| 1. |
- Innala, Lena, et al.
(författare)
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Antibodies against mutated citrullinated vimentin are a better predictor of disease activity at 24 months in early rheumatoid arthritis than antibodies against cyclic citrullinated peptides
- 2008
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Ingår i: Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 35:6, s. 1002-1008
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To evaluate the predictive values for disease progression of various antibodies against citrullinated peptide proteins (ACPA) and their relation to PTPN22 1858C/T polymorphism and HLA-DRB1 alleles in early rheumatoid arthritis (RA).METHODS: The ACPA, e.g., antibodies against mutated citrullinated vimentin (MCV), cyclic citrullinated peptides (CCP) type 2 and 3 (both of IgG isotype) and 3.1 (of both IgG and IgA isotypes), were analyzed at baseline in patients with early RA (n = 210) and in population controls (n = 102) using an enzyme immunoassay. A receiver-operating characteristic curve was constructed for each antibody. Disease activity [swollen and tender joints, visual analog scale for global health, and erythrocyte sedimentation rate (ESR)] was evaluated at baseline and regularly for 24 months. Radiographs of hands and feet were graded using the Larsen score.RESULTS: Patients with anti-MCV antibodies had significantly less reduction in Disease Activity Score (DAS28) over time (p < 0.01), and significantly increased area under the curve (AUC) for DAS28 (p < 0.05), ESR (p < 0.01), C-reactive protein (p < 0.01), and swollen joint count (p = 0.057) compared to those without. Corresponding differences were not found in patients with anti-CCP2, CCP3, and CCP3.1 antibodies. Radiological progression (p < 0.0001-0.01) and radiological outcome (p < 0.0001-0.01) at 24 months were significantly predicted by all ACPA after baseline adjustments. PTPN22 T variant and HLA-DRB1 alleles were not related to radiological progression or inflammatory activity over time.CONCLUSION: Anti-MCV antibodies are associated with a more severe RA disease, as measured by DAS28, ESR, and swollen joint count over time, compared with anti-CCP2, CCP3, and CCP3.1 antibodies. Radiological progression was predicted equally by all 4 autoantibodies.
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| 2. |
- Berglin, Ewa, MD, PhD, 1955-, et al.
(författare)
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Radiological outcome in rheumatoid arthritis is predicted by presence of antibodies against cyclic citrullinated peptide before and at disease onset, and by IgA-RF at disease onset
- 2006
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 65:4, s. 453-458
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To evaluate the significance of antibodies against cyclic citrullinated peptide (anti-CCP) and rheumatoid factors (RFs), before the onset of rheumatoid arthritis and when presenting as early disease (baseline), for disease activity and progression. METHODS: 93 of a cohort of 138 patients with early rheumatoid arthritis (<12 months of symptoms) had donated blood before symptoms of rheumatoid arthritis (defined as pre-patients) and were identified from among blood donors within the Medical Biobank of northern Sweden. Disease activity (erythrocyte sedimentation rate (ESR), C reactive protein, joint score, global visual analogue scale) and radiological destruction in hands and feet (Larsen score) were assessed at baseline and after two years. Anti-CCP antibodies and RFs were analysed using enzyme immunoassays. HLA shared epitope (SE) alleles (DRB1*0401/0404) were identified. RESULTS: Patients with anti-CCP antibodies before disease onset had significantly higher Larsen score at baseline and after two years. In multiple regression analyses baseline values of anti-CCP/IgA-RF/IgG-RF/IgM-RF, swollen joint count, and Larsen score significantly predicted radiological outcome at two years. In logistic regression analyses, baseline values of anti-CCP antibodies/IgA-RF, therapeutic response at six months, and swollen joint count/ESR significantly predicted radiological progression after two years. The baseline titre of anti-CCP antibodies was higher in patients with radiological progression and decreased significantly in those with response to therapy. SE allele carriage was associated with a positive test for anti-CCP antibodies in pre-patients and in early rheumatoid arthritis. CONCLUSIONS: Presence of anti-CCP antibodies before disease onset is associated with more severe radiological damage. The titre of anti-CCP antibodies is related to disease severity.
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| 3. |
- Alenius, Gerd-Marie, et al.
(författare)
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Disease manifestations and HLA antigens in psoriatic arthritis in northern Sweden
- 2002
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Ingår i: Clinical Rheumatology. - : Springer Science and Business Media LLC. - 0770-3198 .- 1434-9949. ; 21:5, s. 357-362
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to identify potential markers of aggressive joint manifestations and HLA associations in patients with psoriatic arthritis (PsA) in northern Sweden. Patients with PsA were examined clinically, with laboratory tests and radiologically. The classification of the disease was based on peripheral and/or axial engagement. HLA B17, B37 and B62 were significantly increased in PsA patients. Univariate analyses suggest that the HLA antigens B37, B62 and some clinical variables were associated with disease course. However, in multivariate analyses distal interphalangeal joint affliction and polyarticular manifestations were the only variables remaining significantly associated with irreversible joint destruction or deformity. There were no significant effects of HLA antigens. In this cross-sectional study, clinical manifestations were more reliable predictors of aggressive joint damage than were specific HLA antigens. However, HLA antigens seemed to modify the expression of the joint disease rather than being involved in joint disease susceptibility.
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| 4. |
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| 5. |
- Kokkonen, Heidi, et al.
(författare)
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The PTPN22 1858C/T polymorphism is associated with anti-cyclic citrullinated peptide antibody-positive early rheumatoid arthritis in northern Sweden
- 2007
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Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6362 .- 1478-6354. ; 9:5, s. 403-
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Tidskriftsartikel (refereegranskat)abstract
- The PTPN22 1858C/T polymorphism has been associated with several autoimmune diseases including rheumatoid arthritis (RA). We have shown that carriage of the T variant (CT or TT) of PTPN22 in combination with anti-cyclic citrullinated peptide (anti-CCP) antibodies highly increases the odds ratio for developing RA. In the present study we analysed the association between the PTPN22 1858C/T polymorphism and early RA in patients from northern Sweden, related the polymorphism to autoantibodies and the HLA-DR shared epitope, and analysed their association with markers for disease activity and progression. The inception cohort includes individuals who also donated samples before disease onset. A case-control study was performed in patients (n = 505; 342 females and 163 males) with early RA (mean duration of symptoms = 6.3 months) and in population-based matched controls (n = 970) from northern Sweden. Genotyping of the PTPN22 1858C/T polymorphism was performed using a TaqMan instrument. HLA-shared epitope alleles were identified using PCR sequence-specific primers. Anti-CCP2 antibodies were determined using enzyme-linked immunoassays. Disease activity (that is, the number of swollen and tender joints, the global visual analogue scale, and the erythrocyte sedimentation rate) was followed on a regular basis (that is, at baseline and after 6, 12, 18 and 24 months). Both the 1858T allele and the carriage of T were associated with RA (chi2 = 23.84, P = 0.000001, odds ratio = 1.69, 95% confidence interval = 1.36-2.11; and chi2 = 22.68, P = 0.000002, odds ratio = 1.79, 95% confidence interval = 1.40-2.29, respectively). Association of the 1858T variant with RA was confined to seropositive disease. Carriage of 1858T and the presence of anti-CCP antibodies was independently associated with disease onset at an earlier age (P < 0.05 and P < 0.01, respectively), while the combination of both resulted in an even earlier age at onset. Smoking was identified as a risk factor independent of the 1858T variant and anti-CCP antibodies.
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| 6. |
- Lagerqvist, Carina, et al.
(författare)
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Antigliadin immunoglobulin A best in finding celiac disease in children younger than 18 months of age
- 2008
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Ingår i: Journal of Pediatric Gastroenterology and Nutrition - JPGN. - 0277-2116 .- 1536-4801. ; 47:4, s. 428-35
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The aim was to investigate age-dependent serum levels and occurrence of elevated celiac disease (CD)-related antibodies in young children, to define the optimal serological procedure when selecting for small intestinal biopsy. PATIENTS AND METHODS: Included were 428 children with biopsy verified CD (median age 16 months; range 7.5 months-14 years) and 216 controls (median age 2.7 years; range 8.5 months-14.6 years). Immunoglobulin (Ig) A antibodies against gliadin (AGA-IgA), tissue transglutaminase (tTG-IgA), and endomysium (EMA-IgA) were analysed. RESULTS: Increased serum AGA-IgA levels were found in 411 of 428 CD cases, tTG-IgA in 385 of 428, and EMA-IgA in 383 of 428. In the control group, 11 of 216 had increased levels of AGA-IgA, 5 of 216 of tTG-IgA, and 8 of 216 of EMA-IgA. In CD children younger than 18 months, elevated AGA-IgA occurred in 97% and elevated tTG-IgA and EMA-IgA were found in 83% of the cases. Conversely, in CD children older than 18 months, elevated AGA-IgA occurred in 94%, and elevated tTG-IgA and EMA-IgA were found in 99% of the cases. CONCLUSIONS: In children older than 18 months, both tTG-IgA and EMA-IgA are sufficiently accurate to be used as a single antibody marker, whereas a large proportion of younger children with CD lack these antibodies. Therefore, when selecting children for small intestinal biopsy, the detection of a combination of AGA-IgA and tTG-IgA is optimal for identifying untreated CD in children younger than 18 months.
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| 7. |
- Sundström, Peter, et al.
(författare)
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EBNA-1 reactivity and HLA DRB1*1501 as statistically independent risk factors for multiple sclerosis : a case-control study
- 2008
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Ingår i: Multiple Sclerosis Journal. - Basingstoke : Stockton. - 1352-4585 .- 1477-0970. ; 14:8, s. 1120-1122
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Tidskriftsartikel (refereegranskat)abstract
- Objectives and methods: The interaction between the two best documented risk factors (human leukocyte antigen [HLA] class II [DRB1*1501 positivity] and Epstein-Barr virus [elevated Epstein-Barr nuclear antigen 1 (EBNA-1) antibody reactivity]) for multiple sclerosis (MS) was studied in a case-control study of biobank samples from 109 MS cases and 212 matched referents. Results: Multivariate logistic regression analysis showed that both were statistically significant in both sexes. HLA DRB1*1501-positive referents had higher EBNA-1 reactivity than HLA-negative referents. Less EBNA-1 reactivity was required to increase the MS risk in HLA DRB1*1501-positives than in HLA-negatives. Conclusion: We suggest that HLA DRB1*1501-positive individuals have an increased vulnerability to EBV-induced autoimmunity.
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