PD was borderline significant. IgA anti-CCP seropositivity was associated with CF and RA. IgM RF seropositivity was associated with RA, whereas the association with BR was borderline significant. IgA RF seropositivity was associated with CF and RA. Apart from an influence of smoking on IgA RF in patients with RA, there was no influence of age, sex or smoking on the association of RA-AAB seropositivity with the diseases. Anti-CarP levels were increased only in patients with RA. The same held for IgG reactivity against all investigated citrullinated peptides.

Conclusion: Although overall levels were low, RA-AAB seropositivity was associated with lung mucosal inflammation (BR and CF) and may be associated with oral mucosal inflammation (PD). To further determine whether mucosal inflammation functions as a site for induction of RA-AAB and precedes RA, longitudinal studies are necessary in which RA-AAB of specifically the IgA isotype should be assessed in inflamed mucosal tissues and/or in their inflammatory exudates.

No MeSH data available.


Related in: MedlinePlus