Lars Klareskog

Karolinska University Hospital, Tukholma, Stockholm, Sweden

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Publications (623)4278.91 Total impact

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    ABSTRACT: The presence of a new autoantibody system, anti-carbamylated protein (anti-CarP) antibodies, has been identified in rheumatoid arthritis (RA). The presence of anti-CarP antibodies was evaluated in samples taken from individuals who subsequently developed RA before and after onset of symptoms and related to previously analysed antibodies against citrullinated peptides (ACPA specificities) and anti-CCP2. A total of 252 individuals, with 423 samples from before onset of symptoms of RA, and 197 population controls were identified as donors to the Medical Biobank of Northern Sweden; 192 of them were also sampled at the time of diagnosis. All samples were analysed for anti-CarP IgG and anti-CCP2 antibodies using ELISAs. Ten different antibody reactivities against citrullinated antigens (ACPA specificities) were analysed using a custom-made microarray based on the ImmunoCAP ISAC system (Phadia). The concentration of anti-CarP antibodies was significantly increased in the pre-symptomatic individuals compared with controls (P <0.001) and also increased significantly after disease onset (P <0.001). The sensitivity for anti-CarP antibodies in the pre-symptomatic individuals was 13.9% (95% CI: 11 to 17.6) and 42.2% (95% CI: 35.4 to 49.3) following development of RA. Anti-CarP antibody positivity was found in 5.1% to 13.3% of individuals negative for anti-CCP2 or ACPA specificities. Presence of anti-CarP antibodies was significantly related to radiological destruction at baseline, at 24 months and also to radiological change (P <0.05, all). The results indicate that anti-CarP antibodies are associated with disease development, even after adjusting for the presence of different ACPA fine specificities, and in anti-CCP2 negative individuals and contribute to the identification of a subset of patients with worse radiological progression of the disease independent of ACPA.
    Arthritis Research & Therapy 12/2015; 17(1). DOI:10.1186/s13075-015-0536-2 · 4.12 Impact Factor
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    ABSTRACT: Immunglobulin G (IgG) sialylation represents a key checkpoint that determines the engagement of pro- or anti-inflammatory Fcγ receptors (FcγR) and the direction of the immune response. Whether IgG sialylation influences osteoclast differentiation and subsequently bone architecture has not been determined yet, but may represent an important link between immune activation and bone loss. Here we demonstrate that desialylated, but not sialylated, immune complexes enhance osteoclastogenesis in vitro and in vivo. Furthermore, we find that the Fc sialylation state of random IgG and specific IgG autoantibodies determines bone architecture in patients with rheumatoid arthritis. In accordance with these findings, mice treated with the sialic acid precursor N-acetylmannosamine (ManNAc), which results in increased IgG sialylation, are less susceptible to inflammatory bone loss. Taken together, our findings provide a novel mechanism by which immune responses influence the human skeleton and an innovative treatment approach to inhibit immune-mediated bone loss.
    Nature Communications 03/2015; 6:6651. DOI:10.1038/ncomms7651 · 10.74 Impact Factor
  • Lars Klareskog, Anca I Catrina
    Nature Reviews Rheumatology 03/2015; DOI:10.1038/nrrheum.2015.38 · 10.25 Impact Factor
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    ABSTRACT: To study the association between postmenopausal hormone therapy (PMH) use and the risk of rheumatoid arthritis (RA) stratifying the cases by the presence/absence of antibodies against citrullinated peptides (ACPA). A subset of the Epidemiological Investigation of RA (EIRA), a population-based case-control study, comprising postmenopausal women aged 50-70 living in Sweden, between 2006 and 2011 was analysed (523 cases and 1057 controls). All participants answered an extensive questionnaire, including questions regarding PMH use and potential confounders (education, smoking, BMI, oral contraceptives, reproductive factors). We calculated odds ratios (OR) of developing ACPA-positive/-negative RA, with 95 % confidence intervals (CI) and adjusted for age, residential area and smoking. Current users of PMH had a decreased risk of ACPA-positive RA compared with never users (OR 0.6, 95 % CI 0.3-0.9). The decreased risk was observed mainly in the age-group 50-59 years (OR 0.3, 95 % CI 0.1-0.8) but not in the age-group 60-70 years (OR 0.8, 95 % CI 0.4-1.4). Among current users of a combined therapy (estrogen plus progestogens) an OR of 0.3 (95 % CI 0.1-0.7) of ACPA-positive RA was observed, while no significant association was found among women who used estrogen only (OR 0.8, 95 % CI 0.5-1.6). No association between PMH use and ACPA-negative RA was found. PMH use might reduce the risk of ACPA-positive RA in post-menopausal women over 50 years of age, but not of ACPA-negative RA. The negative influence of this treatment on the risk of other chronic conditions cannot be overlooked.
    European Journal of Epidemiology 03/2015; DOI:10.1007/s10654-015-0004-y · 5.15 Impact Factor
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    ABSTRACT: The Structural Genomics Consortium (SGC) and its clinical, industry and disease-foundation partners are launching open-source preclinical translational medicine studies.
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    ABSTRACT: We performed gene-gene interaction analysis, with HLA-DRB1 shared epitope (SE) alleles for 195 SNPs within immunologically important MAP2Ks, MAP3Ks and MAP4Ks gene families, in 2010 rheumatoid arthritis (RA) patients and 2280 healthy controls. We found a significant statistical interaction for rs10468473 with SE in autoantibody-positive RA. Individuals heterozygous for rs10468473 demonstrated higher expression of total MAP2K4 mRNA in blood, compared to A-allele homozygous. We discovered a novel, putatively translated, "cassette exon" RNA splice form of MAP2K4, differentially expressed in peripheral blood mononuclear cells from 88 RA cases and controls. Within the group of RA patients, we observed a correlation of MAP2K4 isoform expression with carried SE alleles, autoantibody, and rheumatoid factor profiles. αTNF-dependent modulation of isoform expression pattern was detected in the Jurkat cell line. Our data suggest a genetic interaction between MAP2K4 and HLA-DRB1, and the importance of rs10468473 and MAP2K4 splice variants in the development of autoantibody-positive RA. Copyright © 2015. Published by Elsevier Inc.
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    ABSTRACT: Do recent infections affect the risk of rheumatoid arthritis (RA)? We used the population-based case-control study EIRA (N=6401) on incident RA and healthy controls, matched for sex, age, calendar period and area of residence. Gastroenteritis, urinary tract infection, genital infection, prostatitis, sinusitis, tonsillitis and pneumonia during the 2 years before inclusion in the study were investigated. Conditional logistic regression was used to calculate OR, adjusting for smoking and socioeconomic status. Infections in the gastrointestinal and urogenital tract before clinical onset were associated with a lowered risk of RA: gastroenteritis (OR=0.71 (95% CI 0.63 to 0.80)), urinary tract infections (OR=0.78 (95% CI 0.68 to 0.90)) and genital infections (OR=0.80 (95% CI 0.64 to 1.00)), while a non-significant association of similar magnitude was observed for the less common prostatitis (OR=0.64 (95% CI 0.38 to 1.08)). In contrast, no associations were observed for sinusitis, tonsillitis or pneumonia. Gastrointestinal and urogenital infections, but not respiratory infections, are associated with a significantly lowered risk of RA. The results indicate that infections in general do not affect the risk for RA, but that certain infections, hypothetically associated with changes in the gut microbiome, could diminish the risk. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to
    Annals of the Rheumatic Diseases 02/2015; 74(5). DOI:10.1136/annrheumdis-2014-206493 · 9.27 Impact Factor
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    ABSTRACT: Objective Family history of rheumatoid arthritis (RA) is one of the strongest risk factors for developing RA, and information on family history is, therefore, routinely collected in clinical practice. However, as more genetic and environmental risk factors shared by relatives are identified, the importance of family history may diminish. The aim of this study was to determine how much of the familial risk of RA can be explained by established genetic and nongenetic risk factors.Methods History of RA among first-degree relatives of individuals in the Epidemiological Investigation of Rheumatoid Arthritis case-control study was assessed through linkage to the Swedish Multigeneration Register and the Swedish Patient Register. We used logistic regression models to investigate the decrease in familial risk after successive adjustment for combinations of nongenetic risk factors (smoking, alcohol intake, parity, silica exposure, body mass index, fatty fish consumption, and education), and genetic risk factors (shared epitope [SE] and 76 single-nucleotide polymorphisms [SNPs]).ResultsEstablished nongenetic risk factors did not explain familial risk of either seropositive or seronegative RA to any significant degree. Genetic risk factors accounted for a limited proportion of the familial risk of seropositive RA (unadjusted odds ratio [OR] 4.10, SE-adjusted OR 3.72, SNP-adjusted OR 3.46, and SE and SNP-adjusted OR 3.35).Conclusion Established risk factors only provided an explanation for familial risk of RA in minor part, suggesting that many (familial) risk factors remain to be identified, in particular for seronegative RA. Family history of RA therefore remains an important clinical risk factor for RA, the value of which has not yet been superseded by other information. There is thus a need for further etiologic studies of both seropositive and seronegative RA.
    01/2015; 67(2):352-362. DOI:10.1002/art.38927
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    ABSTRACT: 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). 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 α-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. 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. 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. WHO database at the Karolinska institute: CT20080004; and NCT00764725. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to
    Annals of the Rheumatic Diseases 12/2014; DOI:10.1136/annrheumdis-2014-205698 · 9.27 Impact Factor
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    ABSTRACT: Objectives Our objective was to estimate the risk of developing rheumatoid arthritis (RA) associated with a family history of non-RA arthritis-related diseases. This familial co-aggregation is of clinical interest since it is often encountered when assessing family history of RA specifically, but also informative on the genetic overlap between these diseases. Since anticitrullinated peptide antibodies/rheumatoid factor (RF)-positive and RF-negative RA have both specific and shared genetic factors, the familial co-aggregation was assessed separately for seropositive and seronegative disease.Methods Nested case-control study in prospectively recorded Swedish total population data. The Multi-Generation Register identified first-degree relatives. RA and arthritis-related diseases were ascertained through the nationwide patient register. RA serology was based on International Classification of Diseases tenth revision coded diagnoses, mainly reflecting RF. Familial risks were calculated using conditional logistic regression. Results were replicated using the Swedish rheumatology register.Results Familial co-aggregation was found between RA and every studied arthritis-related disease, but the magnitude varied widely, from juvenile idiopathic arthritis (JIA) (seropositive RA OR=3.98 (3.01 to 5.26); seronegative RA OR=5.70 (3.47 to 9.36)) to osteoarthritis (seropositive RA OR=1.03 (1.00 to 1.06); seronegative RA OR=1.05 (1.00 to 1.09)). The familial co-aggregation pattern of non-RA arthritis-related diseases was overall similar for seropositive and seronegative RA. Among those with family history of RA, relatives’ other arthritis-related diseases conferred little or no additional risk.Conclusions Although family history of several arthritis-related diseases may be useful to predict RA (eg, lupus and JIA), others (eg, osteoarthritis and arthralgia) are less useful. Seropositive and seronegative RA had rather similar familial co-aggregation patterns with arthritis-related diseases, suggesting that the two RA subsets are similar in the genetic factors that overlap with these diseases.
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    ABSTRACT: The Fc-glycan profile of IgG1 anti-citrullinated peptide antibodies (ACPA) in rheumatoid arthritis (RA) patients has recently been reported to be different from non-ACPA IgG1, a phenomenon which likely plays a role in RA pathogenesis. Herein we investigate the Fc-glycosylation pattern of all ACPA-IgG isotypes and simultaneously investigate in detail the IgG protein-chain sequence repertoire. IgG from serum or plasma (S/P, n = 14) and synovial fluid (SF, n = 4) from 18 ACPA-positive RA-patients was enriched using Protein G columns followed by ACPA-purification on cyclic citrullinated peptide-2 (CCP2)-coupled columns. Paired ACPA (anti-CCP2 eluted IgG) and IgG flow through (FT) fractions were analyzed by LC-MS/MS-proteomics. IgG peptides, isotypes and corresponding Fc-glycopeptides were quantified and interrogated using uni- and multivariate statistics. The Fc-glycans from the IgG4 peptide EEQFNSTYR was validated using protein A column purification. Relative to FT-IgG4, the ACPA-IgG4 Fc-glycan-profile contained lower amounts (p = 0.002) of the agalacto and asialylated core-fucosylated biantennary form (FA2) and higher content (p = 0.001) of sialylated glycans. Novel differences in the Fc-glycan-profile of ACPA-IgG1 compared to FT-IgG1 were observed in the distribution of bisected forms (n = 5, p = 0.0001, decrease) and mono-antennnary forms (n = 3, p = 0.02, increase). Our study also confirmed higher abundance of FA2 (p = 0.002) and lower abundance of afucosylated forms (n = 4, p = 0.001) in ACPA-IgG1 relative to FT-IgG1 as well as lower content of IgG2 (p = 0.0000001) and elevated content of IgG4 (p = 0.004) in ACPA compared to FT. One λ-variable peptide sequence was significantly increased in ACPA (p = 0.0001). In conclusion, the Fc-glycan profile of both ACPA-IgG1 and ACPA-IgG4 are distinct. Given that IgG1 and IgG4 have different Fc-receptor and complement binding affinities, this phenomenon likely affects ACPA effector- and immune-regulatory functions in an IgG isotype-specific manner. These findings further highlight the importance of antibody characterization in relation to functional in vivo and in vitro studies.
    PLoS ONE 11/2014; 9(11):e113924. DOI:10.1371/journal.pone.0113924 · 3.53 Impact Factor
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    ABSTRACT: A large portion of common variant loci associated with genetic risk for schizophrenia reside within noncoding sequence of unknown function. Here, we demonstrate promoter and enhancer enrichment in schizophrenia variants associated with expression quantitative trait loci (eQTL). The enrichment is greater when functional annotations derived from the human brain are used relative to peripheral tissues. Regulatory trait concordance analysis ranked genes within schizophrenia genome-wide significant loci for a potential functional role, based on colocalization of a risk SNP, eQTL, and regulatory element sequence. We identified potential physical interactions of noncontiguous proximal and distal regulatory elements. This was verified in prefrontal cortex and -induced pluripotent stem cell–derived neurons for the L-type calciumchannel (CACNA1C) risk locus. Our findings point to a functional link between schizophrenia-associated noncoding SNPs and 3D genome architecture associated with chromosomal loopings and transcriptional regulation in the brain.
    Cell Reports 11/2014; 9:1-13. DOI:10.1016/j.celrep.2014.10.015 · 7.21 Impact Factor
  • Annals of the Rheumatic Diseases 09/2014; 73(12). DOI:10.1136/annrheumdis-2014-206369 · 9.27 Impact Factor
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    ABSTRACT: Translational medicine is becoming increasingly dependent upon data generated from health care, clinical research, and molecular investigations. This increasing rate of production and diversity in data has brought about several challenges, including the need to integrate fragmented databases, enable secondary use of patient clinical data from health care in clinical research, and to create information systems that clinicians and biomedical researchers can readily use. Our case study effectively integrates requirements from the clinical and biomedical researcher perspectives in a translational medicine setting. Our three principal achievements are (a) a design of a user-friendly web-based system for management and integration of clinical and molecular databases, while adhering to proper de-identification and security measures; (b) providing a real-world test of the system functionalities using clinical cohorts; and (c) system integration with a clinical decision support system to demonstrate system interoperability. We engaged two active clinical cohorts, 747 psoriasis patients and 2001 rheumatoid arthritis patients, to demonstrate efficient query possibilities across the data sources, enable cohort stratification, extract variation in antibody patterns, study biomarker predictors of treatment response in RA patients, and to explore metabolic profiles of psoriasis patients. Finally, we demonstrated system interoperability by enabling integration with an established clinical decision support system in health care. To assure the usefulness and usability of the system, we followed two approaches. First, we created a graphical user interface supporting all user interactions. Secondly we carried out a system performance evaluation study where we measured the average response time in seconds for active users, http errors, and kilobits per second received and sent. The maximum response time was found to be 0.12 seconds; no server or client errors of any kind were detected. In conclusion, the system can readily be used by clinicians and biomedical researchers in a translational medicine setting.
    PLoS ONE 09/2014; 9(9):e104382. DOI:10.1371/journal.pone.0104382 · 3.53 Impact Factor
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    ABSTRACT: IntroductionGenetic susceptibility to complex diseases has been intensively studied during the last decade, yet only signals with small effect have been found leaving open the possibility that subgroups within complex traits show stronger association signals. In rheumatoid arthritis (RA), autoantibody production serves as a helpful discriminator in genetic studies and today anti-citrullinated cyclic peptide (anti-CCP) antibody positivity is employed for diagnosis of disease. The HLA-DRB1 locus is known as the most important genetic contributor for the risk of RA, but is not sufficient to drive autoimmunity and additional genetic and environmental factors are involved. Hence, we addressed the association of previously discovered RA loci with disease-specific autoantibody responses in RA patients stratified by HLA-DRB1*04.Methods We investigated 2178 patients from three RA cohorts from Sweden and Spain for 41 genetic variants and four autoantibodies, including the generic anti-CCP as well as specific responses towards citrullinated peptides from vimentin, alpha-enolase and type II collagen.ResultsOur data demonstrated different genetic associations of autoantibody-positive disease subgroups in relation to the presence of DRB1*04. Two specific subgroups of autoantibody-positive RA were identified. The SNP in PTPN22 was associated with presence of anti-citrullinated enolase peptide antibodies in carriers of HLA-DRB1*04 (Cochran-Mantel-Haenszel test P¿=¿0.0001, P corrected <0.05), whereas SNPs in CDK6 and PADI4 were associated with anti-CCP status in DRB1*04 negative patients (Cochran-Mantel-Haenszel test P¿=¿0.0004, P corrected <0.05 for both markers). Additionally we see allelic correlation with autoantibody titers for PTPN22 SNP rs2476601 and anti-citrullinated enolase peptide antibodies in carriers of HLA-DRB1*04 (Mann Whitney test P¿=¿0.02) and between CDK6 SNP rs42041 and anti-CCP in non-carriers of HLA-DRB1*04 (Mann Whitney test P¿=¿0.02).Conclusion These data point to alternative pathways for disease development in clinically similar RA subgroups and suggest an approach for study of genetic complexity of disease with strong contribution of HLA.
    Arthritis Research & Therapy 08/2014; 16(5):414. DOI:10.1186/s13075-014-0414-3 · 4.12 Impact Factor
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    ABSTRACT: Rheumatoid arthritis (RA) is a prototype for a criterion-defined inflammatory disease, for which the aetiology and initial molecular pathogenesis has been elusive for a long time. We describe in this Review how studies on the interplay between specific immunity, alongside genetic and environmental predisposing factors, provide new tools to understand the molecular basis of distinct subsets of the disease. A particular emphasis is on the possibility that pathogenic immune reactions might be initiated at other sites than the joints, and that the lungs could harbour such sites. New data strengthen this concept, showing that local immunity towards citrullinated proteins and accompanying inflammation might be present in the lungs early during disease development. This progress makes RA an interesting case for the future development of therapies that might be directed against disease-inducing immunity even before inflammation and destruction of joints has begun.
    Nature Reviews Rheumatology 07/2014; 10(11). DOI:10.1038/nrrheum.2014.115 · 10.25 Impact Factor
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    ABSTRACT: Introduction A major subset of patients with rheumatoid arthritis (RA) is characterised by the presence of circulating autoantibodies directed to citrullinated proteins/peptides (ACPA). These autoantibodies, which are commonly detected using an ELISA assay based on synthetic cyclic citrullinated peptides (CCP), predict clinical onset and a destructive disease course. In the present study, we have utilised plasma and synovial fluids from patients with RA, for the affinity purification and characterisation of anti-CCP2 reactive antibodies, with an aim to generate molecular tools that can be utilized in vitro and in vivo for future investigations into the pathobiology of the ACPA response. Specifically, this study aims to demonstrate that the surrogate marker CCP2 can capture ACPA that bind to autoantigens expressed in vivo, in the major inflammatory lesions of RA, i.e. in the rheumatoid joint. Methods Plasma (n = 16) and synovial fluid (n = 26) samples were collected from RA patients with anti-CCP2 IgG levels above 300 AU/ml. Total IgG was isolated on Protein G columns, and subsequently applied to CCP2 affinity columns. Purified anti-CCP2 IgG was analysed for reactivity and specificity using the CCPlus® ELISA assay, in-house peptide-ELISAs, western blot and immunohisto-/immunocytochemistry. Results Approximately 2 % of the total IgG pool in both plasma and synovial fluid was CCP2-reactive. Purified anti-CCP2 reactive antibodies from different patients showed differences in binding to CCP2 and differences in binding to citrullinated peptides from α-enolase, −vimentin, −fibrinogen, and -collagen type II, illustrating different ACPA fine-specificity profiles. Furthermore, the purified ACPA bound not only in vitro citrullinated proteins but more importantly, in vivo-generated epitopes on synovial fluid cells and synovial tissues from RA patients. Conclusions We have isolated ACPA from plasma and synovial fluid, and demonstrated that the CCP2 peptides, frequently used in diagnostic ELISA assays, de facto act as surrogate antigens for at least four different, well-characterised, largely non cross-reactive, ACPA fine-specificities. Moreover, we have determined the concentration and proportion of CCP2-reactive IgG molecules in rheumatoid plasma and synovial fluid, and we have shown that the purified ACPA can be used to detect both in vitro- and in vivo-generated citrullinated epitopes by various techniques. We anticipate that these antibodies will provide us with new opportunities to investigate the potential pathogenic effects of human ACPAs.
    Arthritis research & therapy 07/2014; 16(4). DOI:10.1186/ar4683 · 4.12 Impact Factor
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    ABSTRACT: Objective: Rheumatoid arthritis is thought to be a T cell mediated disease, based on its strong association with HLA class II alleles, clinical responsiveness to T cell directed therapies and the presence of CD4 T cells in rheumatoid joints. The presence of ACPA in RA serum and the association of these antibodies with HLA-DR4 alleles implicates citrullinated specific autoreactive T cells in the development and progression of RA. The goal of this study was to determine the character and specificity of auto-reactive T cell responses in RA.Methods: We developed a panel of HLA-DRB1*04:01 tetramers, selecting citrullinated peptides from synovial antigens and verifying their immunogenicity in DRB1*04:01 transgenic mice. Seven tetramers were used to examine the ex vivo frequency and surface phenotype of cit-specific T cells in RA and healthy subjects with DRB1*04:01 haplotypes using a magnetic enrichment procedure.Results: Cit-specific T cells were detectable in peripheral blood samples from both healthy subjects and RA patients. In comparison to healthy subjects, RA patients had significantly higher frequencies of cit-specific T cells and a greater proportion of these cells displayed a Th1 memory phenotype. Among RA subjects the frequency of cit-specific T cells was highest within the first 5 years after diagnosis of RA and was decreased in patients taking biologic therapies irrespective of disease duration.Conclusion: These findings link the presence of ACPA in RA with Th1 cells specific to citrullinated epitopes and provide tools for disease-specific immunomonitoring of autoreactive T cells. © 2014 American College of Rheumatology.
    07/2014; 66(7). DOI:10.1002/art.38637
  • Annals of the Rheumatic Diseases 06/2014; 73(Suppl 2):136-136. DOI:10.1136/annrheumdis-2014-eular.1592 · 9.27 Impact Factor
  • Annals of the Rheumatic Diseases 06/2014; 73(Suppl 2):408-408. DOI:10.1136/annrheumdis-2014-eular.4450 · 9.27 Impact Factor

Publication Stats

29k Citations
4,278.91 Total Impact Points


  • 1994–2015
    • Karolinska University Hospital
      • Department of Rheumatology
      Tukholma, Stockholm, Sweden
  • 1987–2015
    • Karolinska Institutet
      • • Institute of Environmental Medicine - IMM
      • • Department of Medicine, Huddinge
      • • Department of Rheumatology
      • • Department of Neurology
      Solna, Stockholm, Sweden
    • Ludwig Institute for Cancer Research Sweden
      Uppsala, Uppsala, Sweden
  • 2003–2014
    • Harvard Medical School
      Boston, Massachusetts, United States
  • 2011
    • University of Amsterdam
      • Faculty of Medicine AMC
      Amsterdamo, North Holland, Netherlands
  • 1975–2011
    • Uppsala University
      • • Department of Medical Sciences
      • • Department of Immunology, Genetics and Pathology
      • • The Rudbeck Laboratory
      • • Department of Medical Biochemistry and Microbiology
      Uppsala, Uppsala, Sweden
  • 2009
    • Stockholm County Council
      Tukholma, Stockholm, Sweden
  • 2008
    • Johns Hopkins Medicine
      • Department of Psychiatry and Behavioral Sciences
      Baltimore, Maryland, United States
    • Vietnam National University, Hanoi
      Hà Nội, Ha Nội, Vietnam
  • 2007
    • University of California, Davis
      Davis, California, United States
    • National University Hospital of Iceland
      Reikiavik, Capital Region, Iceland
    • Hospital Universitario Marques de Valdecilla
      Santander, Cantabria, Spain
    • Harvard University
      Cambridge, Massachusetts, United States
  • 2006
    • Stockholm University
      Tukholma, Stockholm, Sweden
    • Maastricht Universitair Medisch Centrum
      Maestricht, Limburg, Netherlands
  • 1986–2006
    • Lund University
      Lund, Skåne, Sweden
  • 2005
    • University of Innsbruck
      Innsbruck, Tyrol, Austria
  • 1987–2004
    • Uppsala University Hospital
      • • Department of Rheumatology
      • • Department of Surgical Sciences
      • • Department of Dermatology
      • • Department of Internal Medicine
      Uppsala, Uppsala, Sweden
  • 1992
    • University of South Florida
      Tampa, Florida, United States
  • 1986–1988
    • University of Gothenburg
      Goeteborg, Västra Götaland, Sweden
  • 1985
    • Umeå University
      Umeå, Västerbotten, Sweden
  • 1981
    • University of Helsinki
      • Transplantation Laboratory
      Helsinki, Uusimaa, Finland