22 results on '"Rönnelid, Johan"'
Search Results
2. The citrullinated/native index of autoantibodies against hnRNP-DL predicts an individual “window of treatment success” in RA patients
- Author
-
Marklein, Bianka, Jenning, Madeleine, Konthur, Zoltán, Häupl, Thomas, Welzel, Franziska, Nonhoff, Ute, Krobitsch, Sylvia, Mulder, Debbie M., Koenders, Marije I., Joshua, Vijay, Cope, Andrew P., Shlomchik, Mark J., Anders, Hans-Joachim, Burmester, Gerd R., Hensvold, Aase, Catrina, Anca I., Rönnelid, Johan, Steiner, Günter, and Skriner, Karl
- Published
- 2021
- Full Text
- View/download PDF
3. Increased levels of anti-dsDNA antibodies in immune complexes before treatment with belimumab associate with clinical response in patients with systemic lupus erythematosus
- Author
-
Sohrabian, Azita, Parodis, Ioannis, Carlströmer-Berthén, Nellie, Frodlund, Martina, Jönsen, Andreas, Zickert, Agneta, Sjöwall, Christopher, Bengtsson, Anders A., Gunnarsson, Iva, and Rönnelid, Johan
- Published
- 2019
- Full Text
- View/download PDF
4. Two subgroups in systemic lupus erythematosus with features of antiphospholipid or Sjögren’s syndrome differ in molecular signatures and treatment perspectives
- Author
-
Idborg, Helena, Zandian, Arash, Sandberg, Ann-Sofi, Nilsson, Bo, Elvin, Kerstin, Truedsson, Lennart, Sohrabian, Azita, Rönnelid, Johan, Mo, John, Grosso, Giorgia, Kvarnström, Marika, Gunnarsson, Iva, Lehtiö, Janne, Nilsson, Peter, Svenungsson, Elisabet, and Jakobsson, Per-Johan
- Published
- 2019
- Full Text
- View/download PDF
5. Immune Complex-Mediated Cytokine Production is Regulated by Classical Complement Activation both In Vivo and In Vitro
- Author
-
Rönnelid, Johan, Åhlin, Erik, Nilsson, Bo, Nilsson-Ekdahl, Kristina, Mathsson, Linda, and Lambris, John D., editor
- Published
- 2008
- Full Text
- View/download PDF
6. Anti-phosphatidylserine/prothrombin antibodies and thrombosis associate positively with HLA-DRB1*13 and negatively with HLA-DRB1*03 in SLE.
- Author
-
Elbagir, Sahwa, Diaz-Gallo, Lina-Marcela, Grosso, Giorgia, Zickert, Agneta, Gunnarsson, Iva, Mahler, Michael, Svenungsson, Elisabet, and Rönnelid, Johan
- Subjects
THROMBOSIS risk factors ,THROMBOSIS prevention ,AUTOANTIBODIES ,THROMBOSIS ,CARDIOVASCULAR diseases risk factors ,STATISTICS ,TRIGLYCERIDES ,HLA-B27 antigen ,ANTIPHOSPHOLIPID syndrome ,MULTIVARIATE analysis ,PROTHROMBIN ,ALLELES ,RISK assessment ,COMPARATIVE studies ,RESEARCH funding ,DESCRIPTIVE statistics ,PHOSPHOLIPIDS ,SYSTEMIC lupus erythematosus ,ODDS ratio ,HIGH density lipoproteins ,LIPIDS ,DISEASE risk factors - Abstract
Objectives Emerging evidence demonstrates that aPS-PT associate with thrombotic events. Genetic predisposition, including HLA-DRB1 alleles, is known to contribute to the occurrence of conventional aPL [anti-β
2 glycoprotein-I (anti-β2 GPI) and aCL]. We investigated associations between aPS-PT and HLA-DRB1 * alleles and thrombosis in SLE. Conventional aPL were included for comparison. Methods We included 341 consecutive SLE patients, with information on general cardiovascular risk factors, including blood lipids, LA and thrombotic events. aPS/PT, anti-β2 GPI and aCL of IgA/G/M isotypes and LA were quantified. Results aPS/PT antibodies associated positively with HLA-DRB1 *13 [odds ratio (OR) 2.7, P = 0.002], whereas anti-β2 GPI and aCL antibodies associated primarily with HLA-DRB1*04 (OR 2.5, P = 0.0005). These associations remained after adjustment for age, gender and other HLA-DRB1 * alleles. HLA-DRB1*13 , but not DRB1*04 , remained as an independent risk factor for thrombosis and APS after adjustment for aPL and cardiovascular risk factors. The association between DRB1*13 and thrombosis was mediated by aPS-PT positivity. HLA-DRB1*03 , on the other hand, associated negatively with thrombotic events as well as all aPL using both uni- and multivariate analyses. HLA-DRB1*03 had a thrombo-protective effect in aPL-positive patients. Additionally, HLA-DRB1*03 was associated with a favourable lipid profile regarding high-density lipoprotein and triglycerides. Conclusions HLA-DRB1*13 confers risk for both aPS-PT and thrombotic events in lupus. The association between HLA-DRB1*13 and thrombosis is largely, but not totally, mediated through aPS-PT. HLA-DRB1*03 was negatively associated with aPL and positively with favourable lipid levels. Thus, HLA-DRB1*03 seems to identify a subgroup of SLE patients with reduced vascular risk. [ABSTRACT FROM AUTHOR]- Published
- 2023
- Full Text
- View/download PDF
7. False Positive Results in SARS-CoV-2 Serological Tests for Samples From Patients With Chronic Inflammatory Diseases
- Author
-
Kharlamova, Nastya, Dunn, Nicky, Bedri, Sahl K., Jerling, Svante, Almgren, Malin, Faustini, Francesca, Gunnarsson, Iva, Rönnelid, Johan, Pullerits, Rille, Gjertsson, Inger, Lundberg, Karin, Månberg, Anna, Pin, Elisa, Nilsson, Peter, Hober, Sophia, Fink, Katharina, and Fogdell-Hahn, Anna
- Subjects
rheumatoid arthritis ,Reumatologi och inflammation ,systemic lupus erythematosus ,SARS-CoV-2 ,autoantibodies ,Immunologi inom det medicinska området ,autoimmunity ,diagnostics ,Immunology in the medical area ,skin and connective tissue diseases ,multiple sclerosis ,rheumatoid factor ,Rheumatology and Autoimmunity - Abstract
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 specificity of SARS-Cov-2 serological assays using samples from patients with chronic inflammatory diseases collected prior to April 2019, thus defined as negative. Samples from patients with multiple sclerosis (MS, n=10), rheumatoid arthritis (RA, n=47) with or without rheumatoid factor (RF) and/or anti-cyclic citrullinated peptide antibodies (anti-CCP2) and systemic lupus erythematosus (SLE, n=10) with or without RF, were analyzed for SARS-CoV-2 antibodies using 17 commercially available lateral flow assays (LFA), two ELISA kits and one in-house developed IgG multiplex bead-based assay. Six LFA and the in-house validated IgG assay correctly produced negative results for all samples. However, the majority of assays (n=13), gave false positive signal for samples from patients with RA and SLE. This was most notable in samples from RF positive RA patients. No false positive samples were detected in any assay using samples from patients with MS. Poor specificity of commercial serological assays could possibly be, at least partly, due to interfering antibodies in samples from patients with chronic inflammatory diseases. For these patients, the risk of false positivity should be considered when interpreting results of the SARS-CoV-2 serological assays.
- Published
- 2021
8. Autoantibody and Cytokine Profiles during Treatment with Belimumab in Patients with Systemic Lupus Erythematosus
- Author
-
Parodis, Ioannis, Åkerström, Emil, Sjöwall, Christopher, Sohrabian, Azita, Jönsen, Andreas, Gomez, Alvaro, Frodlund, Martina, Zickert, Agneta, Bengtsson, Anders A, Rönnelid, Johan, and Gunnarsson, Iva
- Subjects
Adult ,Male ,autoantibodies ,B cells ,autoimmunity ,biologic therapies ,cytokines ,immune complexes ,systemic lupus erythematosus ,Interferon alpha-2 ,Antibodies, Monoclonal, Humanized ,Severity of Illness Index ,Article ,lcsh:Chemistry ,Humans ,Lupus Erythematosus, Systemic ,lcsh:QH301-705.5 ,Rheumatology and Autoimmunity ,Reumatologi och inflammation ,Interleukin-6 ,Middle Aged ,Interleukin-10 ,Treatment Outcome ,lcsh:Biology (General) ,lcsh:QD1-999 ,Antibodies, Antinuclear ,Female - Abstract
We investigated whether belimumab treatment impacts on levels of autoantibodies and cytokines of interest in systemic lupus erythematosus (SLE). Longitudinally collected serum samples from 78 belimumab-treated Swedish SLE patients were analysed. Serum cytokine levels were determined using Luminex xMAP technology, and nuclear antigen autoantibody specificities using addressable laser bead immunoassay. In patients with detectable levels at baseline, interferon (IFN)-a2 levels were lower at month 6 (median; interquartile range (IQR): 8.9; 1.5-54.9 pg/mL) versus baseline (28.4; 20.9-100.3 pg/mL; p = 0.043). Interleukin (IL)-6 (baseline: 7.1; 2.9-16.1 pg/mL) decreased from month 6 (0.5; 0.5-6.3 pg/mL; p = 0.018) and throughout a 24 month follow-up. IL-10 (baseline: 12.6; 2.8-29.7 pg/mL) showed more rapid decreases from month 3 (1.8; 0.6-9.1 pg/mL; p = 0.003). Levels of anti-dsDNA (p < 0.001), anti-Smith antigen (Sm) (p = 0.002), anti-U1 small nuclear ribonucleoprotein (U1RNP) (p < 0.001), anti-Sm-U1RNP complex (p = 0.028), and anti-ribosomal P (p = 0.012) antibodies decreased from month 3 and remained decreased. Anti-Sm positivity at baseline was associated with higher probability and/or shorter time to achieve sustained SLE responder index-4 response (hazard ratio (HR): 2.52; 95% CI: 1.20-5.29; p = 0.015), independently of other factors. Decline of IL-6 levels through month 3 was greater in responders. In summary, belimumab treatment lowered IFN-a2, IL-6, and IL-10 levels, as well as levels of multiple autoantibodies, however after different time spans. Notably, anti-Sm positivity and early decline in IL-6 levels were associated with favorable treatment outcome. Funding agencies: The Swedish Research Council; Swedish RheumatismAssociation (R-859621; R-862161; R-844801); Professor Nanna Svartz Foundation (2018-00250); Ulla and Roland Gustafsson Foundation (2019-12); King Gustaf V’s 80-year Foundation; Swedish Society of Medicine; Ingegerd Johansson Donation; King Gustaf V and Queen Victoria’s Foundation of Freemasons; Region Östergötland (ALF grants); Region Stockholm; Region Uppsala; Region Skåne; Faculty of Medicine, Lund University; AlfredÖsterlund’s Foundation; Anna-Greta Crafoord Foundation; Greta and Johan Kock’s Foundation; Skåne UniversityHospital; and the Karolinska Institutet Foundations.
- Published
- 2020
9. Associations with thrombosis are stronger for antiphosphatidylserine/prothrombin antibodies than for the Sydney criteria antiphospholipid antibody tests in SLE.
- Author
-
Elbagir, Sahwa, Grosso, Giorgia, Mohammed, NasrEldeen A, Elshafie, Amir I, Elagib, Elnour M, Zickert, Agneta, Manivel, Vivek Anand, Pertsinidou, Eleftheria, Nur, Musa A. M, Gunnarsson, Iva, Rönnelid, Johan, and Svenungsson, Elisabet
- Subjects
PHOSPHOLIPID antibodies ,PROTHROMBIN ,ANTIBODY titer ,THROMBOSIS ,IMMUNOGLOBULINS - Abstract
Objectives: Antiphosphatidylserine/prothrombin complex antibodies (aPS/PT) are risk factors for thrombosis, yet further validation of their clinical relevance in different ethnic groups is required. We investigated the performance of aPS/PT of IgA/G/M isotypes among Sudanese and Swedish systemic lupus erythematosus (SLE) patients. Methods: Consecutive SLE patients/matched controls from Sudan (n = 91/102) and Sweden (n = 332/163) were included. All patients fulfilled the 1982 ACR SLE classification criteria. IgA/G/M of aPS/PT, anti-cardiolipin and anti-β
2 glycoprotein I (anti-β2 GPI) were tested in both cohorts, and lupus anticoagulant (LA) also in the Swedish cohort. Clinical antiphospholipid syndrome-related events and atherosclerosis, measured as carotid plaques were assessed for associations. Univariate and multivariate analyses adjusting for cardiovascular risk factors were performed. Results: Sudanese SLE patients had higher levels of IgM aPS/PT, but using national cut-offs, the frequency of positivity was similar to Swedish patients for all isotypes. Among Swedish patients, all isotypes of aPS/PT associated with venous thromboembolism (VTE), while only IgA aPS/PT associated with arterial thrombosis (AT). aPS/PT antibodies associated strongly with LA and they were, independently, the best predictor for VTE. Double positivity for aPS/PT and anti-β2 GPI associated with higher VTE risk than the conventional triple positivity. Carotid plaques did not associate with any antiphospholipid antibody. Conclusions: IgA aPS/PT associated with AT, and the association of IgG/M aPS/PT with VTE outperforms LA and criteria antiphospholipid antibodies in Swedish SLE patients. Furthermore, double positivity for aPS/PT and anti-β2 GPI performed better than conventional triple positivity. Future studies need to address if aPS/PT can replace LA, as this would simplify clinical procedures. [ABSTRACT FROM AUTHOR]- Published
- 2021
- Full Text
- View/download PDF
10. High IgA antiphospholipid autoantibodies in healthy Sudanese explain the increased prevalence among Sudanese compared to Swedish systemic lupus erythematosus patients.
- Author
-
Elbagir, Sahwa, Elshafie, Amir I, Elagib, Elnour M, Mohammed, NasrEldeen A, Aledrissy, Mawahib IE, Manivel, Vivek Anand, Pertsinidou, Eleftheria, Nur, Musa AM, Gunnarsson, Iva, Svenungsson, Elisabet, and Rönnelid, Johan
- Subjects
SYSTEMIC lupus erythematosus ,AUTOANTIBODIES ,PHOSPHOLIPID antibodies ,MEDICAL records - Abstract
Objectives: IgA antiphospholipid antibodies (aPL) are prevalent in systemic lupus erythematosus (SLE) patients of African American, Afro-Caribbean and South African origin. Nevertheless, data from North Africa are lacking, and most studies use manufacturer-suggested cut-offs based on Caucasian controls. Therefore, we compared aPL isotypes in Sudanese and Swedish SLE patients using nation-based cut-offs. Methods: Consecutive SLE patients and age- and sex-matched controls from Sudan (N = 115/106) and Sweden (N = 340/318) were included. All patients fulfilled the 1982 American College of Rheumatology SLE classification criteria. Antiphospholipid syndrome–related events were obtained from patients' records. IgA/G/M anticardiolipin and anti-β
2 glycoprotein I (β2 GPI) were analysed with two independent assays. IgA anti-β2 GPI domain 1 (D1) was also investigated. Manufacturers' cut-offs and the 95th and 99th percentile cut-offs based on national controls were used. Results: Sudanese patients and controls had higher levels and were more often positive for IgA aPL than Swedes when using manufacturers' cut-offs. In contrast, using national cut-offs, the increase in IgA aPL among Sudanese patients was lost. Occurrence of IgA anti-D1 did not differ between the countries. Venous thromboses were less common among Sudanese patients and did not associate with aPL. No clinical associations were observed with IgA anti-β2 GPI in Sudanese patients. Thromboses in Swedes were associated with IgG/M aPL. Fetal loss was associated with aPL in both cohorts. Conclusions: IgA anti-β2 GPI prevalence was higher among Sudanese compared to Swedish patients when manufacturers' cut-offs were used. This situation was reversed when applying national cut-offs. Anti-D1 was not increased in Sudanese patients. Previous studies on populations of African origin, which demonstrate a high prevalence of IgA aPL positivity, should be re-evaluated using a similar cut-off approach. [ABSTRACT FROM AUTHOR]- Published
- 2020
- Full Text
- View/download PDF
11. Sjögren Syndrome in Systemic Lupus Erythematosus: A Subset Characterized by a Systemic Inflammatory State.
- Author
-
Ruacho, Guillermo, Kvarnström, Marika, Zickert, Agneta, Oke, Vilija, Rönnelid, Johan, Eketjäll, Susanna, Elvin, Kerstin, Gunnarsson, Iva, and Svenungsson, Elisabet
- Subjects
SYSTEMIC lupus erythematosus ,AUTOIMMUNE diseases ,ANKYLOSING spondylitis ,CLINICAL trials ,RHEUMATOLOGY - Abstract
Objective: An often-neglected subset of patients with systemic lupus erythematosus (SLE) is those with secondary Sjögren syndrome (SLE-sSS). Further, primary SS overlaps and can be difficult to delineate from SLE. To shed light on the SLE-sSS subset, we investigated a large and well-characterized SLE cohort, comparing patients with SLE-sSS and SLE patients without SS (SLE-nonsSS) and controls.Methods: We included 504 consecutive patients with SLE, fulfilling the 1982 revised American College of Rheumatology criteria, and 319 controls from the general population, matched for age and sex to the first 319 patients. SLE-sSS was defined according to the American-European Consensus Criteria (AECC). A thorough clinical examination, including subjective and objective quantifications of sicca symptoms, was performed in all participants. Autoantibodies and 20 selected cytokines were measured by luminex and multiplex analysis, respectively.Results: SLE-sSS, as defined by AECC, occurred in 23% of the patients with SLE. In comparison to SLE-nonsSS, the SLE-sSS group was older and more frequently female. Leukopenia and peripheral neuropathy were more frequent and nephritis less frequent. Circulating levels of 6/20 investigated proinflammatory cytokines [tumor necrosis factor-α, interleukin (IL) 6, monocyte chemoattractant protein 4, macrophage inflammatory protein 1β, IL-12/IL-23p40, and interferon γ-induced protein 10], total IgG, anti-SSA/Ro52, anti-SSA/Ro60, anti-SSB/La antibodies, and rheumatoid factor (IgM and IgA) were higher in the SLE-sSS group (p < 0.05 for all comparisons).Conclusion: The frequency of SLE-sSS increased with age and affected roughly one-quarter of all patients with SLE. Despite less internal organ involvement, a systemic inflammatory state with high levels of proinflammatory cytokines is present in the SLE-sSS subgroup. This is a novel observation that may affect future understanding and treatment of the SLE-sSS subset. [ABSTRACT FROM AUTHOR]- Published
- 2020
- Full Text
- View/download PDF
12. Sudanese and Swedish patients with systemic lupus erythematosus: immunological and clinical comparisons.
- Author
-
Elbagir, Sahwa, Elshafie, Amir I, Elagib, Elnour M, Mohammed, NasrEldeen A, Aledrissy, Mawahib I E, Sohrabian, Azita, Nur, Musa A M, Svenungsson, Elisabet, Gunnarsson, Iva, and Rönnelid, Johan
- Subjects
AGE distribution ,AUTOANTIBODIES ,COMPARATIVE studies ,PERIPHERAL neuropathy ,HEALTH outcome assessment ,QUESTIONNAIRES ,SYSTEMIC lupus erythematosus ,DISEASE prevalence ,CASE-control method ,DISEASE duration ,DESCRIPTIVE statistics - Abstract
Objective SLE is known to have an aggressive phenotype in black populations, but data from African cohorts are largely lacking. We therefore compared immunological and clinical profiles between Sudanese and Swedish patients using similar tools. Methods Consecutive SLE patients from Sudan (n = 115) and Sweden (n = 340) and from 106 Sudanese and 318 Swedish age- and sex-matched controls were included. All patients fulfilled the 1982 ACR classification criteria for SLE. Ten ANA-associated specificities and C1q-binding immune complexes (CICs) were measured. Cut-offs were established based on Sudanese and Swedish controls, respectively. Disease activity was measured with a modified SLEDAI and organ damage with the SLICC Damage Index. In a nested case–control design, Swedish and Sudanese patients were matched for age and disease duration. Results Females constituted 95.6% and 88.1% of Sudanese and Swedish patients, respectively (P = 0.02), with younger age at inclusion (33 vs 47.7 years; P < 0.0001) and shorter disease duration (5 vs 14 years; P < 0.0001) among Sudanese patients. Anti-Sm antibodies were more frequent in Sudanese patients, whereas anti-dsDNA, anti-histone and CICs were higher in Swedish patients. In the matched analyses, there was a trend for higher SLEDAI among Swedes. However, Sudanese patients had more damage, solely attributed to high frequencies of cranial/peripheral neuropathy and diabetes. Conclusion While anti-Sm is more common in Sudan than in Sweden, the opposite is found for anti-dsDNA. Sudanese patients had higher damage scores, mainly because of neuropathy and diabetes. Sudanese patients were younger, with a shorter SLE duration, possibly indicating a more severe disease course with impact on survival rates. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
13. A WHO Reference Reagent for lupus (anti-dsDNA) antibodies: international collaborative study to evaluate a candidate preparation.
- Author
-
Fox, Bernard J., Hockley, Jason, Rigsby, Peter, Dolman, Carl, Meroni, Pier Luigi, and Rönnelid, Johan
- Abstract
Introduction: Antibodies against double-stranded DNA (anti-dsDNA) are a specific biomarker for systemic lupus erythematosus (SLE). The first WHO International Standard (IS) for anti-dsDNA (established in 1985), which was used to assign units to diagnostic tests, was exhausted over a decade ago.Methods: Plasma from a patient with SLE was first evaluated in 42 European laboratories. The plasma was thereafter used by the National Institute for Biological Standards and Control to prepare a candidate WHO reference preparation for lupus (anti-dsDNA) antibodies. That preparation, coded 15/174, was subjected to an international collaborative study, including 36 laboratories from 17 countries.Results: The plasma mainly contained anti-dsDNA, other anti-chromatin antibodies and anti-Ku. The international collaborative study showed that the field would benefit from 15/174 as a common reference reagent improving differences in performance between different assays. However, no statistically meaningful overall potency or assay parallelism and commutability could be shown.Conclusion: 15/174 cannot be considered equivalent to the first IS for anti-dsDNA (Wo/80) and was established as a WHO Reference Reagent for lupus (oligo-specific) anti-dsDNA antibodies with a nominal value of 100 units/ampoule. This preparation is intended to be used to align test methods quantifying levels of anti-dsDNA antibodies. [ABSTRACT FROM AUTHOR]- Published
- 2019
- Full Text
- View/download PDF
14. Identification of specific antinuclear antibodies in dogs using a line immunoassay and enzyme-linked immunosorbent assay
- Author
-
Bremer, Hanna D., Lattwein, Erik, Renneker, Stefanie, Lilliehöök, Inger, Rönnelid, Johan, and Hansson-Hamlin, Helene
- Subjects
musculoskeletal diseases ,Immunology ,Clinical Science ,veterinary(all) ,Systemic Lupus Erythematosus ,stomatognathic diseases ,Antinuclear antibodies ,Veterinärmedicin ,immune system diseases ,Immunologi ,Dog ,Veterinary Science ,skin and connective tissue diseases ,Diagnostics ,Rheumatology and Autoimmunity - Abstract
Circulating antinuclear antibodies (ANA) are commonly present in the systemic autoimmune disease Systemic Lupus Erythematosus (SLE) and in other systemic rheumatic diseases, in humans as well as in dogs. The indirect immunofluorescence (IIF)-ANA test is the standard method for detecting ANA. Further testing for specific ANA with immunoblot techniques or ELISAs is routinely performed in humans to aid in the diagnosis and monitoring of disease. Several specific ANA identified in humans have been identified also in suspected canine SLE but, in contrast to humans, investigation of autoantibodies in canine SLE is mainly restricted to the IIF-ANA test. Our aim was to identify both known and novel specific ANA in dogs and to investigate if different IIF-ANA patterns are associated with different specific ANA in dogs. Sera from 240 dogs with suspicion of autoimmune disease (210 IIF-ANA positive (ANA(pos)) and 30 IIF-ANA negative (ANA(neg))) as well as sera from 27 healthy controls were included. The samples were analysed with a line immunoassay, LIA (Euroline ANA Profile 5, Euroimmun, Lubeck, Germany) and four different ELISAs (Euroimmun). The ANA(pos) dogs were divided in two groups depending on the type of IIF-ANA pattern. Of the 210 ANA(pos) samples 68 were classified as ANA homogenous (ANA(H)) and 141 as ANA speckled (ANA(S)), one sample was not possible to classify. Dogs in the ANA(H) group had, compared to the other groups, most frequently high levels of anti-double stranded deoxyribonucleic acid (dsDNA) and anti-nucleosome ANA. Anti-dsDNA antibodies were confirmed in some dogs with the Crithidia luciliae indirect immunofluorescence test (CLIFT).The frequency of ANA(H) dogs with values above those observed in the healthy group was significantly higher compared to ANA(S) dogs for anti-dsDNA, anti-nucleosome, and anti-histone reactivity. Dogs in the ANA(S) group had, compared to the other groups, most frequently high levels of anti-ribonucleoproteins (RNP) and/or anti-Smith (Sm) antibodies. Reactivity against Sjogren's syndrome related antigens (SS)-A (including the Ro-60 and Ro-52 subcomponents), SS-B, histidyl tRNA synthetase (Jo-1), topoisomerase I antigen (Scl-70), polymyositis-scleroderma antigen (PM-Scl) and proliferating cell nuclear antigen (PCNA) was also noted in individual dogs. In conclusion, by using a commercial LIA and different ELISAs originally developed for detection of human ANA, we identified several specific ANA in serum samples from dogs sampled for IIF-ANA testing. Further, we found that the types of IIF-ANA pattern were associated with reactivity against some particular nuclear antigens. (C) 2015 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
- Published
- 2015
15. Circulating Levels of Interferon Regulatory Factor-5 Associates With Subgroups of Systemic Lupus Erythematosus Patients.
- Author
-
Idborg, Helena, Zandian, Arash, Ossipova, Elena, Wigren, Edvard, Preger, Charlotta, Mobarrez, Fariborz, Checa, Antonio, Sohrabian, Azita, Pucholt, Pascal, Sandling, Johanna K., Fernandes-Cerqueira, Cátia, Rönnelid, Johan, Oke, Vilija, Grosso, Giorgia, Kvarnström, Marika, Larsson, Anders, Wheelock, Craig E., Syvänen, Ann-Christine, Rönnblom, Lars, and Kultima, Kim
- Subjects
INTERFERON regulatory factors ,SYSTEMIC lupus erythematosus ,BIOLOGICAL tags ,IMMUNOGLOBULINS ,PROTEOMICS ,BLOOD proteins ,IMMUNOLOGY - Abstract
Systemic Lupus Erythematosus (SLE) is a heterogeneous autoimmune disease, which currently lacks specific diagnostic biomarkers. The diversity within the patients obstructs clinical trials but may also reflect differences in underlying pathogenesis. Our objective was to obtain protein profiles to identify potential general biomarkers of SLE and to determine molecular subgroups within SLE for patient stratification. Plasma samples from a cross-sectional study of well-characterized SLE patients (n = 379) and matched population controls (n = 316) were analyzed by antibody suspension bead array targeting 281 proteins. To investigate the differences between SLE and controls, Mann–Whitney U -test with Bonferroni correction, generalized linear modeling and receiver operating characteristics (ROC) analysis were performed. K-means clustering was used to identify molecular SLE subgroups. We identified Interferon regulating factor 5 (IRF5), solute carrier family 22 member 2 (SLC22A2) and S100 calcium binding protein A12 (S100A12) as the three proteins with the largest fold change between SLE patients and controls (SLE/Control = 1.4, 1.4, and 1.2 respectively). The lowest p -values comparing SLE patients and controls were obtained for S100A12, Matrix metalloproteinase-1 (MMP1) and SLC22A2 (p
adjusted = 3 × 10−9 , 3 × 10−6 , and 5 × 10−6 respectively). In a set of 15 potential biomarkers differentiating SLE patients and controls, two of the proteins were transcription factors, i.e., IRF5 and SAM pointed domain containing ETS transcription factor (SPDEF). IRF5 was up-regulated while SPDEF was found to be down-regulated in SLE patients. Unsupervised clustering of all investigated proteins identified three molecular subgroups among SLE patients, characterized by (1) high levels of rheumatoid factor-IgM, (2) low IRF5, and (3) high IRF5. IRF5 expressing microparticles were analyzed by flow cytometry in a subset of patients to confirm the presence of IRF5 in plasma and detection of extracellular IRF5 was further confirmed by immunoprecipitation-mass spectrometry (IP-MS). Interestingly IRF5, a known genetic risk factor for SLE, was detected extracellularly and suggested by unsupervised clustering analysis to differentiate between SLE subgroups. Our results imply a set of circulating molecules as markers of possible pathogenic importance in SLE. We believe that these findings could be of relevance for understanding the pathogenesis and diversity of SLE, as well as for selection of patients in clinical trials. [ABSTRACT FROM AUTHOR]- Published
- 2019
- Full Text
- View/download PDF
16. Regulation of the Interferon-α Production Induced by RNA-Containing Immune Complexes in Plasmacytoid Dendritic Cells.
- Author
-
Maija-Leena Eloranta, Lövgren, Tanja, Finke, Doreen, Mathsson, Linda, Rönnelid, Johan, Kastner, Berthold, Alm, Gunnar V., and Rönnblom, Lars
- Subjects
RNA ,INTERFERONS ,DENDRITIC cells ,SYSTEMIC lupus erythematosus ,MONOCYTES ,KILLER cells - Abstract
The article presents a study on regulating the interferon-α production caused by RNA-containing immune complexes in plasmacytoid dendritic cells (PDC). It mentions the use of purified normal PDCs from peripheral blood mononuclear cells (PBMCs) which were cocultivated with other cells separated from systemic lupus erythematosus (SLE) patients. Results show that IFNα produced by PDCs in PBMC cultures was inhibited by monocytes while natural killing (NK) cells were stimulatory.
- Published
- 2009
- Full Text
- View/download PDF
17. Comment on: Sudanese and Swedish patients with systemic lupus erythematosus, immunological and clinical comparisons: reply.
- Author
-
Elbagir, Sahwa, Gunnarsson, Iva, and Rönnelid, Johan
- Subjects
AUTOANTIBODIES ,PERIPHERAL neuropathy ,SYSTEMIC lupus erythematosus ,DISEASE duration - Published
- 2020
- Full Text
- View/download PDF
18. Cryoglobulin-induced cytokine production via Fc γRIIa: inverse effects of complement blockade on the production of TNF- α and IL-10. Implications for the growth of malignant B-cell clones.
- Author
-
Mathsson, Linda, Tejde, Andreas, Carlson, Kristina, Höglund, Martin, Nilsson, Bo, Nilsson-Ekdahl, Kristina, and Rönnelid, Johan
- Subjects
CRYOGLOBULINS ,AUTOANTIBODIES ,CYTOKINES ,TUMOR necrosis factors ,LYMPHOPROLIFERATIVE disorders ,SYSTEMIC lupus erythematosus - Abstract
Monoclonal antibodies produced by patients with lymphoproliferative diseases sometimes appear as cryoglobulins (CG), immunoglobulins (Ig) that reversibly agglutinate and form immune complexes (IC) when cooled below normal body temperature or through variation in pH and ionic strength. In accordance with our findings of IC-induced cytokine production from peripheral blood mononuclear cells (PBMC) in systemic lupus erythematosus, we investigated whether CG can also induce cytokine production. One IgG and one IgM type I CG from two patients with multiple myeloma and Waldenstrom's macroglobulinaemia were individually purified and added to PBMC cultures. In separate experiments temperature and ionic strength were varied, or Fc γRIIa, Fc γRIII and complement activation were blocked; supernatant cytokine levels were then determined by enzyme-linked immunosorbent assay. CG-induced cytokine production from monocytes varied with precipitation induced by changes in temperature and ionic strength and was mediated via Fc γRIIa- and complement-dependent mechanisms. Complement blockade resulted in increased IgG CG-induced interleukin (IL)-10 production that was inversely correlated with decreased production of tumour necrosis factor- α. CG-induced IL-10 might be a growth factor for malignant B-lymphocytes in CG-associated lymphoproliferative diseases with constant complement consumption. Knowledge of mechanisms underlying CG-induced cytokine production can be useful for designing treatments for type I CG-associated pathology in lymphoproliferative diseases. [ABSTRACT FROM AUTHOR]
- Published
- 2005
- Full Text
- View/download PDF
19. Accumulation of antinuclear associated antibodies in circulating immune complexes is more prominent in SLE patients from Sudan than Sweden.
- Author
-
Elbagir, Sahwa, Sohrabian, Azita, Elshafie, Amir I., Elagib, Elnour M., Mohammed, Nasr Eldeen A., Nur, Musa A. M., Svenungsson, Elisabet, Gunnarsson, Iva, and Rönnelid, Johan
- Subjects
ANTINUCLEAR factors ,SYSTEMIC lupus erythematosus ,IMMUNE complexes - Abstract
The role of anti-nuclear autoantibody (ANA) specificities in immune complexes (IC) formation has been studied to a limited extent in SLE, and not at all in African SLE patients. We compared ANA in IC from Sudanese and Swedish SLE patients. We included 93 Sudanese and 332 Swedish SLE patients fulfilling the 1982 ACR criteria. IC were captured using C1q-coated beads. ANA specificities were quantified in sera and IC. Results were related to modified SLEDAI. Whereas serum levels of anti-Sm, anti-dsDNA and anti-ribosomal P were higher in Swedish patients, IC levels of most ANA specificities were higher among Sudanese patients. This difference was especially prominent for anti-chromatin antibodies, which remained after adjustment for age, disease duration and treatment. Total levels of C1q-binding IC correlated with levels of specific ANA in IC, with highest correlations for anti-chromatin antibodies among Sudanese patients. Whereas occurrence of anti- SSA/Ro60, anti-histone and anti-U1RNP in both serum and IC associated with high SLEDAI score, anti-dsDNA in IC but not in serum associated with high SLEDAI. ANA, especially antibodies targeting chromatin, accumulate more in IC from Sudanese SLE patients. If the autoantibody fraction forming IC is pathogenically important, this might explain the generally described severe SLE in black populations. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
20. Depressed serum IgM levels in SLE are restricted to defined subgroups.
- Author
-
Grönwall, Caroline, Hardt, Uta, Gustafsson, Johanna T., Kvarnström, Marika, Grosso, Giorgia, Padykov, Leonid, Gunnarsson, Iva, Svenungsson, Elisabet, Elvin, Kerstin, Jensen-Urstad, Kerstin, Rönnelid, Johan, and Silverman, Gregg J.
- Subjects
- *
ANTIPHOSPHOLIPID syndrome , *AUTOANTIBODIES , *SYSTEMIC lupus erythematosus , *IMMUNOGLOBULIN G , *IMMUNOGLOBULIN M , *SJOGREN'S syndrome - Abstract
Natural IgM autoantibodies have been proposed to convey protection from autoimmune pathogenesis. Herein, we investigated the IgM responses in 396 systemic lupus erythematosus (SLE) patients, divided into subgroups based on distinct autoantibody profiles. Depressed IgM levels were more common in SLE than in matched population controls. Strikingly, an autoreactivity profile defined by IgG anti-Ro/La was associated with reduced levels of specific natural IgM targeting phosphorylcholine (PC) antigens and malondialdehyde (MDA) modified-protein, as well as total IgM, while no differences were detected in SLE patients with an autoreactivity profile defined by anti-cardiolipin/β 2 glycoprotein-I. We also observed an association of reduced IgM levels with the HLA-DRB1*03 allelic variant among SLE patients and controls. Associations of low IgM anti-PC with cardiovascular disease were primarily found in patients without antiphospholipid antibodies. These studies further highlight the clinical relevance of depressed IgM. Our results suggest that low IgM levels in SLE patients reflect immunological and genetic differences between SLE subgroups. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
21. Smoking and pre-existing organ damage reduce the efficacy of belimumab in systemic lupus erythematosus.
- Author
-
Parodis, Ioannis, Sjöwall, Christopher, Jönsen, Andreas, Ramsköld, Daniel, Zickert, Agneta, Frodlund, Martina, Sohrabian, Azita, Arnaud, Laurent, Rönnelid, Johan, Malmström, Vivianne, Bengtsson, Anders A., and Gunnarsson, Iva
- Subjects
- *
LUPUS erythematosus , *SMOKING , *BELIMUMAB , *BIOLOGICALS , *TREATMENT effectiveness - Abstract
Objectives Belimumab is the first biologic drug approved for Systemic Lupus Erythematosus (SLE). Here, we aimed to investigate the effects of belimumab on clinical and serologic outcomes, and sought to identify predictors of treatment response in three Swedish real-life settings. Methods Fifty-eight patients were enrolled at initiation of belimumab and followed longitudinally for up to 53 months. Surveillance outcomes included the SLE Disease Activity Index 2000 (SLEDAI-2K), 100 mm Visual Analogue Scales for Physician's Global Assessment (PGA), fatigue, pain and general health, and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). Assessment of treatment response included the SLE responder index (SRI). B lymphocyte stimulator (BLyS) levels were determined using ELISA. Results SLEDAI-2K (median baseline score: 8.0; IQR: 4.0–13.8), PGA and corticosteroid use decreased during therapy, and patients reported improvements on fatigue, pain, and general health ( p < 0.0001 for all). SDI scores remained stable ( p = 0.08). Patients with baseline SDI scores > 1 showed decreased probability and prolonged time to attain SRI response (HR: 0.449; 95% CI: 0.208–0.967), as did current smokers compared with non-smokers (HR: 0.103; 95% CI: 0.025–0.427). In contrast, baseline BLyS levels ≥ 1.2 ng/mL predicted increased probability and shorter time to attain SRI response (HR: 2.566; 95% CI: 1.222–5.387). Conclusions Disease activity and corticosteroid usage decreased, patient-reported outcomes improved, and no significant organ damage was accrued during follow-up. Smoking and organ damage predicted reduced treatment efficacy. These findings might contribute to a better selection of patients who are likely to benefit from belimumab. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
22. Are IF-ANA the guiding light for SLE classification in the real-world setting?
- Author
-
Gualtierotti, Roberta, Meroni, Pier Luigi, Beltagy, Asmaa, El-Girby, Amira, Emmi, Giacomo, Chizzolini, Carlo, Migliorini, Paola, Bossuyt, Xavier, Pregnolato, Francesca, Rönnelid, Johan, Borghi, Maria Orietta, and Moroni, Gabriella
- Subjects
- *
SYSTEMIC lupus erythematosus , *CLASSIFICATION - Published
- 2022
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.