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Kastbom, A., Forslind, K., Ernestam, S., Geborek, P., Karlsson, J. A., Petersson, I. F., . . . Lundberg, K. (2016). Changes in the anticitrullinated peptide antibody response in relation to therapeutic outcome in early rheumatoid arthritis: results from the SWEFOT trial. Annals of the Rheumatic Diseases, 75(2), 356-361
Open this publication in new window or tab >>Changes in the anticitrullinated peptide antibody response in relation to therapeutic outcome in early rheumatoid arthritis: results from the SWEFOT trial
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2016 (English)In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 75, no 2, p. 356-361Article in journal (Refereed) Published
Abstract [en]

Objective To determine the relationship between changes in antibody levels towards citrullinated peptides derived from different candidate autoantigens and therapeutic outcome in early rheumatoid arthritis (RA). Methods Baseline and 3-month serum samples from 316 patients with early RA enrolled in the Swedish Farmacotherapy (SWEFOT) trial were analysed for antibodies against cyclic citrullinated peptides (CCP) and citrullinated peptides derived from vimentin (cVim), fibrinogen (cFib) and a-enolase (CEP-1). At 3-month follow-up, methotrexate monotherapy-inadequate responders were randomised to add-on therapy with sulfasalazine and hydroxychloroquine or infliximab. In these patients, anticitrullinated peptide antibodies (ACPA) were also assessed at 12 and 24 months. The proportion of antibody-positive patients and relative changes in antibody levels were compared across ACPA specificities and related to therapeutic response and radiographic progression. Results During the 2-year follow-up, the proportion of patients testing positive declined significantly regarding antibodies to cVim, cFib and CEP-1, while anti-CCP antibody occurrence remained stable over time. Turning anti-cVim antibody negative was most common, and anti-cVim antibody seroreversion during the first three months associated with significantly less 2-year radiographic progression compared with patients who remained positive. Median antibody levels of all tested ACPAs declined uniformly during initial methotrexate therapy and following response to add-on therapy, with no significant relation to treatment regimen or radiographic progression. Conclusions The influence of early antirheumatic therapy on ACPA seroreversions was markedly different across specificities, and early disappearance of anti-cVim antibodies associated with better radiological outcome. Thus, these data suggest that the disappearance of particular ACPA reactivities may be beneficial in early RA.

Place, publisher, year, edition, pages
BMJ PUBLISHING GROUP, 2016
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-125298 (URN)10.1136/annrheumdis-2014-205698 (DOI)000368955700006 ()25550338 (PubMedID)
Note

Funding Agencies|EU [FP7-Health-2010-261460, FP7-Health-2013-306029]; County Council of Ostergotland; Reinhold Sund Foundation; Swedish Society of Medicine; Swedish Rheumatism Association; Thelma Zoegas foundation in Helsingborg; Stiftelsen for Rorelsehindrade i Skane; Swedish Research Council; Strategic Foundations of Sweden (SSF)

Available from: 2016-02-24 Created: 2016-02-19 Last updated: 2017-11-30
Roos, K., Martinsson, K., Ziegelasch, M., Sommarin, Y., Svärd, A., Skogh, T. & Kastbom, A. (2016). Circulating secretory IgA antibodies against cyclic citrullinated peptides in early rheumatoid arthritis associate with inflammatory activity and smoking. Arthritis Research & Therapy, 18(119)
Open this publication in new window or tab >>Circulating secretory IgA antibodies against cyclic citrullinated peptides in early rheumatoid arthritis associate with inflammatory activity and smoking
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2016 (English)In: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 18, no 119Article in journal (Refereed) Published
Abstract [en]

Background: A possible association between mucosal immunization and inflammation, as well as the initiation and propagation of rheumatoid arthritis (RA), is attracting renewed interest. The aim of this study was to evaluate the possible occurrence and clinical correlations of circulating secretory immunoglobulin A (SIgA) antibodies against the second-generation cyclic citrullinated peptides (CCP) among patients with recent-onset RA followed prospectively over 3 years. Methods: Baseline serum samples from 636 patients with recent-onset RA were analyzed for SIgA anti-CCP antibodies by using an enzyme-linked immunosorbent assay with a secondary antibody directed against secretory component. SIgA anti-CCP status at baseline was analyzed in relation to smoking, HLA-DRB1/shared epitope (SE), and the disease course over 3 years. Significant findings were evaluated in regression analysis that included age, sex, smoking, and SE. Results: Seventeen percent of the patients tested positive for circulating SIgA anti-CCP, and the occurrence was confirmed by detection of secretory component in an affinity-purified IgA anti-CCP fraction. SIgA anti-CCP positivity at baseline was associated with slightly higher baseline erythrocyte sedimentation rate (ESR) (mean 38 vs. 31 mm/first hour, p = 0.004) and C-reactive protein (CRP) (mean 30 vs. 23 mg/L, p = 0.047). During follow-up, SIgA anti-CCP-positive patients had a higher mean AUC regarding ESR (adjusted p = 0.003), although there were no significant differences regarding CRP, tender and swollen joint counts, or radiological joint damage (median Larsen progression 1.0 vs. 1.0, p = 0.22). SIgA anti-CCP was associated significantly with smoking (79 % ever smokers among SIgA anti-CCP-positive patients vs. 59 % in SIgA anti-CCP-negative patients, adjusted OR 2.19, 95 % CI 1.01-4.37, p = 0.027) but not with carriage of the SE (80 % vs. 73 %, p = 0.62). Conclusions: Circulating SIgA anti-CCP, which is present in a subgroup of patients with early RA, is not related to SE, but it is environmentally linked to cigarette smoking. This finding strengthens the hypothesis that immunization against citrullinated peptides and/or proteins may occur at mucosal surfaces of the airways. Analysis of SIgA antibodies in serum may be a convenient and more versatile means to investigate the "mucosal connection" in RA compared with analyses in mucosal fluid samples.

Place, publisher, year, edition, pages
BIOMED CENTRAL LTD, 2016
Keywords
Rheumatoid arthritis; Anticitrullinated protein antibodies; Secretory immunoglobulin A; Mucosal immunity
National Category
Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:liu:diva-129493 (URN)10.1186/s13075-016-1014-1 (DOI)000376373100001 ()27215344 (PubMedID)
Note

Funding Agencies|King Gustav Vs 80-year Foundation; Swedish Medical Society; Reinhold Sund Foundation; Ostergotland County Council

Available from: 2016-06-20 Created: 2016-06-20 Last updated: 2017-11-28
Sandin, C., Eriksson, P., Segelmark, M., Skogh, T. & Kastbom, A. (2016). IgA- and SIgA anti-PR3 antibodies in serum versus organ involvement and disease activity in PR3-ANCA associated vasculitis.. Clinical and Experimental Immunology, 184(2), 208-215
Open this publication in new window or tab >>IgA- and SIgA anti-PR3 antibodies in serum versus organ involvement and disease activity in PR3-ANCA associated vasculitis.
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2016 (English)In: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 184, no 2, p. 208-215Article in journal (Refereed) Published
Abstract [en]

Circulating IgA class anti-neutrophil cytoplasm antibodies (ANCA) directed against proteinase 3 (PR3) have been reported in ANCA-associated vasculitis (AAV) with mucosal involvement. However, secretory IgA (SIgA) PR3-ANCA has not been reported previously. In this study we compared serum levels of SIgA PR3-ANCA and IgA PR3-ANCA with IgG PR3-ANCA in relation to disease characteristics. Among 73 patients with AAV and PR3-ANCA at diagnosis, 84% tested positive for IgG PR3-ANCA, 47% for IgA-ANCA and 36% for SIgA PR3-ANCA at the time of sampling for the present study. IgA and IgG PR3-ANCA were similarly represented among patients with different organ manifestations, i.e. upper airway, lung or kidney at time of sampling. However, SIgA PR3-ANCA was significantly less represented among patients with upper airway involvement. During active disease, the proportions of IgA PR3-ANCA and SIgA PR3-ANCA positive patients were significantly higher as compared to inactive disease. Eight patients were prospectively sampled during 24 months from onset of active disease. In these patients, IgA PR3-ANCA and SIgA PR3-ANCA more often turned negative after remission induction as compared to IgG PR3-ANCA. Our findings suggest that serum IgA PR3-ANCA and SIgA PR3-ANCA are more closely related to disease activity in AAV as compared to IgG PR3-ANCA. Further studies are required to reveal if this has implications for disease activity monitoring. The mean number of PR3-ANCA isotypes increased along with disease activity, suggesting a global B-cell activation during active disease. This article is protected by copyright. All rights reserved.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2016
Keywords
ANCA-associated vasculitis; IgA PR3-ANCA; Mucosal immunity; disease activity
National Category
Dermatology and Venereal Diseases
Identifiers
urn:nbn:se:liu:diva-125664 (URN)10.1111/cei.12769 (DOI)000374689500007 ()26762653 (PubMedID)
Note

Funding agencies:  Swedish Society of Medicine; Reinhold Sund foundation for Rheumatology Research; Swedish Association against Rheumatism; Ostergotland County Council

Available from: 2016-02-29 Created: 2016-02-29 Last updated: 2017-11-30
Svärd, A., Skogh, T., Alfredsson, L., Ilar, A., Klareskog, L., Bengtsson, C. & Kastbom, A. (2015). Associations to smoking and shared epitope differ between IgA and IgG class antibodies to cyclic citrullinated peptides in early rheumatoid arthritis. Arthritis & Rheumatology, 67(8), 2032-2037
Open this publication in new window or tab >>Associations to smoking and shared epitope differ between IgA and IgG class antibodies to cyclic citrullinated peptides in early rheumatoid arthritis
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2015 (English)In: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 67, no 8, p. 2032-2037Article in journal (Refereed) Published
Abstract [en]

Background Smoking and HLA-DRB1/shared epitope (SE) are well-known interacting risk factors for developing rheumatoid arthritis (RA) with IgG anticitrullinated protein/peptide antibodies (ACPA). It remains unknown to what extent SE-genes and smoking associate with mucosal immune responses.

Objectives This study was done to explore relations between cigarette smoking habits and SE versus circulating IgA and IgG anti-cyclic citrullinated peptide antibodies (anti-CCP) among early RA patients.

Methods Patients from two early-RA cohorts were analysed, EIRA-1 (n=1663) and TIRA-2 (n=199). The patients were grouped into four subsets based on anti-CCP: IgG-/IgA-, IgG-/IgA+, IgG+/IgA- and IgG+/IgA+. Interaction between smoking and SE was calculated by the attributable proportion due to deviation from additivity. Analyzed controls (n=1100) were randomly selected from the EIRA-1 study base.

Results Anti-CCP occurrence was similar in the two cohorts. Only in EIRA was IgA anti-CCP detected alone in a minority of cases (3%). Smoking was significantly overrepresented among IgA anti-CCP+ patients with or without IgG-class anti-CCP, but not with IgG anti-CCP alone. Presence of SE genes was overrepresented among IgG anti-CCP+ patients with or without IgA-class anti-CCP, but not with IgA anti-CCP alone. Smoking and SE interacted regarding the risk of IgG+/IgA+ RA (AP=0.5, 95 % CI=0.4-0.6), whereas no significant interaction was observed regarding IgG-/IgA+ or IgG+/IgA- RA.

Conclusions Association between cigarette smoking and anti-CCP is limited to cases with IgA-class antibodies in addition to IgG anti-CCP. This suggests a causal relation between chronic mucosal irritation/inflammation, induction of a systemic IgA anti-CCP response and subsequent development of RA.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2015
Keywords
Rheumatoid arthritis, immunoglobulin A, ACPA, smoking, shared epitope
National Category
Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:liu:diva-105986 (URN)10.1002/art.39170 (DOI)000358609300007 ()
Note

At the defence date the status of this publication was Manuscript.

Supported by the Centre for Clinical Research-Dalarna, the Swedish Research Council, the Swedish Association Against Rheumatism, King Gustaf V's 80-Year Foundation, the County Council of Ostergotland, the Reinhold Sund Foundation, the Swedish Society of Medicine, the Medical Research County Council of South-East Sweden, the Swedish Research Council for Health, Working Life, and Welfare, AFA Insurance, the Swedish Rheumatic Foundation, and the Innovative Medicines Initiative (BTCure).

Available from: 2014-04-15 Created: 2014-04-15 Last updated: 2017-12-05Bibliographically approved
Enocsson, H., Sjöwall, C., Wirestam, L., Dahle, C., Kastbom, A., Ronnelid, J., . . . Skogh, T. (2015). Four Anti-dsDNA Antibody Assays in Relation to Systemic Lupus Erythematosus Disease Specificity and Activity. Journal of Rheumatology, 42(5), 817-825
Open this publication in new window or tab >>Four Anti-dsDNA Antibody Assays in Relation to Systemic Lupus Erythematosus Disease Specificity and Activity
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2015 (English)In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 42, no 5, p. 817-825Article in journal (Refereed) Published
Abstract [en]

Objective. Analysis of antibodies against dsDNA is an important diagnostic tool for systemic lupus erythematosus (SLE), and changes in anti-dsDNA antibody levels are also used to assess disease activity. Herein, 4 assays were compared with regard to SLE specificity, sensitivity, and association with disease activity variables. Methods. Cross-sectional sera from 178 patients with SLE, of which 11 were followed consecutively, from a regional Swedish SLE register were analyzed for immunoglobulin G (IgG) anti-dsDNA by bead-based multiplex assay (FIDIS; Theradig), fluoroenzyme-immunoassay (EliA; Phadia/Thermo Fisher Scientific), Crithidia luciliae immunofluorescence test (CLIFT; ImmunoConcepts), and line blot (EUROLINE; Euroimmun). All patients with SLE fulfilled the 1982 American College of Rheumatology and/or the 2012 Systemic Lupus International Collaborating Clinics (SLICC-12) classification criteria. Healthy individuals (n = 100), patients with rheumatoid arthritis (n = 95), and patients with primary Sjogren syndrome (n = 54) served as controls. Results. CLIFT had the highest SLE specificity (98%) whereas EliA had the highest sensitivity (35%). When cutoff levels for FIDIS, EliA, and EUROLINE were adjusted according to SLICC-12 (i.e., double the reference limit when using ELISA), the specificity and sensitivity of FIDIS was comparable to CLIFT. FIDIS and CLIFT also showed the highest concordance (84%). FIDIS performed best regarding association with disease activity in cross-sectional and consecutive samples. Fishers exact test revealed striking differences between methods regarding associations with certain disease phenotypes. Conclusion. CLIFT remains a good choice for diagnostic purposes, but FIDIS performs equally well when the cutoff is adjusted according to SLICC-12. Based on results from cross-sectional and consecutive analyses, FIDIS can also be recommended to monitor disease activity.

Place, publisher, year, edition, pages
Journal of Rheumatology, 2015
Keywords
SYSTEMIC LUPUS ERYTHEMATOSUS; DOUBLE-STRANDED DNA; IMMUNOASSAY; AUTOANTIBODIES; INFLAMMATION; RHEUMATIC DISEASE
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-118866 (URN)10.3899/jrheum.140677 (DOI)000353779400013 ()25684763 (PubMedID)
Note

Funding Agencies|Swedish Research Council [K2012-69X-14594-10-3, K2011-68X-20611-04-3]; Swedish Society for Medicine [SLS-331171]; Swedish Society Against Rheumatism [R-313701, R-307291]; Swedish Society for Medical Research; King Gustaf V 80-year Foundation [FAI2013-0066]; Professor Nanna Svartz foundation

Available from: 2015-06-08 Created: 2015-06-04 Last updated: 2018-11-07
Kastbom, A., Arlestig, L. & Rantapaa-Dahlqvist, S. (2015). Genetic Variants of the NLRP3 Inflammasome Are Associated with Stroke in Patients with Rheumatoid Arthritis. Journal of Rheumatology, 42(10), 1740-1745
Open this publication in new window or tab >>Genetic Variants of the NLRP3 Inflammasome Are Associated with Stroke in Patients with Rheumatoid Arthritis
2015 (English)In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 42, no 10, p. 1740-1745Article in journal (Refereed) Published
Abstract [en]

Objective. Inflammasomes are intracellular protein complexes important for the production of proinflammatory cytokines. Studies have suggested that the NLRP3 inflammasome influences both the severity of rheumatoid arthritis (RA) and development of atherosclerosis. Therefore, we investigated whether functional genetic variants related to the NLRP3 inflammasome influence the risk of cardiovascular (CV) disease (CVD) in patients with RA. Methods. The incidence of CVD was assessed in 522 patients with established RA by a retrospective survey of medical records in combination with a 6-year prospective followup. NLRP3-Q705K and CARD8-C10X genotypes were analyzed in relation to CVD by logistic regression, adjusting for traditional risk factors, antirheumatic treatment, and age at the onset of RA. Results. Carriage of the NLRP3-Q705K minor allele was associated with an increased risk of stroke/transient ischemic attack (TIA; OR 2.01, 95% CI 1.0-4.1, p = 0.05), while CARD8-C10X was not associated with any type of CV event. Patients with greater than= 1 variant allele in both polymorphisms had an increased risk of CVD when compared with patients without variant alleles present in both polymorphisms (adjusted OR 3.05, 95% CI 1.42-6.54, p = 0.004). Stratification showed that this risk was confined to stroke/TIA (adjusted OR 5.09, 95% CI 2.27-11.44, p less than 0.0001) and not to myocardial infarction (MI)/angina pectoris (adjusted OR 1.58, 95% CI 0.67-3.73). Risk estimates were consistently higher among female patients. Conclusion. Genetic variants of the NLRP3 inflammasome influence the risk of stroke/TIA, but not of MI/angina pectoris in Swedish patients with established RA.

Place, publisher, year, edition, pages
J RHEUMATOL PUBL CO, 2015
Keywords
RHEUMATOID ARTHRITIS; INFLAMMASOMES; GENETICS; CARDIOVASCULAR DISEASE
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-122433 (URN)10.3899/jrheum.141529 (DOI)000362234900004 ()26178285 (PubMedID)
Note

Funding Agencies|County Council of Ostergotland; Reinhold Sund Foundation; Swedish Society of Medicine; Swedish Research Council [K2011-68X-20611-04-3, Dnr 825-2010-5986]; King Gustaf Vs 80-Year Fund; King Gustaf Vs and Queen Victorias Fund; Swedish Rheumatism Association; Swedish COMBINE program; Vasterbotten county council; Swedish Foundation for Strategic Research

Available from: 2015-11-03 Created: 2015-11-02 Last updated: 2017-12-01
Enocsson, H., Sjöwall, C., Kastbom, A., Skogh, T., Eloranta, M.-L., Rönnblom, L. & Wetterö, J. (2014). Association of Serum C-Reactive Protein Levels With Lupus Disease Activity in the Absence of Measurable Interferon-α and a C-Reactive Protein Gene Variant. Arthritis & rheumatology (Hoboken, N.J.), 66(6), 1568-1573
Open this publication in new window or tab >>Association of Serum C-Reactive Protein Levels With Lupus Disease Activity in the Absence of Measurable Interferon-α and a C-Reactive Protein Gene Variant
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2014 (English)In: Arthritis & rheumatology (Hoboken, N.J.), ISSN 2326-5191, Vol. 66, no 6, p. 1568-1573Article in journal (Refereed) Published
Abstract [en]

Objectives: The type I interferon (IFN) system is important in the pathogenesis of systemic lupus erythematosus (SLE). We previously demonstrated an inhibitory effect of IFNα on interleukin 6 (IL-6) induced C-reactive protein (CRP) in vitro, hypothetically explaining the poor correlation between disease activity and CRP levels in SLE. Herein we investigated disease activity, IL-6 and CRP in relation to a CRP gene polymorphism and IFN.

Methods: Sera from 155 SLE patients and 100 controls were analyzed for CRP. Patients were genotyped for a CRP single nucleotide polymorphism (rs1205) associated with low CRP levels. Serum IFNα and IL-6 was quantified by immunoassays. Clinical disease activity was assessed by SLE disease activity index 2000 (SLEDAI-2K).

Results: CRP levels were increased in SLE patients compared to controls, but were not associated with SLEDAI-2K or IL-6 levels. However, exclusion of patients carrying at least one rs1205 minor allele revealed an association between disease activity and CRP levels (p=0.005). We found a strong association between disease activity and CRP levels (p<0.0005) when patients with measurable IFNα as well as the minor allele of rs1205 where excluded from the analysis. Similarly, when patients with raised IFNα and/or the rs1205 polymorphism were excluded, IL-6 associated with CRP levels.

Conclusions: The present study demonstrates that serum IFNα as well as CRP genotype affects the CRP response in SLE patients. Lack of correlation between serum levels of CRP and disease activity could therefore be explained by activation of the type I IFN system and polymorphisms in the CRP gene. © 2014 American College of Rheumatology.

Place, publisher, year, edition, pages
Hoboken, NJ, United States: John Wiley & Sons, 2014
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-105501 (URN)10.1002/art.38408 (DOI)000337366200018 ()24574329 (PubMedID)
Available from: 2014-03-25 Created: 2014-03-25 Last updated: 2015-08-31Bibliographically approved
Frodlund, M., Dahlström, Ö., Kastbom, A., Skogh, T. & Sjöwall, C. (2013). Associations between antinuclear antibody staining patterns and clinical features of systemic lupus erythematosus: analysis of a regional Swedish register. Paper presented at 10th International Congress on SLE- Lupus 2013, 18-21 April 2013, Buenos Aires, Argentina. BMJ Open, 3, 1-8
Open this publication in new window or tab >>Associations between antinuclear antibody staining patterns and clinical features of systemic lupus erythematosus: analysis of a regional Swedish register
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2013 (English)In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 3, p. 1-8Article in journal (Refereed) Published
Abstract [en]

Objective Antinuclear antibody (ANA) analysis by immunofluorescence (IF) microscopy remains a diagnostic hallmark of systemic lupus erythematosus (SLE). The clinical relevance of ANA fine-specificities in SLE has been addressed repeatedly, whereas studies on IF-ANA staining patterns in relation to disease manifestations are very scarce. This study was performed to elucidate whether different staining patterns associate with distinct SLE phenotypes.

Design Observational cohort study.

Setting One university hospital rheumatology unit in Sweden.

Participants The study population consisted of 222 cases (89% women; 93% Caucasians), where of 178 met ≥4/11 of the 1982 American College of Rheumatology (ACR-82) criteria. The remaining 20% had an SLE diagnosis based on positive IF-ANA (HEp-2 cells) and ≥2 typical organ manifestations at the time of diagnosis (Fries’ criteria).

Outcome measures The IF-ANA staining patterns homogenous (H-ANA), speckled (S-ANA), combined homogenous and speckled (HS-ANA), centromeric (C-ANA), nucleolar (N-ANA)±other patterns and other nuclear patterns (oANA) were related to disease manifestations and laboratory measures. Antigen-specificities were also considered regarding double-stranded DNA (Crithidia luciliae) and the following extractable nuclear antigens: Ro/SSA, La/SSB, Smith antigen (Sm), small nuclear RNP (snRNP), Scl-70 and Jo-1 (immunodiffusion and/or line-blot technique).

Results 54% of the patients with SLE displayed H-ANA, 22% S-ANA, 11% HS-ANA, 9% N-ANA, 1% C-ANA, 2% oANA and 1% were never IF-ANA positive. Staining patterns among patients meeting Fries’ criteria alone did not differ from those fulfilling ACR-82. H-ANA was significantly associated with the 10th criterion according to ACR-82 (‘immunological disorder’). S-ANA was inversely associated with arthritis, ‘immunological disorder’ and signs of organ damage.

Conclusions H-ANA is the dominant IF-ANA pattern among Swedish patients with SLE, and was found to associate with ‘immunological disorder’ according to ACR-82. The second most common pattern, S-ANA, associated negatively with arthritis and organ damage.

National Category
Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:liu:diva-91381 (URN)10.1136/bmjopen-2013-003608 (DOI)000326882800019 ()
Conference
10th International Congress on SLE- Lupus 2013, 18-21 April 2013, Buenos Aires, Argentina
Available from: 2013-04-23 Created: 2013-04-23 Last updated: 2019-02-11
Kastbom, A., Klingberg, E., Verma, D., Carlsten, H., Forsblad-dElia, H., Wesamaa, J., . . . Söderkvist, P. (2013). Genetic variants in CARD8 but not in NLRP3 are associated with ankylosing spondylitis. Scandinavian Journal of Rheumatology, 42(6), 465-468
Open this publication in new window or tab >>Genetic variants in CARD8 but not in NLRP3 are associated with ankylosing spondylitis
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2013 (English)In: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 42, no 6, p. 465-468Article in journal (Refereed) Published
Abstract [en]

Objectives: The NOD-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome is important for interleukin-1beta (IL-1 beta) processing as part of an innate immune response. Caspase recruitment domain family, member 8 (CARD8) is an inhibitor of nuclear factor kappa B (NF-kappa B) and possibly also a part of the NLRP3 inflammasome. The objective of this study was to evaluate one single nucleotide polymorphism (SNP) in CARD8 and three SNPs in NLRP3 in ankylosing spondylitis (AS) susceptibility and disease phenotype. less thanbrgreater than less thanbrgreater thanMethod: We recruited 492 AS patients from Southern Sweden fulfilling the modified New York criteria for AS, and assessed phenotypic characteristics from medical records and questionnaires. Patients with psoriasis or clinically overt inflammatory bowel disease (IBD) were excluded, as were patients without human leucocyte antigen B27 (HLA-B27). Three NLRP3 SNPs (rs35829419, rs4353135, and rs10733113) and one SNP in CARD8 (rs2043211) were genotyped by commercially available TaqMan assays, and the results compared at genotype and allele levels to those of 793 population-based controls. In a subgroup of the patients (n = 169), faecal calprotectin was assessed as a marker of subclinical intestinal inflammation. less thanbrgreater than less thanbrgreater thanResults: The minor allele (A) of CARD8-C10X (rs2043211) was associated with a decreased risk of AS in a dominant model [odds ratio (OR) 0.74, 95% confidence interval (CI) 0.54-0.94, p = 0.012] and at the allelic level (OR 0.81, 95% CI 0.68-0.97, p = 0.02), but was not associated with levels of faecal calprotectin. There was no association regarding NLRP3 SNPs and AS susceptibility, and none of the investigated SNPs were associated with iritis, anti-tumour necrosis factor (anti-TNF) therapy, or peripheral joint involvement. less thanbrgreater than less thanbrgreater thanConclusion: In a Swedish population, the minor allele of CARD8-C10X is associated with a decreased risk of AS, but not with levels of faecal calprotectin or disease phenotype.

Place, publisher, year, edition, pages
Informa Healthcare, 2013
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-102509 (URN)10.3109/03009742.2013.779020 (DOI)000327259200007 ()
Note

Funding Agencies|Medical Research Council of Southeast Sweden (FORSS)|FORSS-88721|County Council of Ostergotland||

Available from: 2013-12-12 Created: 2013-12-12 Last updated: 2017-12-06
Svärd, A., Kastbom, A., Sommarin, Y. & Skogh, T. (2013). Salivary IgA antibodies to cyclic citrullinated peptides (CCP) in rheumatoid arthritis. Immunobiology, 218(2), 232-237
Open this publication in new window or tab >>Salivary IgA antibodies to cyclic citrullinated peptides (CCP) in rheumatoid arthritis
2013 (English)In: Immunobiology, ISSN 0171-2985, E-ISSN 1878-3279, Vol. 218, no 2, p. 232-237Article in journal (Refereed) Published
Abstract [en]

Circulating IgG anti-cyclic citrullinated peptide antibodies (CCP) are highly specific for rheumatoid arthritis (RA) and prognostic of poor outcome. Serum IgA anti-CCP occurs in a subset of IgG-positive cases and relates to still more aggressive disease. Mucosal IgA-class antibodies, however, are generally associated with anti-inflammatory actions and systemic tolerance induction. In the present study, unstimulated salivary samples from 63 patients with established RA and 20 healthy persons were analysed by enzyme-linked immunoassay for the presence of IgA anti-CCP antibodies. To ensure antigen specificity, IgA-reactivity with the corresponding uncitrullinated antigen, cyclic arginine peptide (CAP), was analysed and anti-CCP/anti-CAP ratios calculated. Retrospective data regarding disease activity and radiological outcome were achieved via medical records. Salivary IgA anti-CCP was found in 14/63 (22%) patients and one (5%) control (positive test = anti-CCP/anti-CAP ratio andgt; 1.5). Salivary IgA reactivity was dose-dependently inhibited by pre-incubation with soluble CCP to a degree strongly correlating with anti-CCP/anti-CAP ratio. In salivary IgA anti-CCP positive patients, joint erosions within 6 years of diagnosis was significantly lower (p = 0.043), and at the time for diagnosis there was a trend towards lower erythrocyte sedimentation rate (p = 0.071) and C-reactive protein (p = 0.085). Contrasting to circulating IgG and IgA anti-CCP, our results imply that salivary IgA antibodies may be associated with a less severe outcome of RA. Hypothetically, this relates to an anti-inflammatory and protective immunomodulating role of secretory IgA-class autoantibodies against citrullinated antigens presented at mucosal surfaces.

Place, publisher, year, edition, pages
Elsevier, 2013
Keywords
Citrullinated peptides, IgA, Rheumatoid arthritis, Saliva, Mucosal immunity
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-90205 (URN)10.1016/j.imbio.2012.04.011 (DOI)000315312000013 ()
Note

Funding Agencies|Centre for Clinical Research in Dalarna||Swedish Research Council|2008-2832|Swedish Association Against Rheumatism||King Gustaf Vth 80-Year Foundation||County Council of Ostergotland Research Foundations||Medical Research County Council of South-East Sweden (FORSS)||

Available from: 2013-03-21 Created: 2013-03-21 Last updated: 2017-12-06
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