Karin Lundberg

• PhD
• Associate Professor at Karolinska Institutet

Anti‐cyclic citrullinated peptide2 (CCP2) antibody positivity in rheumatoid arthritis (RA) and in the predisease phase, together with the success of B‐cell depletion, support a crucial role for B cells in RA pathogenesis. Yet, knowledge of B cells in the transition from autoimmunity to RA is limited, and therefore we here investigated B‐cell change...

Objective The antibody response against Porphyromonas gingivalis (Pg) is elevated in rheumatoid arthritis (RA), especially in patients with anti-citrullinated protein antibodies (ACPA). Here, we investigated whether antibodies against the Pg virulence factor arginine gingipain (Rgp) are associated with the RA-risk phase and development of arthritis...

Introduction Periodontitis is associated with rheumatoid arthritis (RA). One hypothesis posits that this connection arises from the formation of autoantibodies against citrullinated proteins (ACPA) in inflamed gums, possibly triggered by Porphyromonas gingivalis. We previously demonstrated an increased antibody response to P. gingivalis arginine gi...

Evidence suggests that self-tolerance is breached in the lung prior to the clinical onset of rheumatoid arthritis (RA) in the joints. The human leukocyte antigen DR (HLA-DR) shared epitope (SE) represents the strongest genetic risk factor for sero-positive RA. However, to our knowledge, the HLA-DR immunopeptidome of the RA lung and its link to HLA-...

Objective Autoantibodies serve as essential clinical biomarkers and may indicate etiological mechanisms in rheumatic diseases. In light of the increasing knowledge concerning the diversity and biologic implications of anti–citrullinated peptide/protein antibodies (ACPAs), we have re‐evaluated the association between the ACPA response and the HLA‐DR...

Background: Immune cells from rheumatoid arthritis (RA) patients display a reduced in vitro response to Porphyromonas gingivalis (P. gingivalis), which may have functional immune consequences. The aim of this study was to characterize, by flow cytometry, the frequency/activity of monocytes and naturally occurring myeloid dendritic cells (mDCs) in p...

Objective Studies suggest rheumatoid arthritis (RA) patients could benefit from periodontal treatment. However, published data are inconsistent, and there is a need for better-controlled research. Our study aims to address these limitations. Methods In this exploratory randomised delayed-start study, 22 RA patients with moderate/severe periodontit...

Patients with rheumatoid arthritis (RA) have altered levels of exhaled nitric oxide (NO) compared with healthy controls. Here, we investigated whether the clinical features of and immunological factors in RA pathogenesis could be linked to the NO lung dynamics in early disease. A total of 44 patients with early RA and anti-citrullinated peptide ant...

Objectives: To assess the association between venous thromboembolic (VTE) events and autoantibodies, following patients from rheumatoid arthritis (RA) diagnosis, measuring occurrence, levels and collective load of different autoantibodies against post-translational protein-modifications, in particular recognizing citrullination (e.g. citrullinated...

Based on the epidemiological link between periodontitis and rheumatoid arthritis (RA), and the unique feature of the periodontal bacterium Porphyromonas gingivalis to citrullinate proteins, it has been suggested that production of anti-citrullinated protein antibodies (ACPA), which are present in a majority of RA patients, may be triggered in the g...

There is accumulating data suggesting that periodontitis is associated with increased risk of systemic and autoimmune diseases, including cardiovascular disease, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), and there is an unmet need to identify these individuals early. With the periodontal bacteria Porphyromonas gingivalis (Pg...

Periodontal disease (PD) can be an important precipitating factor in the production of citrullinated proteins. Its importance is emphasized, but it is not the only way to produce citrullinated proteins. The aim of the current study was to determine the periodontal conditions and the salivary citrullinated protein content in patients with rheumatoid...

Background Seropositive rheumatoid arthritis (RA) is characterized by the presence of rheumatoid factor (RF) and anti-citrullinated protein autoantibodies (ACPA) with different fine-specificities. Yet, other serum anti-modified protein autoantibodies (AMPA), e.g. anti-carbamylated (Carb), anti-acetylated (KAc), and anti-malondialdehyde acetaldehyde...

Background Epidemiologic studies have demonstrated a link between periodontitis (PD) and rheumatoid arthritis (RA), specifically RA characterized by anti-citrullinated protein antibodies (ACPA). The keystone pathogen driving PD, Porphyromonas gingivalis (Pg), is the only pathogen known to express peptidylarginine deiminase (PAD), a citrullinating e...

Seropositive rheumatoid arthritis (RA) is characterized by the presence of rheumatoid factor (RF) and anti-citrullinated protein autoantibodies (ACPA) with different fine-specificities. Yet, other serum anti-modified protein autoantibodies (AMPA), e.g. anti-carbamylated (Carb), -acetylated (KAc), and malondialdehyde acetaldehyde (MAA) modified prot...

Patients with chronic inflammatory diseases are often treated with immunosuppressants and therefore are of particular concern during the SARS-CoV-2 pandemic. Serological tests will improve our understanding of the infection and immunity in this population, unless they tests give false positive results. The aim of this study was to evaluate the spec...

Objective Previously, only the HLA–DRB1 alleles have been assessed in rheumatoid arthritis (RA). The aim of the present study was to identify the key major histocompatibility complex (MHC) susceptibility factors showing a significant association with anti–carbamylated protein antibody–positive (anti‐CarP+) RA. Methods Analyses were restricted to R...

Objectives Patients with chronic inflammatory diseases are often treated with immunosuppressants and therefore are of particular concern during the SARS-CoV-2 pandemic. Serological tests will improve our understanding of the infection and immunity in this population, unless the tests give false positive results. The aim of this study was to evaluat...

Objective Anti–citrullinated protein antibodies (ACPAs) are a hallmark of seropositive rheumatoid arthritis (RA). Yet, the precise disease‐relevant autoantigens that are targeted by ACPAs remains a matter of debate. This study utilized patient‐derived monoclonal ACPAs, rather than serum autoantibody analysis, to characterize the multireactivity to...

Background: Rheumatoid arthritis (RA) is classified as seropositive or seronegative, depending on the presence/absence of rheumatoid factor (RF), primarily IgM RF, and/or anti-citrullinated protein antibodies (ACPA), commonly detected using anti-cyclic citrullinated peptide (CCP) assays. Known risk factors associate with the more severe seropositi...

B cells are postulated to be central in seropositive rheumatoid arthritis (RA). Here, we use exploratory mass cytometry (n = 23) and next-generation sequencing (n = 19) to study B-cell repertoire shifts in RA patients. Expression of several B-cell markers were significantly different in ACPA+ RA compared to healthy controls, including an increase i...

Background: Porphyromonas gingivalis (P.g) is unique among pathogens due to its ability to generate citrullinated proteins in an inflammatory milieu, potentially mediating the loss of immune tolerance, the production of anticitrullinated protein antibodies (ACPAs), and subsequently the development of rheumatoid arthritis (RA). Based on this hypothe...

Rheumatoid arthritis (RA) is the most common immune-mediated arthritis. Anti-citrullinated peptide antibodies (ACPA) are highly specific to RA and assayed with the commercial CCP2 assay. Genetic drivers of RA within the MHC are different for CCP2-positive and -negative subsets of RA, particularly at HLA-DRB1. However, aspartic acid at amino acid po...

Background Seropositive rheumatoid arthritis (RA) is associated with autoreactivity to citrullinated proteins and rheumatoid factor activity. The adaptive immune system and B cells are postulated to be central in RA pathogenesis, yet possible B-cell dysregulations have not been extensively studied. Here, we use exploratory mass cytometry and next g...

Background Antibodies targeting citrullinated proteins (ACPA) are highly specific for rheumatoid arthritis (RA). However, the etiology and molecular basis for ACPA production is still unclear. Based on an epidemiological association between RA and periodontitis (PD), and the unique ability of the oral pathogen P.gingivalis (Pg) to express a PAD enz...

Background The continuing increase of anti-citrullinated protein autoantibodies (ACPA) titers together with epitope spreading close to onset of disease, suggests that antibody responses to different citrullinated antigens may be critical in rheumatoid arthritis (RA) pathogenesis. Interestingly, monoclonal antibodies demonstrate reactivity to multip...

Career situation of first and presenting author Student for a master or a PhD. Introduction The presence of anti-citrullinated protein antibodies (ACPAs) is a hallmark of rheumatoid arthritis (RA). ACPAs specifically recognize citrullinated epitopes, a result of a post-translational modification catalyzed by peptidyl arginine deiminases (PAD). Bas...

Objective Anti–citrullinated protein antibodies (ACPAs) are a hallmark of rheumatoid arthritis (RA). Aside from autoantibody production, the function of autoantigen‐specific B cells remains poorly understood in the context of this disease. This study set out to elucidate autoantigen‐specific B cell functions through the isolation and immortalizatio...

Background: A relationship between rheumatoid arthritis (RA) and periodontitis has been suggested from findings that individuals with RA are prone to have advanced periodontitis and vice versa. In search of possible common pathogenetic features of these two diseases, we investigated the presence of citrullinated proteins and expression of endogeno...

Introduction Anti-citrullinated protein antibodies (ACPA) – a hallmark of rheumatoid arthritis – antedate joint inflammation. Based on the epidemiological association between RA and periodontal disease (PD),¹ it has been suggested that break of tolerance to citrullinated proteins may occur in the gum mucosa. This hypothesis is primarily based on th...

Autoreactive B cells have a central role in the pathogenesis of rheumatoid arthritis (RA), and recent findings have proposed that anti-citrullinated protein autoantibodies (ACPA) may be directly pathogenic. Herein, we demonstrate the frequency of variable-region glycosylation in single-cell cloned mAbs. A total of 14 ACPA mAbs were evaluated for pr...

Autoreactive B cells have a central role in the pathogenesis of rheumatoid arthritis (RA), and recent findings have proposed that anti-citrullinated protein autoantibodies (ACPA) may be directly pathogenic. Herein, we demonstrate the frequency of variable-region glycosylation in single-cell cloned mAbs. A total of 14 ACPA mAbs were evaluated for pr...

Introduction The second generation anticycliccitrullinated peptide (anti-CCP2) assay detects the majority but not all anticitrullinated protein/peptide antibodies (ACPA). Anti-CCP2-positive rheumatoid arthritis (RA) is associated with HLA-DRB1* shared epitope (SE) alleles and smoking. Using a multiplex assay to detect multiple specific ACPA, we hav...

Background Infection by common viruses has long been discussed in the aetiology of a number of autoimmune diseases, including rheumatoid arthritis (RA). However, studies investigating this hypothesis in RA show conflicting results. These studies often lack well-matched control populations, and many do not include data on autoantibodies, genetic ris...

Background Rheumatoid arthritis (RA) is characterised by autoantibodies to citrullinated proteins (ACPA). Smoking and specific HLA alleles are well-established risk factors for ACPA+RA, and more recently Porphyromonas gingivalis, a major cause of periodontitis (PD), has been linked to ACPA+RA. Our ambition with this study is to clone ACPA-specific...

Abstract Background An infection-immune association of periodontal disease with rheumatoid arthritis has been suggested. This study aimed to investigate the effect of pre-existing periodontitis on the development and the immune/inflammatory response of pristane-induced arthritis. Methods We investigated the effect of periodontitis induced by ligatu...

Objective Human leucocyte antigen (HLA)-DRB1∗13 alleles are associated with protection from anticitrullinated protein antibody (ACPA)-positive rheumatoid arthritis (RA). It is, however, unknown at which phase of disease development (seroconversion, ACPA maturation, disease onset or outcome) these alleles are most important. We therefore examined th...

Background The periodontal pathogen Porphyromonas gingivalis is hypothesized to be important in rheumatoid arthritis (RA) aetiology by inducing production of anti-citrullinated protein antibodies (ACPA). We have shown that ACPA precede RA onset by years, and that anti-P. gingivalis antibody levels are elevated in RA patients. The aim of this study...

Background Citrullination by the periodontal pathogen Porphyromonas gingivalis has been hypothesized to play a role in RA aetiology, by contributing to the production of anti-citrullinated protein antibodies (ACPA). We have previously shown that the ACPA response precedes RA by several years, and we have recently demonstrated elevated anti-P. gingi...

Background Periodontitis and other dental conditions have been associated with the pathogenesis of rheumatoid arthritis (RA). In addition, these dental pathologies are also important comorbidities for RA. Objectives We wished to evaluate the periodontal involvement of rheumatoid arthritis (RA) patients, and we correlated with various laboratory bi...

Innate immune cells are complex systems that can be simultaneously activated in a variety of ways. Common methods currently used to estimate the response of innate immune cells to stimuli are usually biased towards a single mode of activation. The aim of this study was to assess the possibility of designing an assay based on unbiased proteome analy...

Introduction: The possible hypothesis of a link between periodontitis and rheumatoid arthritis (RA), specifically anti-citrullinated protein antibody (ACPA) positive RA, prompted us to investigate the prevalence of periodontitis in the Swedish Epidemiological Investigation of RA (EIRA), a well-characterised population-based RA case-control cohort....

Validation of the diagnosis of periodontitis obtained from DHR compared to dental records. DHR, Dental Health Registry; CI, confidence interval. (PDF)

EIRA participants, RA cases and controls, without periodontal diagnostic codes (no diagnosis) and participants not identified (missing) in DHR. Results are presented as numbers (%). EIRA, Epidemiological Investigation of Rheumatoid Arthritis; DHR, Dental Health Registry; RA, rheumatoid arthritis. (PDF)

Characteristics of the total EIRA study population and the subjects identified in DHR. Results are presented as numbers (%). EIRA, Epidemiological Investigation of Rheumatoid Arthritis; DHR, Dental Health Registry; RA, rheumatoid arthritis; ACPA, anti-citrullinated protein antibody. N/A, not applicable. (PDF)

Background In addition to anti-citrullinated protein antibodies (ACPAs), antibodies targeting carbamylated (i.e., homocitrullinated) proteins (anti-CarP antibodies) have been described in rheumatoid arthritis (RA). However, the extent to which anti-CarP antibodies are truly distinct from ACPA remains unclear, and few studies have focused on specifi...

Objectives In addition to anti-citrullinated protein antibodies (ACPAs), antibodies targeting carbamylated (i.e. homocitrullinated) proteins (anti-CarP antibodies) have been described in rheumatoid arthritis (RA). However, the extent to which anti-CarP antibodies are truly distinct from ACPA remains unclear, and few studies have focused on specific...

Objectives We investigated whether citrullinated tenascin-C (cTNC), an extracellular matrix protein expressed at high levels in the joints of patients with rheumatoid arthritis (RA), is a target for the autoantibodies in RA. Methods Citrullinated sites were mapped by mass spectrometry in the fibrinogen-like globe (FBG) domain of tenascin-C treated...

Receptor activator of nuclear factor kappa B ligand (RANKL) is a key regulator of bone metabolism. Anti-citrullinated protein antibodies (ACPA) have been suggested to cause bone destruction by osteoclast activation. We investigated the relationship between RANKL and ACPA in patients with early untreated rheumatoid arthritis (RA). Patients with newl...

Supplementary Table 1. Quantitative comparison of protein levels by mass spectrometry in supernatants of stimulated neutrophils (SN) and DNase I–treated NET fraction of stimulated neutrophils (+DNase‐I and/or D) after in vitro induced NETosis. Supplementary Table 2. Citrullinated proteins detected by mass spectrometry in supernatants of stimulated...

Objectives: Rheumatoid arthritis (RA)-specific anti-citrullinated protein/peptide antibodies (ACPAs) appear before disease onset and are associated with bone destruction. We aimed to dissect the role of ACPAs in osteoclast (OC) activation and to identify key cellular mediators in this process. Methods: Polyclonal ACPA were isolated from the syno...

Objective: To investigate the role of the periodontal pathogen Porphyromonas gingivalis in the etiology of rheumatoid arthritis (RA) by analyzing the antibody response to the P gingivalis virulence factor arginine gingipain type B (RgpB) in relation to anti-citrullinated protein antibodies (ACPAs), smoking, and HLA-DRB1 shared epitope (SE) alleles...

Objective: An interesting and so far unexplained feature of chronic pain in autoimmune disease is the frequent disconnect between pain and inflammation. This is illustrated well in rheumatoid arthritis (RA) where pain in joints (arthralgia) may precede joint inflammation and persist even after successful anti-inflammatory treatment. In the present...

In the majority of patients with rheumatoid arthritis (RA), antibodies specifically recognize citrullinated autoantigens that are generated by peptidylarginine deiminases (PAD). Neutrophils express high levels of PAD and accumulate in the synovial fluid (SF) of RA patients during disease flares. Here, we tested the hypothesis that neutrophil cell d...

Monocytes are blood-borne cells of the innate immune system. They can be differentiated and activated into pro-inflammatory macrophages that might be employed in tumor immune therapy. Monocyte exposure to lipopolysaccharide (LPS) is a standard method to induce a pro-inflammatory macrophage state, with the resultant population comprising both adhere...

We have previously identified endogenously citrullinated peptides derived from fibrinogen in rheumatoid arthritis (RA) synovial tissues. In this study, we have investigated the auto-antigenicity of four of those citrullinated peptides and explored their feasibility to target anti-citrullinated protein/peptide antibodies (ACPA). The autoantigenic po...

Background Anti citrullinated protein antibodies (ACPA) associate with bone destruction in RA Objectives We aimed to characterize the molecular mechanisms responsible for APCAs effect. Methods ACPA positive and negative IgGs were isolated from synovial fluid (SF, n=26) and peripheral blood (PB, n=38) samples of RA patients. CD14+ monocytes from PB...

Objective: Human leucocyte antigen (HLA)-DRB1*13 alleles are associated with protection from anticitrullinated protein antibody (ACPA)-positive rheumatoid arthritis (RA). It is, however, unknown at which phase of disease development (seroconversion, ACPA maturation, disease onset or outcome) these alleles are most important. We therefore examined...

Background and objectives Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune condition where HLA DRB1 shared epitope (SE) alleles and cigarette smoking constitute well-established risk factors. Still, current knowledge does not explain the whole risk for developing RA. An attractive hypothesis has been that RA is triggered by an infecti...

Introduction: Smoking is a well-established risk factor for rheumatoid arthritis (RA), and it has been proposed that smoking-induced citrullination renders autoantigens immunogenic. To investigate this mechanism, we examined human lung tissue from 40 subjects with defined smoking status, with or without chronic obstructive pulmonary disease (COPD)...

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...

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 detai...

There is accumulating evidence that periodontitis is linked to rheumatoid arthritis (RA) and that this may be due to the pathogen Porphyromonas gingivalis possessing a peptidyl arginine deiminase (PPAD). This apparently unique bacterial enzyme is capable of producing citrullinated bacterial or host proteins which could break tolerance leading to th...

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 destruct...

In rheumatoid arthritis (RA), several genetic risk factors and smoking are strongly associated with the presence of anticitrullinated protein antibodies (ACPA), while much less is known about risk factors for ACPA-negative RA. Antibodies against carbamylated proteins (anti-CarP) have been described in both ACPA-positive and ACPA-negative RA patient...

In rheumatoid arthritis (RA), the presence of antibodies to citrullinated proteins (ACPA) is strongly associated with certain genetic risk factors and smoking. The recently identified antibodies against carbamylated proteins (anti-CarP) are present in part of ACPA-positive, but also ACPA-negative RA patients. This raised the question whether the pr...

Porphyromonas gingivalis, a major cause of chronic periodontitis (PD), has been implicated also in the aetiology of rheumatoid arthritis (RA), specifically in anti-citrullinated protein/peptide antibody (ACPA) positive RA, based on its unique property among pathogens to express a citrullinating peptidylarginine deiminase enzyme. To investigate this...

Background We have previously demonstrated that smoking induces citrullination in the lungs of healthy smokers and we know that ACPA develops in RA patients many years before disease onset. Objectives In this study we aimed to investigate the hypothesis that lung changes in association with smoking and ACPA might be a primary rather than a secondar...

Background Autoimmunity in rheumatoid arthritis (RA) is characterized by autoantibodies to citrullinated proteins/peptides (ACPA)1. These antibodies, present in 60-70% of patients, antedate clinical onset and associate with an erosive disease course, suggesting a direct pathogenic involvement in disease initiation and progression2. Objectives With...

Rheumatoid arthritis (RA) represents a disease where we have recently acquired new knowledge on etiology and molecular pathogenesis, by combining data from studies on genetic end environmental determinants of disease with molecular and cellular immunology. This combined approach has provided insights into the heterogeneous nature of the clinical sy...

Background/Purpose Presence of anti CCP2 antibodies identifies a subgroup of RA patients that are more prone to develop bone erosions. We hypothesised that anti CCP2 IgG might have a direct effect on bone, and thus investigated the effect of anti CCP2 IgG isolated from synovial fluid (SF) of RA patients on osteoclastogenesis and bone destruction in...

Background Anti-citrullinated peptide/protein antibodies (ACPAs) are the key pathogenic autoantibodies in rheumatoid arthritis (RA). Because smoking is a risk factor for RA and ACPA often appear years before the onset of disease, it has been proposed that the lung may be a site for priming the ACPA response. Previous studies using immunohistochemis...

Introduction Autoantibodies directed against citrullinated proteins/peptides (ACPAs) are highly specific and predictive for the development of rheumatoid arthritis (RA). Different subgroups of RA patients, which have different prognoses and may require different treatments, are characterized by different autoantibody profiles. The objective of this...

Objectives To increase understanding of the aetiology and pathogenesis of rheumatoid arthritis (RA), genetic and environmental risk factors for RA subsets, defined by the presence or absence of different anticitrullinated protein/peptide antibodies (ACPAs) targeting citrullinated peptides from α-enolase, vimentin, fibrinogen and collagen type II, w...