Jerzy Swierkot

Wroclaw Medical University, Vrotslav, Lower Silesian Voivodeship, Poland

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Publications (30)35.85 Total impact

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    ABSTRACT: Among the complex network of inflammatory cells involved in the pathogenesis of rheumatoid arthritis (RA), Th17 cells have recently been identified as key cells in the promotion of autoimmune processes, and joint destruction. The IL-23/Th17 signalling pathway, consisting of IL-23/IL-23R, IL-17A and IL-17F encoding genes, represents a candidate way for RA development with possible involvement in disease susceptibility and effect on disease progression. The present study aimed to determine the association between the polymorphic variants of the IL-17A (rs2275913), IL-17F (rs763780) and IL-23R (rs11209026) genes and RA susceptibility, progression and response to therapy with TNF-α inhibitors. Eighty-nine patients and 125 healthy individuals were investigated. The IL-17A polymorphism was found to affect RA progression and response to anti-TNF treatment. Female patients carrying the IL-17A wild-type genotype more frequently presented with stage 4 (8/24 vs. 6/47; p = 0.058) and were characterized by more active disease (the highest DAS28 score >5.1) after 3 months of therapy with the TNF inhibitors (12/23 vs. 15/45; p = 0.040). The IL-17F polymorphism appeared to be associated with susceptibility to the disease. The presence of the IL-17F minor variant (OR 3.97; p < 0.001) and its homozygosity (OR 29.62; p < 0.001) was more frequent among patients than healthy individuals. These results suggest that the polymorphisms within the IL-17A and IL-17F genes play a significant role in RA.
    Archivum Immunologiae et Therapiae Experimentalis 11/2014; DOI:10.1007/s00005-014-0319-5 · 2.38 Impact Factor
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    ABSTRACT: Introduction Despite the fact that therapy with TNF-α inhibitors constitutes a breakthrough in rheumatoid arthritis management, no improvement is still achieved in approximately 30% of cases. The aim of the study was to evaluate whether single nucleotide polymorphisms (SNPs) within the TNF-α and TNF receptor encoding genes affect the efficacy of therapy with TNF-α inhibitors in patients with RA. Methods Five SNPs within the TNF-α and TNF receptor encoding genes (TNFA: G-308A, G-238A, C-857T; TNFR1A G36A; TNFR1B T676G) were determined in 280 RA patients who had been treated with TNF-α inhibitors for at least 6 months or they stop therapy because of adverse events. The association between the relative change in DAS28 and SNP genotypes was tested by linear regression. Results At week 24, low disease activity or remission was achieved by 45% of the patients. After 6 months remission of the disease or low disease activity were more frequently observed among patients homozygous for the TNFR1A 36A allele than among those who were GG homozygotes (52% vs. 34%, P = 0.04). At week 24 DAS28 was significantly lower in the subgroup of patients homozygous for the TNFA-857T variant compared to the C allele carriers (P = 0.045). The other polymorphisms were not found to be significantly associated with EULAR response at week 12 and 24 of the anti-TNF treatment. Conclusions Homozygosity for the TNFR1A 36A allele and the TNFA-875T variant could act as a genetic factor associated with better response to anti-TNF treatment.
    Joint Bone Spine 10/2014; DOI:10.1016/j.jbspin.2014.08.006 · 3.22 Impact Factor
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    ABSTRACT: Interleukin-2 (IL-2) has been suggested to control Treg/Th17 balance. Recently, we reported a relationship of rheumatoid arthritis (RA) activity/progression with irreversible systemic Treg and Th1 defects including serum IL-2 shortage. Herein, we explore the role of in vitro stimulation with rIL-2 in the observed immune alterations reversal. Patients with stable or progressive RA were assigned to methotrexate (MTX) group or to TNF-alpha inhibitors (iTNF) group, respectively. Flow cytometric analyses were performed before and after 6 months of treatment. Circulating Th1, Th17, and Treg cells were determined before and after 72-h culture with anti-CD3 + rIL-2. Before therapy, 72-h stimulation restored recently observed phenotypic Th cell alterations, except for the enriched Th17 subset normalized as late as after therapy in all patients. Under 6-month therapy, anti-CD3 stimulation changed the Th cell distribution only in progressive RA; despite Th1 enrichment, it revealed Treg population defects, which were completely reversed by exogenous IL-2 added to the stimulating culture. Our paper shows that in aggressive RA patients exhibiting serum IL-2 shortage despite iTNF therapy, exogenous rIL-2 is capable of promoting Treg differentiation affected by chronic activation, thus supporting its use in the combined strategy of biologic treatment of the progressive form of RA.
    Inflammation 08/2014; 38(2). DOI:10.1007/s10753-014-9987-x · 1.92 Impact Factor
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    ABSTRACT: The most recent studies confirm the link between rheumatoid arthritis (RA) and periodontal disease. RA patients have higher prevalence of chronic periodontitis and periodontal disease is often more severe in these patients. Both RA and PD show similar pathophysiological mechanisms and risk factors. Autoimmunity to citrullinated peptides is the primary element in the pathogenesis of RA, not found in other diseases. Porphyromonas gingivalis, the major periodontal pathogen associated with the etiology of chronic periodontitis, is the only bacterium currently known to produce the enzyme peptidylarginine deiminase (PAD) allowing protein citrullination. This bacterium likely fulfils a significant role in the pathogenesis of RA due to its capacity for citrullination of its own protein and host peptides, which may result in a loss of immune tolerance. A few epidemiological studies also indicate the potential link between spondyloarthropathies and periodontal disease.
    Postępy Higieny i Medycyny Doświadczalnej (Advances in Hygiene and Experimental Medicine) 01/2014; 68:1171-9. DOI:10.5604/17322693.1121846
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    ABSTRACT: Paraneoplastic syndromes, which are discussed in this paper, are a heterogeneous group of disorders associated with cancer, but not directly caused by the physical effects of the primary tumor or its metastases. May precede the appearance of the malignant process, occur simultaneously or disclose in the course of cancer. Paraneoplastic syndromes may be caused directly by toxins produced by tumor cells, occur in the course of hypersensitivity reactions, or be the result of release of intracellular antigens. Due to the often similar systemic symptoms it is very important to evaluate the association of rheumatic diseases and cancer. Most paraneoplastic rheumatologic syndroms are difficult distinguishable from idiopathic rheumatologic disorders. The most common paraneoplastic syndromes include rheumatoid arthritis (RA)-like syndrome arthritis, inflammatory myopathies, hypertrophic osteoarthropathy, vasculitis and Raynaud's phenomenon.
    Postępy Higieny i Medycyny Doświadczalnej (Advances in Hygiene and Experimental Medicine) 01/2014; 68:944-954. DOI:10.5604/17322693.1111924
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    ABSTRACT: Systemic immune defects might reflect severely dysregulated control of chronic inflammation related to disease progression. Th17/Treg cell imbalance has been demonstrated to be involved in rheumatoid arthritis (RA) pathogenesis. Despite controversial results, a growing anti-inflammatory role in this process has been recently attributed to Th1 responses. The aim of the study was to estimate the extent of Th1/Th17/Treg imbalance in peripheral blood (PB) of patients with short- and long-term RA in relation to cytokine milieu and its reversal after therapy with methotrexate and/or TNF inhibitors, respectively. Patients with different duration of RA (median 6 vs. 120 months) in the active phase of RA were enrolled in this study. We performed flow cytometric analysis of PB Th1, Th17, and Treg populations together with estimation of serum cytokine concentrations using cytometric bead array. Disease activity was calculated on the basis of clinical and biochemical indices of inflammation (DAS28, ESR, CRP). All parameters were measured and correlated with each other before and after 6 months therapy. Elevated levels of circulating Th17 cells and IL-6 were found in all active patients, of which Th17 cells were down-regulated by the treatment. Significantly reduced Th1 and functional CTLA-4+ Treg cell frequencies as well as Th1 cytokines observed only in progressive RA seemed to be irreversible. Although therapy induced clinical improvement in almost all patients, those with advanced RA remained with signs of inflammation. Our report demonstrates that both the extent of systemic immune abnormalities and their restoration are dependent on duration of the active RA.
    Rheumatology International 11/2013; 34(2). DOI:10.1007/s00296-013-2895-9 · 1.63 Impact Factor
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    ABSTRACT: The chronic nature of rheumatoid arthritis (RA) suggests immune dysfunction, including persistent systemic activation. Therefore, we evaluated the activatory and inhibitory potential as well as proliferative activity of peripheral blood (PB) CD4+ T cells from RA patients in different stages of the disease and after different therapeutic interventions. We found that CD4+ T cells from RA patients were activated in vivo concerning decreased CD28 expression and increase of CD40L, CD69, and CTLA-4 expression; however, the extent of stimulation was suboptimal when compared to healthy controls. Consequently, impaired proliferative activities of these cells were found in all patients irrespective of the active disease duration. Treatment with methotrexate (MTX) and/or inhibitors of TNF-alpha (iTNF) did not significantly influence systemic activation in RA patients, which corresponded with the maintenance of inflammation markers; however, partial restoration of CD28 and CTLA-4 expression as well as clinical improvement were observed. In patients with early disease (the MTX group), we noted higher capacity of CD4+ T cells for restoration of T cell function, whereas cells from the iTNF group with progressive disease remained with a proliferative defect after the treatment. In conclusion, our study demonstrates that the dysregulated expression of molecules interfering with CD4+ T cell signaling may result in functional impairment of the effector T cells and correlates with disease progression.
    Pathology & Oncology Research 09/2013; DOI:10.1007/s12253-013-9687-0 · 1.56 Impact Factor
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    ABSTRACT: Patients with systemic inflammatory rheumatic diseases (such as rheumatoid arthritis, lupus erythematosus, systemic sclerosis, idiopathic inflammatory myopathies, or Sjögren's syndrome) are at increased risk of cancer, including hematological malignancies (leukemias and lymphomas), as well as non-hematological cancers (e.g. lung, esophageal, prostate or ovarian cancer). This increased risk for cancer development in patients with rheumatic diseases is attributed to the immune (autoimmune) processes and the medical treatment. Due to the often similar symptoms and the occurrence of systemic paraneoplastic syndromes it is very important to evaluate the association between rheumatic diseases and cancer. This paper presents issues concerning the development of cancer in patients with rheumatic diseases and the risk of cancer associated with drugs used for the treatment of rheumatic diseases.
    Postępy Higieny i Medycyny Doświadczalnej (Advances in Hygiene and Experimental Medicine) 01/2013; 67:1254-60. DOI:10.5604/17322693.1079819
  • Jerzy Swierkot
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    ABSTRACT: Strong interest in biosimilars dates back several years. In the coming years the patent protection ends for subsequent biological drugs, including monoclonal antibodies. This paper organizes the most important facts related to the issue of biosimilars. A biosimilar is a biotherapeutic product which is similar in terms of quality, efficacy and safety to an already licensed reference biotherapeutic product'. It should be noted that biosimilars approved underthe current regulations of the European Medicines Agency (EMA) meet the stringent standards of safety, efficacy and immunogenicity. It is also important to realize that the biosimilar has the right to that name, if it is registered by regulatory authorities like EMA or FDA. One should not confuse biosimilar drugs with those which counterfeit or imitate. Clinical trials on the convertibility of innovative and biosimilar drugs are ongoing. Nevertheless,there is no regulatory framework and clear guidelines of conduct in this regard. In the near future, thanks to the registration of the first biosimilar monoclonal antibodies in rheumatology and gastroenterology the availability of biological treatment for patients should increase.
    Wiadomości lekarskie (Warsaw, Poland: 1960) 01/2013; 66(2 Pt 2):200-5.
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    ABSTRACT: Eosinophilic fasciitis characterized by symmetrical limbs' edema, myalgia, erythema, and progressive cutaneous and subcutaneous induration. Peripheral eosinophilia and hypergammaglobulinaemia are the most characteristic features of the disease. Histopathological examination shows fibrosis of fascia and deep layers of subcutaneous tissue with inflammatory infiltrates of eosinophiles, lymphocytes, histiocytes, and plasmocytes. The involvement of the organs occurs rarely in the course of the disease. The clinical case of eosinophilic fasciitis in a 78-year-old female patient was described.
    Wiadomości lekarskie (Warsaw, Poland: 1960) 01/2012; 65(2):138-41.
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    ABSTRACT: The paper contains basic information relating to treatment with immunoglobulin. Presented indications for their use, among others: primary immunodeficiency, Kawasaki disease, Guillain-Barre syndrome, chronic lymphocytic leukemia, primary thrombocytopenia. The factors to consider when choosing a preparation: the content of IgG, IgA, method of administration (intravenous or subcutaneous). The most frequent side effects, depending on the organ localization. Presented at risk (obesity, diabetes, renal failure, hypovolemia) in which these symptoms may occur especially frequently, which should be taken into account in the conduct of therapy (adequate hydration, low-dose, slow infusion).
    Polski merkuriusz lekarski: organ Polskiego Towarzystwa Lekarskiego 06/2011; 30(180):448-51.
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    ABSTRACT: Intravenous immunoglobulin (IVIG) preparations have been used as substitutional treatment in hypogammaglobulinemia for a long time. IVIG has now become an important treatment option in a number of clinical indications including autoimmune and acute inflammatory conditions. The mechanism of action is complex and not fully understood. The role of IVIG in many rheumatic diseases remain unclear and controversial because there are no randomized studies to support the use of IVIG. In 2006 the Department of Health in the UK started a process to review the use of immunoglobulin in various clinical indications and in 2008 the clinical guidelines for immunoglobulin use were published. Despite the introduction of newer biologic treatments IVIG could be a good treatment options in same patients with rheumatic diseases. Frequently they are used as second-line drugs after failure of therapy with corticosteroids and immunosuppressive drugs. As a first-line drugs in addition to Kawasaki disease the use of IVIG can be considered in the treatment of systemic connective tissue diseases when there are contraindications to the use of corticosteroids or immunosuppressive drugs, there are associated infections (including tuberculosis) and in pregnant women.
    Polski merkuriusz lekarski: organ Polskiego Towarzystwa Lekarskiego 06/2011; 30(180):435-40.
  • Jerzy Swierkot, Marta Madej
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    ABSTRACT: Aims of management of rheumatoid arthritis (RA) patients are not only a delay in progression of the disease and improvement of motor function, but also inhibition of progress of joint damage and achievement of remission. Early RA diagnosis is important, allowing introduction of active therapy as early as possible. Immediate treatment with disease modifying anti-rheumatic drugs (DMARDs) is necessary. In case DMARDs fail to evoke an adequate therapeutic response, introduction of biological drugs should be considered. Failure to achieve remission in case of many patients treated with classic DMARDs was a stimulus for intensive research on new drugs. Introduction of tumour necrosis factor alpha (TNF-alpha) inhibitors to therapy of RA 15 years ago caused a significant progress in management of the disease. Five TNF-alpha inhibitors are currently authorised (Infliximab, Etanercept, Adalimumab, Certolizumab and Golimumab) for RA treatment. Numerous clinical trials and observational programs proved higher efficacy of a combination therapy consisting of MTX and a TNF-alpha inhibitor in terms of RA remission. That applies mainly to patients burdened with risk factors of fast progression of the disease.
    Polski merkuriusz lekarski: organ Polskiego Towarzystwa Lekarskiego 04/2011; 30(178):283-8.
  • Jerzy Swierkot, Marta Madej
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    ABSTRACT: Current aims of management of rheumatoid arthritis (RA) patients are remission of the disease, or at least, achievement of its low activity. Early diagnosis of RA is highly important, allowing immediate start of therapy with classic disease modifying anti-rheumatic drugs (DMARDs). However, that kind of therapy does not guarantee achievement of therapeutic goals in all patients. In case of failure, introduction of biological drugs is necessary Despite a significant progress noted in RA therapy since introduction of tumour necrosis factor alpha (TNF-alpha) inhibitors several years ago, also that scheme failed to be effective in all cases of RA. New biological drugs characterised by a different mechanism of action than TNF-alpha inhibitors: Tocilizumab, Rituximab and Abatacept, are hope for non-responders to previous therapies.
    Polski merkuriusz lekarski: organ Polskiego Towarzystwa Lekarskiego 04/2011; 30(178):289-94.
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    ABSTRACT: Dysregulation in the immune system plays an important role in the pathogenesis of rheumatoid arthritis (RA). The persistent nature of arthritis strengthens the suggestion of immune dysfunction, consisting in predominance of the pro-inflammatory response. It seems that both local and systemic immune abnormalities, including PBMC secreting abnormal levels of pro- and anti-inflammatory cytokines, may be involved in the evolution of the disease. Helper T cells (Th) differentiate towards Th1, Th2, Th17, and Treg cells according to the cytokine microenvironment. Active RA results from the imbalance in distribution of functional pro-inflammatory Th17 and anti-inflammatory Treg cells. Affected Th1 cytokine secretion observed in the course of RA contributes to the increase in IL-17 production and Th17 infiltration in the synovial tissue. Current studies have demonstrated that pro-inflammatory Th1 cytokines may also exert an anti-inflammatory action on the balance between Th17 and Treg cells by promotion of Treg differentiation. In the paper, we also show the influence of TNF-alpha and its inhibitors on the distribution of Th subpopulations in RA patients.
    Postępy Higieny i Medycyny Doświadczalnej (Advances in Hygiene and Experimental Medicine) 01/2011; 65:397-403.
  • European Congress of Rheumatology; 06/2008
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    ABSTRACT: Common variable immunodeficiency (CVID) is the most frequent primary immunodeficiency syndrome in adults with equal sex prevalence. The syndrome typically presents as recurrent infections, with onset in childhood or young adulthood (between 20 and 30 years). CVID patients also have a higher prevalence of autoimmune diseases. A 38-year-old woman presented to the Rheumatology Department with polyarthralgia and fever of 39 degrees C of several months' duration. She had recurrent respiratory and gastrointestinal tract infections and pernicious anemia. Immunological studies showed decreased levels of IgG, IgM, complete IgA deficiency, increased percentage of CD8 lymphocytes, and a reduced CD4:CD8 ratio. HLA-DR typing was performed and we identified HLA-DRB1*01. Adequate intravenous immune globulin substitution as well as antibiotic and anti-inflammatory treatment resulted in the remission of arthritis. Hand radiograms repeated after 12 months showed narrowing of the intra-articular space in the right metacarpophalangeal and radiocarpal joints with multiple bone cysts and erosions. Erosions were found in both humeral heads as well. This prompted the diagnosis of rheumatoid arthritis. Arthritis can be a presenting symptom of primary immunodeficiency in adults, especially when accompanied by recurrent infections or autoimmune diseases. These patients require more advanced diagnostic procedures and therapeutic cooperation of different specialists.
    Clinical Rheumatology 03/2006; 25(1):92-4. DOI:10.1007/s10067-005-1141-6 · 1.77 Impact Factor
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    ABSTRACT: Diabetes mellitus affects the connective tissue in a variety of ways and so we observe a variety of alterations in the locomotor system including neuroarthropathy, hyperostosis, osteoporosis, cheiroarthropathy, limited joint mobility, muscular infarctions. The locomotor problems in diabetes may be considered articular, skeletal and soft-tissue lesions. Although some syndromes are observed exclusively in patients with diabetes, the majority of the rheumatic diseases found in patients with diabetes are also seen in the non-diabetes population, albeit at a much lower prevalence. Recent date show that more then 30% of patients with 1 or type 2 diabetes have some rheumatic manifestation. Some of the relations have known pathogenic mechanism, but most are based on epidemiologic findings. Some are the consequence of diabetic complications, others probably share pathogenic mechanisms with microvascular disease. There are also some disorders whose association with diabetes is not yet well established. The musculoskeletal complications of diabetes appear particularly when the disease is poorly controlled. Although the cardiovascular, renal and ocular complications of diabetes are the most severe, why shouldn't forgot about rheumatic syndromes.
    Polski merkuriusz lekarski: organ Polskiego Towarzystwa Lekarskiego 01/2006; 19(114):843-7.
  • Beata Nowak, Jerzy Swierkot, Jacek Szechiński
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    ABSTRACT: It may bring a lot of diagnostic difficulties to differenciate the systemic lupus erythematosus (SLE) and the infection with human immunodeficiency virus (HIV), since there are many multiorgan symptoms that are common for both of these diseases. Two case reports of patients with lupus-like syndrome, being the first manifestation of HIV infection, are described in this article. The aim of the article is to stress the importance of a very careful differentiating of SLE and HIV infection.
    Polskie archiwum medycyny wewnȩtrznej 12/2005; 114(5):1098-102. · 2.05 Impact Factor
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    ABSTRACT: We present a 31-year-old female patient with Behçet's disease. Behcet's disease is a systematic vasculitis of unknown cause involving veins and arteries of all sizes and having reccurent mucocutaneous and frequent ocular involvement. Our patient was suffering from oral and genital ulcers, fever, painful left knee and erythema nodosum. After having excluded differential diagnoses Behçet's disease was diagnosed. The treatment must be individual and it depends on the presence and severity of symptoms. The optimal improvement was observed after treatment with azathioprine, cyclosporine A and metylprednisolon. Behçet's disease is very seldom in our country but perhaps sometimes it isn't good diagnosed.
    Polskie archiwum medycyny wewnȩtrznej 07/2005; 113(6):580-4. · 2.05 Impact Factor

Publication Stats

96 Citations
35.85 Total Impact Points


  • 2004–2014
    • Wroclaw Medical University
      • • Department and Clinic of Rheumatology and Internal Medicine
      • • Department of Clinical Pharmacology
      Vrotslav, Lower Silesian Voivodeship, Poland
  • 2004–2013
    • Polish Academy of Sciences
      • Ludwik Hirszfeld Institute of Immunology and Experimental Therapy
      Warszawa, Masovian Voivodeship, Poland
  • 2011
    • Instytut Immunologii i Terapii Doświadczalnej im. Ludwika Hirszfelda
      Vrotslav, Lower Silesian Voivodeship, Poland