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Article ; Online: Ocular manifestations of rheumatic diseases.

Kemeny-Beke, Adam / Szodoray, Peter

2019 Volume 40, Issue 2, Page(s) 503–510

Abstract: Purpose: Our aim was to summarize key aspects of the pathomechanism and the ocular involvements of rheumatic and systemic autoimmune diseases.: Methods: Apart from a paper in French (Morax V, Ann Oculist 109:368-370, 1893), all papers referred to in ... ...

Abstract	Purpose: Our aim was to summarize key aspects of the pathomechanism and the ocular involvements of rheumatic and systemic autoimmune diseases. Methods: Apart from a paper in French (Morax V, Ann Oculist 109:368-370, 1893), all papers referred to in this article were published in English. All the materials were peer-reviewed full-text papers, letters, reviews, or book chapters obtained through a literature search of the PubMed database using the keywords ocular manifestations; pathogenesis; systemic inflammatory rheumatic diseases; rheumatoid arthritis; osteoarthritis; fibromyalgia; systemic lupus erythematosus; seronegative spondyloarthritis; ankylosing spondylitis; reactive arthritis; enteropathic arthritis; psoriatic arthritis; systemic sclerosis; polymyalgia rheumatica and covering all years available. Some statements articulated in this paper reflect the clinical experience of the authors in their tertiary-referral center. Results: Ophthalmic disorders are categorized by anatomical subgroups in all rheumatic diseases. The most common ocular manifestations are diverse types of inflammations of different tissues and dry eye disease (DED). Conclusion: The eye could be a responsive marker for the onset or aggravation of an immune reactivation in many rheumatic diseases, furthermore, ocular findings can antedate the diagnosis of the underlying rheumatic disease. By recognizing ocular manifestations of systemic rheumatic diseases it might be possible to avoid or at least delay many long term sequelae.
MeSH term(s)	Autoimmunity ; Dry Eye Syndromes/diagnosis ; Dry Eye Syndromes/etiology ; Humans ; Rheumatic Diseases/complications ; Rheumatic Diseases/immunology
Language	English
Publishing date	2019-10-03
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	800087-6
ISSN	1573-2630 ; 0165-5701
ISSN (online)	1573-2630
ISSN	0165-5701
DOI	10.1007/s10792-019-01183-9
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Article ; Online: Transcriptome analysis of primary adult B-cell lineage acute lymphoblastic leukemia identifies pathogenic variants and gene fusions, and predicts subtypes for in depth molecular diagnosis.

Podgorica, Mirjam / Drivet, Elsa / Viken, Jonas Krag / Richman, Alyssa / Vestbøstad, Johanne / Szodoray, Peter / Kvam, Ann Kristin / Wik, Hilde Skuterud / Tjønnfjord, Geir E / Munthe, Ludvig A / Frietze, Seth / Schjerven, Hilde

European journal of haematology

2024 Volume 112, Issue 5, Page(s) 731–742

Abstract: Background: B-cell acute lymphoblastic leukemia (B-ALL) is classified into subgroups based on known driver oncogenes and molecular lesions, including translocations and recurrent mutations. However, the current diagnostic tests do not identify subtypes ... ...

Abstract	Background: B-cell acute lymphoblastic leukemia (B-ALL) is classified into subgroups based on known driver oncogenes and molecular lesions, including translocations and recurrent mutations. However, the current diagnostic tests do not identify subtypes or oncogenic lesions for all B-ALL samples, creating a heterogeneous B-ALL group of unknown subtypes. Methods: We sorted primary adult B-ALL cells and performed transcriptome analysis by bulk RNA sequencing (RNA-seq). Results: Transcriptomic analysis of an adult B-ALL cohort allowed the classification of four patient samples with subtypes that were not previously revealed by standard gene panels. The leukemia of two patients were of the DUX4 subtype and two were CRLF2 Conclusion: We demonstrate that RNA-seq is an effective tool for precision medicine in B-ALL by providing comprehensive molecular profiling of leukemia cells, identifying subtype and oncogenic lesions, and stratifying patients for appropriate therapy.
MeSH term(s)	Adult ; Humans ; Cell Lineage ; Proto-Oncogene Proteins p21(ras)/genetics ; Transcriptome ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics ; Gene Expression Profiling ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/diagnosis ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/genetics ; Gene Fusion
Chemical Substances	Proto-Oncogene Proteins p21(ras) (EC 3.6.5.2)
Language	English
Publishing date	2024-01-08
Publishing country	England
Document type	Journal Article
ZDB-ID	392482-8
ISSN	1600-0609 ; 0902-4441
ISSN (online)	1600-0609
ISSN	0902-4441
DOI	10.1111/ejh.14164
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Article ; Online: Hematopoietic stem cell transplantation in autoimmune disorders: From immune-regulatory processes to clinical implications.

Zeher, Margit / Papp, Gábor / Nakken, Britt / Szodoray, Peter

Autoimmunity reviews

2017 Volume 16, Issue 8, Page(s) 817–825

Abstract: Autoimmune diseases are characterized by the development of autoreactive T- and B-cells targeting self-antigens, which eventually can result in chronic and persistent organ damage. The autologous hematopoietic stem cell transplantation (AHSCT) opened new ...

Abstract	Autoimmune diseases are characterized by the development of autoreactive T- and B-cells targeting self-antigens, which eventually can result in chronic and persistent organ damage. The autologous hematopoietic stem cell transplantation (AHSCT) opened new avenues in the treatment of patients with severe, treatment-resistant autoimmune diseases. This paper reviews the immune-regulatory mechanisms behind AHSCT, and also summarizes the experiences of clinical practice related to the therapy in organ-specific and systemic autoimmune diseases. It seems that the intricate interplay of various immune competent cells with regulatory capacity control in a synergistic manner the repopulated immune system after AHSCT, which potentially leads to a significant clinical improvement in certain autoimmune diseases. However, the widespread use of AHSCT was intrinsically limited, due to the serious side-effects of conditioning treatment and relatively high treatment-related mortality; moreover, the development of new effective and safe therapeutic approaches and the dawn of biological agents further limited its indications in the last decade. Nevertheless, with an appropriate patient selection and increased experience of transplant centres, the risks can be minimized, and AHSCT remained still a reasonable choice in multiple sclerosis and systemic sclerosis when the conventional therapy failed and further progression of disease is inevitable.
Language	English
Publishing date	2017-08
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	2144145-5
ISSN	1873-0183 ; 1568-9972
ISSN (online)	1873-0183
ISSN	1568-9972
DOI	10.1016/j.autrev.2017.05.020
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Article ; Online: Dyslipidemia in systemic lupus erythematosus.

Szabó, Melinda Zsuzsanna / Szodoray, Peter / Kiss, Emese

Immunologic research

2017 Volume 65, Issue 2, Page(s) 543–550

Abstract: Cardiovascular disease is one of the major causes of morbidity and mortality in patients with systemic lupus erythematosus (SLE). Accelerated atherosclerosis is related to traditional (age, hypertension, diabetes mellitus, dyslipidemia, obesity, smoking, ...

Abstract	Cardiovascular disease is one of the major causes of morbidity and mortality in patients with systemic lupus erythematosus (SLE). Accelerated atherosclerosis is related to traditional (age, hypertension, diabetes mellitus, dyslipidemia, obesity, smoking, and positive family history) and non-traditional, disease-related factors. Traditional risk factors are still more prominent in patients with lupus, as both hypertension and hypercholesterinemia were independently associated with premature atherosclerosis in several SLE cohorts. In this work, the authors summarize the epidemiology of dyslipidemia in lupus patients and review the latest results in the pathogenesis of lipid abnormalities. The prevalence of dyslipidemia, with elevations in total cholesterol (TC), low-density lipoprotein (LDL), triglyceride (TG), and apolipoprotein B (ApoB), and a reduction in low-density lipoprotein (LDL) levels are about 30% at the diagnosis of SLE rising to 60% after 3 years. Multiple pathogenetic mechanism is included, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) can suppress HDL and increase TG, auto-antibodies can cause the injury of the endothelium, lipoprotein lipase (LPL) activity can be reduced by circulating inflammatory mediators and antibodies, and increased oxidative stress may trigger a wide range of pro-atherogenic lipid modifications. As a major risk factor, dyslipidemia should be treated aggressively to minimize the risk of atherosclerosis and cardiovascular events. Randomized controlled trials with statins are controversial in the detention of atherosclerosis progression, but can be favorable by inhibiting immune activation that is the arterial wall and by decreasing lupus activity.
Language	English
Publishing date	2017-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	632857-x
ISSN	1559-0755 ; 0257-277X
ISSN (online)	1559-0755
ISSN	0257-277X
DOI	10.1007/s12026-016-8892-9
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Article ; Online: The Imbalance of Circulating Follicular T Helper Cell Subsets in Primary Sjögren's Syndrome Associates With Serological Alterations and Abnormal B-Cell Distribution.

Szabó, Krisztina / Jámbor, Ilona / Szántó, Antónia / Horváth, Ildikó Fanny / Tarr, Tünde / Nakken, Britt / Szodoray, Peter / Papp, Gábor

Frontiers in immunology

2021 Volume 12, Page(s) 639975

Abstract: Since B-cell hyperactivity and pathologic antibody response are key features in the immunopathogenesis of primary Sjögren's syndrome (pSS), the role of follicular T helper ( ... ...

Abstract	Since B-cell hyperactivity and pathologic antibody response are key features in the immunopathogenesis of primary Sjögren's syndrome (pSS), the role of follicular T helper (T
MeSH term(s)	Adult ; Aged ; Autoantibodies/immunology ; B-Lymphocytes/immunology ; CD40 Antigens/immunology ; Cell Differentiation/immunology ; Female ; Flow Cytometry/methods ; Humans ; Interleukins/immunology ; Male ; Middle Aged ; Sjogren's Syndrome/immunology ; T-Lymphocytes, Helper-Inducer/immunology ; T-Lymphocytes, Regulatory/immunology
Chemical Substances	Autoantibodies ; CD40 Antigens ; Interleukins ; interleukin-21 (MKM3CA6LT1)
Language	English
Publishing date	2021-03-19
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2021.639975
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Article ; Online: Toll-Like Receptor Pathways in Autoimmune Diseases.

Chen, Ji-Qing / Szodoray, Peter / Zeher, Margit

Clinical reviews in allergy & immunology

2016 Volume 50, Issue 1, Page(s) 1–17

Abstract: Autoimmune diseases are a family of chronic systemic inflammatory disorders, characterized by the dysregulation of the immune system which finally results in the break of tolerance to self-antigen. Several studies suggest that Toll-like receptors (TLRs) ... ...

Abstract	Autoimmune diseases are a family of chronic systemic inflammatory disorders, characterized by the dysregulation of the immune system which finally results in the break of tolerance to self-antigen. Several studies suggest that Toll-like receptors (TLRs) play an essential role in the pathogenesis of autoimmune diseases. TLRs belong to the family of pattern recognition receptors (PRRs) that recognize a wide range of pathogen-associated molecular patterns (PAMPs). TLRs are type I transmembrane proteins and located on various cellular membranes. Two main groups have been classified based on their location; the extracelluar group referred to the ones located on the plasma membrane while the intracellular group all located in endosomal compartments responsible for the recognition of nucleic acids. They are released by the host cells and trigger various intracellular pathways which results in the production of proinflammatory cytokines, chemokines, as well as the expression of co-stimulatory molecules to protect against invading microorganisms. In particular, TLR pathway-associated proteins, such as IRAK, TRAF, and SOCS, are often dysregulated in this group of diseases. TLR-associated gene expression profile analysis together with single nucleotide polymorphism (SNP) assessment could be important to explain the pathomechanism driving autoimmune diseases. In this review, we summarize recent findings on TLR pathway regulation in various autoimmune diseases, including Sjögren's syndrome (SS), systemic lupus erythematosus (SLE), multiple sclerosis (MS), rheumatoid arthritis (RA), systemic sclerosis (SSc), and psoriasis.
MeSH term(s)	Animals ; Autoimmune Diseases/diagnosis ; Autoimmune Diseases/etiology ; Autoimmune Diseases/metabolism ; Carrier Proteins/genetics ; Carrier Proteins/metabolism ; Genetic Predisposition to Disease ; Humans ; Multigene Family ; Polymorphism, Single Nucleotide ; Protein Binding ; Signal Transduction ; Toll-Like Receptors/chemistry ; Toll-Like Receptors/genetics ; Toll-Like Receptors/metabolism
Chemical Substances	Carrier Proteins ; Toll-Like Receptors
Language	English
Publishing date	2016-02
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1239045-8
ISSN	1559-0267 ; 1080-0549
ISSN (online)	1559-0267
ISSN	1080-0549
DOI	10.1007/s12016-015-8473-z
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Article ; Online: Regulatory immune cells and functions in autoimmunity and transplantation immunology.

Papp, Gabor / Boros, Peter / Nakken, Britt / Szodoray, Peter / Zeher, Margit

Autoimmunity reviews

2017 Volume 16, Issue 5, Page(s) 435–444

Abstract: In physiological circumstances, various tolerogenic mechanisms support the protection of self-structures during immune responses. However, quantitative and/or qualitative changes in regulatory immune cells and mediators can evoke auto-reactive immune ... ...

Abstract	In physiological circumstances, various tolerogenic mechanisms support the protection of self-structures during immune responses. However, quantitative and/or qualitative changes in regulatory immune cells and mediators can evoke auto-reactive immune responses, and upon susceptible genetic background, along with the presence of other concomitant etiological factors, autoimmune disease may develop. In transplant immunology, tolerogenic mechanisms are also critical, since the balance between of alloantigen-reactive effector cells and the regulatory immune cells will ultimately determine whether a graft is accepted or rejected. Better understanding of the immunological tolerance and the potential modulations of immune regulatory processes are crucial for developing effective therapies in autoimmune diseases as well as in organ transplantation. In this review, we focus on the novel insights regarding the impaired immune regulation and other relevant factors contributing to the development of auto-reactive and graft-reactive immune responses in autoimmune diseases and transplant rejection, respectively. We also address some promising approaches for modification of immune-regulatory processes and tolerogenic mechanisms in autoimmunity and solid organ transplantation, which may be beneficial in future therapeutic strategies.
MeSH term(s)	Autoimmunity/immunology ; Humans ; Immune Tolerance/immunology ; Immunologic Factors ; Transplantation Immunology/immunology
Chemical Substances	Immunologic Factors
Language	English
Publishing date	2017-05
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	2144145-5
ISSN	1873-0183 ; 1568-9972
ISSN (online)	1873-0183
ISSN	1568-9972
DOI	10.1016/j.autrev.2017.03.011
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Article: The Effect of Aerobic Exercise and Low-Impact Pilates Workout on the Adaptive Immune System.

Balogh, László / Szabó, Krisztina / Pucsok, József Márton / Jámbor, Ilona / Gyetvai, Ágnes / Mile, Marianna / Barna, Lilla / Szodoray, Peter / Tarr, Tünde / Csiki, Zoltán / Papp, Gábor

Journal of clinical medicine

2022 Volume 11, Issue 22

Abstract: Growing evidence indicates the pronounced effects of physical activity on immune functions, which may largely depend on the type of exercise, intensity, and duration. However, limited information is available regarding the effects of low-impact exercises, ...

Abstract	Growing evidence indicates the pronounced effects of physical activity on immune functions, which may largely depend on the type of exercise, intensity, and duration. However, limited information is available regarding the effects of low-impact exercises, especially on the level of adaptive immune system. Our study aimed to investigate and compare the changes in a broad spectrum of lymphocyte subtypes after 14 weeks of aerobic-type total-body-shaping workouts (TBSW) and Pilates workouts (PW) among healthy individuals. We determined the percentages of peripheral natural killer cells and different T and B lymphocyte subtypes with flow cytometry. At the end of the exercise program, significant changes in naïve and memory lymphocyte ratios were observed in TBSW group. Percentages of naïve cytotoxic T (Tc) cells elevated, frequencies of memory Tc and T-helper cell subsets decreased, and distribution of naïve and memory B cells rearranged. Proportions of activated T cells also showed significant changes. Nonetheless, percentages of anti-inflammatory interleukin (IL)-10-producing regulatory type 1 cells and immunosuppressive CD4
Language	English
Publishing date	2022-11-17
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm11226814
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Article ; Online: T-helper cell regulation of CD45 phosphatase activity by galectin-1 and CD43 governs chronic lymphocytic leukaemia proliferation.

Imbery, John F / Heinzelbecker, Julia / Jebsen, Jenny K / McGowan, Marc / Myklebust, Camilla / Bottini, Nunzio / Stanford, Stephanie M / Skånland, Sigrid S / Tveita, Anders / Tjønnfjord, Geir E / Munthe, Ludvig A / Szodoray, Peter / Nakken, Britt

British journal of haematology

2022 Volume 198, Issue 3, Page(s) 556–573

Abstract: Chronic lymphocytic leukaemia (CLL) is characterised by malignant mature-like B cells. Supportive to CLL cell survival is chronic B-cell receptor (BCR) signalling; however, emerging evidence demonstrates CLL cells proliferate in response to T-helper (Th) ...

Abstract	Chronic lymphocytic leukaemia (CLL) is characterised by malignant mature-like B cells. Supportive to CLL cell survival is chronic B-cell receptor (BCR) signalling; however, emerging evidence demonstrates CLL cells proliferate in response to T-helper (Th) cells in a CD40L-dependent manner. We showed provision of Th stimulation via CD40L upregulated CD45 phosphatase activity and BCR signalling in non-malignant B cells. Consequently, we hypothesised Th cell upregulation of CLL cell CD45 activity may be an important regulator of CLL BCR signalling and proliferation. Using patient-derived CLL cells in a culture system with activated autologous Th cells, results revealed increases in both Th and CLL cell CD45 activity, which correlated with enhanced downstream antigen receptor signalling and proliferation. Concomitantly increased was the surface expression of Galectin-1, a CD45 ligand, and CD43, a CLL immunophenotypic marker. Galectin-1/CD43 double expression defined a proliferative CLL cell population with enhanced CD45 activity. Targeting either Galectin-1 or CD43 using silencing, pharmacology, or monoclonal antibody strategies dampened CD45 activity and CLL cell proliferation. These results highlight a mechanism where activated Th cells drive CLL cell BCR signalling and proliferation via Galectin-1 and CD43-mediated regulation of CD45 activity, identifying modulation of CD45 phosphatase activity as a potential therapeutic target in CLL.
MeSH term(s)	CD40 Ligand ; Cell Proliferation ; Galectin 1 ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/pathology ; T-Lymphocytes, Helper-Inducer
Chemical Substances	Galectin 1 ; CD40 Ligand (147205-72-9)
Language	English
Publishing date	2022-06-02
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80077-6
ISSN	1365-2141 ; 0007-1048
ISSN (online)	1365-2141
ISSN	0007-1048
DOI	10.1111/bjh.18285
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Article ; Online: Protein array diagnostics for guiding therapy in rheumatoid arthritis.

Szodoray, Peter / Alex, Philip

Molecular diagnosis & therapy

2011 Volume 15, Issue 5, Page(s) 247–254

Abstract: Early diagnosis and effective management of rheumatoid arthritis (RA) are pivotal, given the progressive, chronic, inflammatory, multi-systemic nature of the disease. Currently, proper initiation of adequate, individually tailored interventions in RA is ... ...

Abstract	Early diagnosis and effective management of rheumatoid arthritis (RA) are pivotal, given the progressive, chronic, inflammatory, multi-systemic nature of the disease. Currently, proper initiation of adequate, individually tailored interventions in RA is delayed by the difficulty of early diagnosis and the limitations of disease activity and therapeutic response assessment tools. This is a significant challenge to rheumatologists, further complicated by the dynamic and progressively evolving autoimmune nature of RA, which is characterized by several immune mediators in a complex network that regulates the perpetuation of inflammation. Protein arrays constitute the most advanced current technology that can provide a comprehensive parallel analysis of this diverse network in RA, providing an individualized insight into immune status and host immune response. The last few years have seen significant transitions in the field of protein arrays, demonstrated by a technologic shift from the bench to the bedside, paving the way for the medical and scientific community to deliver patient-specific assessments and personalized management. Screening of protein arrays with sera or tissues from patients with RA enables the probing of immune responses and the identification of autoantibody signatures that can be used for the diagnosis and therapeutic management of patients. This article reviews the technology and the applications for protein arrays in the diagnosis and prognosis of RA. Clinical assessment tools could be derived from protein arrays, which may provide a means to continually track patients, allowing better evaluation of intervention strategies on a patient-specific basis and identification of diagnostic and disease activity biomarkers that could be used to guide optimal therapy in RA.
MeSH term(s)	Animals ; Arthritis, Rheumatoid/diagnosis ; Arthritis, Rheumatoid/metabolism ; Humans ; Protein Array Analysis/methods
Language	English
Publishing date	2011-11-17
Publishing country	New Zealand
Document type	Journal Article ; Review
ZDB-ID	2232796-4
ISSN	1179-2000 ; 1177-1062
ISSN (online)	1179-2000
ISSN	1177-1062
DOI	10.2165/11595290-000000000-00000
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