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Article ; Online: Capillary leak syndrome was associated with more severe multisystem inflammatory syndrome in children during the COVID-19 pandemic.

Kahn, Robin / Mossberg, Maria / Berthold, Elisabet / Schmidt, Tobias / Najibi, Seyed Morteza / Månsson, Bengt / Król, Petra

Acta paediatrica (Oslo, Norway : 1992)

2024

Abstract: Aim: This population-based study investigated the occurrence of capillary leak syndrome (CLS) in children with multisystem inflammatory syndrome in children (MIS-C), associated with COVID-19. We also examined associations between CLS and MIS-C disease ... ...

Abstract	Aim: This population-based study investigated the occurrence of capillary leak syndrome (CLS) in children with multisystem inflammatory syndrome in children (MIS-C), associated with COVID-19. We also examined associations between CLS and MIS-C disease severity. Methods: All eligible individuals aged 0-18 years, who were diagnosed with MIS-C in Skåne, southern Sweden, from 1 April 2020 to 31 July 2021, were studied. They were all included in the Pediatric Rheumatology Quality Register and clinical and laboratory data were compared between patients with and without CLS. Results: We included 31 patients (61% male) with MIS-C in the study. The median age at diagnosis was 10.6 years (range 1.99-17.15) and 45% developed CLS. All six patients who required intensive care had CLS. Patients with CLS also had a higher incidence of reduced cardiac function, measured as low ejection fraction. The CLS group exhibited significantly higher C-reactive protein values (p < 0.001) and N-terminal pro-B-type natriuretic peptide levels (p < 0.001), as well as lower platelet counts (p = 0.03), during the first week of treatment. Individuals with CLS also received more intense immunosuppression. Conclusion: CLS was a common complication of MIS-C in our study and these patients had a more severe disease course that required more intensive treatment.
Language	English
Publishing date	2024-02-19
Publishing country	Norway
Document type	Journal Article
ZDB-ID	203487-6
ISSN	1651-2227 ; 0365-1436 ; 0803-5253
ISSN (online)	1651-2227
ISSN	0365-1436 ; 0803-5253
DOI	10.1111/apa.17162
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Article: Identification of novel autoantigens as potential biomarkers in juvenile idiopathic arthritis associated uveitis.

Arve-Butler, Sabine / Mossberg, Anki / Kahn, Fredrik / Najibi, Seyed Morteza / Berthold, Elisabet / Król, Petra / Månsson, Bengt / Kahn, Robin

Frontiers in pediatrics

2023 Volume 10, Page(s) 1091308

Abstract: Background: Many children with juvenile idiopathic arthritis (JIA) have autoantibodies, targeting nuclear components (anti-nuclear antibodies, ANA). ANA in JIA is associated with uveitis, an eye inflammation which may cause permanent vision impairment ... ...

Abstract	Background: Many children with juvenile idiopathic arthritis (JIA) have autoantibodies, targeting nuclear components (anti-nuclear antibodies, ANA). ANA in JIA is associated with uveitis, an eye inflammation which may cause permanent vision impairment if not detected and treated. However, ANA-testing is neither specific nor sensitive enough to be a clinically reliable predictor of uveitis risk, and the precise autoantigens targeted by ANA in JIA are largely unknown. If identified, specific autoantibodies highly associated with uveitis could be used as biomarkers to facilitate identification of JIA patients at risk. Methods: Antibodies from six ANA-positive, oligoarticular JIA patients, with and without uveitis, were explored by two large-scale methods: (1) screening against 42,100 peptides on an autoimmunity profiling planar array, and (2) immunoprecipitations from cell lysates with antigen identification by mass spectrometry. Three hundred thirty-five peptide antigens, selected from proteins identified in the large-scale methods and the scientific literature were investigated using a bead-based array in a cohort of 56 patients with oligoarticular- or RF-negative polyarticular JIA, eight of which were having current or previous uveitis. Results: In the planar array, reactivity was detected against 332 peptide antigens. The immunoprecipitations identified reactivity towards 131 proteins. Only two proteins were identified by both methods. In the bead-based array of selected peptide antigens, patients with uveitis had a generally higher autoreactivity, seen as higher median fluorescence intensity (MFI) across all antigens, compared to patients without uveitis. Reactivity towards 17 specific antigens was significantly higher in patients with uveitis compared to patients without uveitis. Hierarchical clustering revealed that patients with uveitis clustered together. Conclusion: This study investigated autoantigens in JIA and uveitis, by combining two exploratory methods and confirmation in a targeted array. JIA patients with current or a history of uveitis had significantly higher reactivity towards 17 autoantigens and a generally higher autoreactivity compared to JIA patients without uveitis. Hierarchical clustering suggests that a combination of certain autoantibodies, rather than reactivity towards one specific antigen, is associated with uveitis. Our analysis of autoantibodies associated with uveitis in JIA could be a starting point for identification of prognostic biomarkers useful in JIA clinical care.
Language	English
Publishing date	2023-01-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2711999-3
ISSN	2296-2360
ISSN	2296-2360
DOI	10.3389/fped.2022.1091308
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Article ; Online: Neutrophils Lose the Capacity to Suppress T Cell Proliferation Upon Migration Towards Inflamed Joints in Juvenile Idiopathic Arthritis.

Arve-Butler, Sabine / Mossberg, Anki / Schmidt, Tobias / Welinder, Charlotte / Yan, Hong / Berthold, Elisabet / Król, Petra / Kahn, Robin

Frontiers in immunology

2022 Volume 12, Page(s) 795260

Abstract: Neutrophils are highly abundant in synovial fluid of rheumatic inflamed joints. In oligoarticular juvenile idiopathic arthritis (JIA), synovial fluid neutrophils have impaired effector functions and altered phenotype. We hypothesized that these ... ...

Abstract	Neutrophils are highly abundant in synovial fluid of rheumatic inflamed joints. In oligoarticular juvenile idiopathic arthritis (JIA), synovial fluid neutrophils have impaired effector functions and altered phenotype. We hypothesized that these alterations might impact the immunoregulatory interplay between neutrophils and T cells. In this study we analyzed the suppressive effect of neutrophils, isolated from blood and synovial fluid of oligoarticular JIA patients, on CD4
MeSH term(s)	Adolescent ; Arthritis, Juvenile/etiology ; Arthritis, Juvenile/metabolism ; Arthritis, Juvenile/pathology ; Biomarkers ; Cell Communication/immunology ; Cell Movement/immunology ; Cells, Cultured ; Child ; Child, Preschool ; Female ; Humans ; Immunomodulation ; Lymphocyte Activation/immunology ; Male ; Neutrophils/immunology ; Neutrophils/metabolism ; Phenotype ; Proteome ; Proteomics/methods ; Reactive Oxygen Species/metabolism ; Respiratory Burst ; Synovial Fluid/metabolism ; T-Lymphocyte Subsets/metabolism ; T-Lymphocytes/immunology ; T-Lymphocytes/metabolism
Chemical Substances	Biomarkers ; Proteome ; Reactive Oxygen Species
Language	English
Publishing date	2022-01-13
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.2021.795260
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Article ; Online: Synovial monocytes contribute to chronic inflammation in childhood-onset arthritis via IL-6/STAT signalling and cell-cell interactions.

Schmidt, Tobias / Dahlberg, Alma / Berthold, Elisabet / Król, Petra / Arve-Butler, Sabine / Rydén, Emilia / Najibi, Seyed Morteza / Mossberg, Anki / Bengtsson, Anders A / Kahn, Fredrik / Månsson, Bengt / Kahn, Robin

Frontiers in immunology

2023 Volume 14, Page(s) 1190018

Abstract: Introduction: Monocytes are key effector cells in inflammatory processes. We and others have previously shown that synovial monocytes in childhood-onset arthritis are activated. However, very little is known about how they contribute to disease and ... ...

Abstract	Introduction: Monocytes are key effector cells in inflammatory processes. We and others have previously shown that synovial monocytes in childhood-onset arthritis are activated. However, very little is known about how they contribute to disease and attain their pathological features. Therefore, we set out to investigate the functional alterations of synovial monocytes in childhood-onset arthritis, how they acquire this phenotype, and whether these mechanisms could be used to tailorize treatment. Methods: The function of synovial monocytes was analysed by assays believed to reflect key pathological events, such as T-cell activation-, efferocytosis- and cytokine production assays using flow cytometry in untreated oligoarticular juvenile idiopathic arthritis (oJIA) patients (n=33). The effect of synovial fluid on healthy monocytes was investigated through mass spectrometry and functional assays. To characterize pathways induced by synovial fluid, we utilized broad-spectrum phosphorylation assays and flow cytometry, as well as inhibitors to block specific pathways. Additional effects on monocytes were studied through co-cultures with fibroblast-like synoviocytes or migration in transwell systems. Results: Synovial monocytes display functional alterations with inflammatory and regulatory features, e.g., increased ability to induce T-cell activation, resistance to cytokine production following activation with LPS and increased efferocytosis. Conclusions: Synovial monocytes in childhood-onset arthritis are functionally affected and contribute to chronic inflammation, e.g.,
MeSH term(s)	Humans ; Arthritis, Juvenile ; Interleukin-6/metabolism ; Monocytes ; Inflammation ; Cytokines/metabolism ; Cell Communication
Chemical Substances	Interleukin-6 ; Cytokines
Language	English
Publishing date	2023-05-22
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.2023.1190018
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Article ; Online: The Vasculopathy of Juvenile Dermatomyositis: Endothelial Injury, Hypercoagulability, and Increased Arterial Stiffness.

Papadopoulou, Charalampia / Hong, Ying / Krol, Petra / Al Obaidi, Muthana / Pilkington, Clarissa / Wedderburn, Lucy R / Brogan, Paul A / Eleftheriou, Despina

Arthritis & rheumatology (Hoboken, N.J.)

2021 Volume 73, Issue 7, Page(s) 1253–1266

Abstract: Objective: Vasculopathy is considered central to the pathogenesis of juvenile dermatomyositis (DM) and is associated with severe extramuscular manifestations. We undertook this study to investigate the hypothesis that the vasculopathy of juvenile DM can ...

Abstract	Objective: Vasculopathy is considered central to the pathogenesis of juvenile dermatomyositis (DM) and is associated with severe extramuscular manifestations. We undertook this study to investigate the hypothesis that the vasculopathy of juvenile DM can be noninvasively tracked by examining biomarkers of endothelial injury, subclinical inflammation, hypercoagulability, and vascular arterial stiffness. Methods: The study population was a UK cohort of children with juvenile DM. Circulating endothelial cells (CECs) and microparticles (MPs) were identified using immunomagnetic bead extraction and flow cytometry, respectively. Plasma thrombin generation was determined using a fluorogenic assay. Cytokine and chemokine levels were measured by electrochemiluminescence. Arterial stiffness was assessed using pulse wave velocity (PWV). Results were expressed as the median and interquartile range (IQR), and statistical significance was assessed using nonparametric analyses. Results: Ninety patients with juvenile DM and 79 healthy control subjects were included. The median age of the patients was 10.21 years (IQR 6.68-13.40), and the median disease duration was 1.63 years (IQR 0.28-4.66). CEC counts were higher in all patients with juvenile DM compared to controls (median 96 cells/ml [IQR (40-192] and 12 cells/ml [IQR 8-24], respectively; P < 0.0001). Circulating MP numbers were also significantly higher in patients with active juvenile DM compared to controls (median 204.7 × 10 Conclusion: We observed increased endothelial injury and increased levels of proinflammatory cytokines in patients with active juvenile DM. MP profiles reflected distinct disease activity status in juvenile DM and are markers of vascular pathology, platelet activation, and thrombotic propensity. Ongoing long-term vascular injury may result in increased arterial stiffness in patients with juvenile DM.
MeSH term(s)	Adolescent ; Case-Control Studies ; Cell-Derived Microparticles/metabolism ; Chemokines/blood ; Child ; Cytokines/blood ; Dermatomyositis/blood ; Dermatomyositis/physiopathology ; Endothelial Cells/metabolism ; Endothelium/physiopathology ; Female ; Humans ; Male ; Pulse Wave Analysis ; Thrombin/metabolism ; Thrombophilia/blood ; Thrombophilia/physiopathology ; Vascular Diseases/blood ; Vascular Diseases/physiopathology ; Vascular Stiffness/physiology
Chemical Substances	Chemokines ; Cytokines ; Thrombin (EC 3.4.21.5)
Language	English
Publishing date	2021-05-28
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2756371-6
ISSN	2326-5205 ; 2326-5191
ISSN (online)	2326-5205
ISSN	2326-5191
DOI	10.1002/art.41639
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Article ; Online: Risk factors for multisystem inflammatory syndrome in children - A population-based cohort study of over 2 million children.

Rhedin, Samuel / Lundholm, Cecilia / Horne, AnnaCarin / Smew, Awad I / Osvald, Emma Caffrey / Haddadi, Araz / Alfvén, Tobias / Kahn, Robin / Król, Petra / Brew, Bronwyn Haasdyk / Almqvist, Catarina

The Lancet regional health. Europe

2022 Volume 19, Page(s) 100443

Abstract: Background: Although severe acute COVID-19 is rare in children, SARS-CoV-2 infection can trigger the novel post-infectious condition multisystem inflammatory syndrome in children (MIS-C). Increased knowledge on risk factors for MIS-C could improve our ... ...

Abstract	Background: Although severe acute COVID-19 is rare in children, SARS-CoV-2 infection can trigger the novel post-infectious condition multisystem inflammatory syndrome in children (MIS-C). Increased knowledge on risk factors for MIS-C could improve our understanding of the pathogenesis of the condition and better guide targeted public health interventions. The aim of the study was to assess risk factors for MIS-C with the aim to identify vulnerable children. Methods: A register-based cohort study including all children and adolescents <19 years born in Sweden between March 1, 2001- December 31, 2020 was performed. Data on sociodemographic risk factors and comorbidities (sex, age, parental region of birth, parental education, asthma, autoimmune disease, chromosomal anomalies, chronic heart disease, chronic lung disease, obesity, life-limiting condition) were retrieved from national health and population registers. The outcome was MIS-C diagnosis according to the Swedish Pediatric Rheumatology Quality Register during March 1, 2020 - December 8, 2021.Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox regression analysis. Incidence rates per 100 000 person-years were calculated assuming a Poisson distribution. Findings: Among 2 117 443 children included in the study, 253 children developed MIS-C, corresponding to an incidence rate of 6·8 (95% CI: 6·0-7·6) per 100 000 person-years. Male sex (HR 1·65, 95% CI: 1·28-2·14), age 5-11 years (adjusted HR 1·44, 95% CI: 1·06-1·95 using children 0-4 years as reference), foreign-born parents (HR 2·53, 95% CI: 1·93-3·34), asthma (aHR 1·49, 95% CI: 1·00-2·20), obesity (aHR 2·15, 95% CI: 1·09-4·25) and life-limiting conditions (aHR 3·10, 95% CI: 1·80-5·33) were associated with MIS-C. Children 16-18 years had a reduced risk for MIS-C (aHR 0·45, 95% CI: 0·24-0·85). Interpretation: We report increased risks for MIS-C in children with male sex, age 5-11 years, foreign-born parents, asthma, obesity, and life-limiting condition. Knowing these risk populations might facilitate identification of children with MIS-C and potentially guide targeted public health interventions. Nevertheless, the absolute risks for MIS-C were very low. Funding: Financial support was provided from the Swedish Research Council (grant no 2018-02640), the Swedish Heart-Lung Foundation (grant no 20210416), the Asthma and Allergy Association, Ake Wiberg foundation, the Samariten Foundation, the Society of Child Care, and Region Stockholm.
Language	English
Publishing date	2022-06-22
Publishing country	England
Document type	Journal Article
ISSN	2666-7762
ISSN (online)	2666-7762
DOI	10.1016/j.lanepe.2022.100443
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Article ; Online: PFAPA syndrome in the Czech Republic

Król Petra / Böhm Marek / Nemcová Dana / Doležalová Pavla

Pediatric Rheumatology, Vol 10, Iss Suppl 1, p A

a single-centre experience

2012 Volume 85

Keywords	Diseases of the musculoskeletal system ; RC925-935 ; Specialties of internal medicine ; RC581-951 ; Internal medicine ; RC31-1245 ; Medicine ; R ; DOAJ:Internal medicine ; DOAJ:Medicine (General) ; DOAJ:Health Sciences ; Pediatrics ; RJ1-570 ; DOAJ:Pediatrics
Language	English
Publishing date	2012-07-01T00:00:00Z
Publisher	BioMed Central
Document type	Article ; Online
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Article: PFAPA syndrome: clinical characteristics and treatment outcomes in a large single-centre cohort.

Król, Petra / Böhm, Marek / Sula, Viktor / Dytrych, Petra / Katra, Rami / Nemcová, Dana / Dolezalová, Pavla

Clinical and experimental rheumatology

2013 Volume 31, Issue 6, Page(s) 980–987

Abstract: Objectives: This paper aims to describe clinical and laboratory features and disease outcome in a single-centre cohort of patients with PFAPA syndrome (Periodic Fever, Aphtous stomatitis, Pharyngitis, and Adenitis) and to test performance of diagnostic ... ...

Abstract	Objectives: This paper aims to describe clinical and laboratory features and disease outcome in a single-centre cohort of patients with PFAPA syndrome (Periodic Fever, Aphtous stomatitis, Pharyngitis, and Adenitis) and to test performance of diagnostic and therapeutic algorithms. Methods: Patients fulfilling criteria were selected from the fever clinic population. Prospective follow-up together with recruitment of newly diagnosed patients followed pre-defined guidelines. Diagnostic and therapeutic algorithms and definitions of outcome and therapy response were formulated. Paired blood samples during febrile and afebrile periods were compared. Results: Out of 176 patients referred for suspected periodic fever 125 children fulfilled criteria. Their age at onset was 23 months, median episode duration 3.5 days at 4-week intervals. Fever was associated with pharyngitis (91%), cervical adenitis (78%) and aphtae (41%). Among therapeutic options, episodic prednisone proved to be the most common first-line treatment. Administered to 77 patients, it reduced symptoms in 94%. Tonsillectomy led to the full symptom resolution in all 18 patients. Forty-six patients reached disease remission. Conclusions: Distribution of typical symptoms, response to therapies and disease outcome in a large patient cohort were documented. We offer diagnostic and therapeutic algorithms that have proven effective during this prospective trial. Our findings support the general belief of benign nature of this aetiologically unclear condition, despite proportion of patients having persistent disease for years. Maintenance of normal findings in afebrile intervals, striking response to a single dose of prednisone and normal growth and development together with spontaneous tendency towards prolongation of afebrile intervals are important confirmatory features of PFAPA syndrome.
MeSH term(s)	Age of Onset ; Algorithms ; Child, Preschool ; Clinical Protocols ; Czech Republic/epidemiology ; Female ; Fever/diagnosis ; Fever/epidemiology ; Fever/therapy ; Glucocorticoids/therapeutic use ; Humans ; Infant ; Lymphadenitis/diagnosis ; Lymphadenitis/epidemiology ; Lymphadenitis/therapy ; Male ; Pharyngitis/diagnosis ; Pharyngitis/epidemiology ; Pharyngitis/therapy ; Prednisone/therapeutic use ; Prospective Studies ; Recurrence ; Stomatitis, Aphthous/diagnosis ; Stomatitis, Aphthous/epidemiology ; Stomatitis, Aphthous/therapy ; Syndrome ; Time Factors ; Tonsillectomy ; Treatment Outcome
Chemical Substances	Glucocorticoids ; Prednisone (VB0R961HZT)
Language	English
Publishing date	2013-11
Publishing country	Italy
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	605886-3
ISSN	1593-098X ; 0392-856X
ISSN (online)	1593-098X
ISSN	0392-856X
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Article ; Online: Population-based study of multisystem inflammatory syndrome associated with COVID-19 found that 36% of children had persistent symptoms.

Kahn, Robin / Berg, Stefan / Berntson, Lillemor / Berthold, Elisabet / Brodin, Petter / Bäckström, Fredrik / Compagno, Michele / Fasth, Anders / Lingman Framme, Jenny / Horne, AnnaCarin / Hätting, Josefin / Król, Petra / Kukka, Antti J / Mossberg, Maria / Månsson, Bengt / Nordenhäll, Charlotta / Idring Nordström, Selma / Khammari Nyström, Fatine / Palmblad, Karin /

Rasti, Reza / Rudolph, André / Rydenman, Karin / Sundberg, Erik / Säve-Söderbergh, Eva / Altman, Maria

Acta paediatrica (Oslo, Norway : 1992)

2021 Volume 111, Issue 2, Page(s) 354–362

Abstract: Aim: Our aim was to describe the outcomes of multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19.: Methods: This national, population-based, longitudinal, multicentre study used Swedish data that were prospectively ... ...

Abstract	Aim: Our aim was to describe the outcomes of multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19. Methods: This national, population-based, longitudinal, multicentre study used Swedish data that were prospectively collected between 1 December 2020 and 31 May 2021. All patients met the World Health Organization criteria for MIS-C. The outcomes 2 and 8 weeks after diagnosis are presented, and follow-up protocols are suggested. Results: We identified 152 cases, and 133 (87%) participated. When followed up 2 weeks after MIS-C was diagnosed, 43% of the 119 patients had abnormal results, including complete blood cell counts, platelet counts, albumin levels, electrocardiograms and echocardiograms. After 8 weeks, 36% of 89 had an abnormal patient history, but clinical findings were uncommon. Echocardiogram results were abnormal in 5% of 67, and the most common complaint was fatigue. Older children and those who received intensive care were more likely to report symptoms and have abnormal cardiac results. Conclusion: More than a third (36%) of the patients had persistent symptoms 8 weeks after MIS-C, and 5% had abnormal echocardiograms. Older age and higher levels of initial care appeared to be risk factors. Structured follow-up visits are important after MIS-C.
MeSH term(s)	Adolescent ; Aged ; COVID-19/complications ; Child ; Critical Care ; Echocardiography ; Humans ; SARS-CoV-2 ; Systemic Inflammatory Response Syndrome
Language	English
Publishing date	2021-12-01
Publishing country	Norway
Document type	Journal Article ; Multicenter Study
ZDB-ID	203487-6
ISSN	1651-2227 ; 0365-1436 ; 0803-5253
ISSN (online)	1651-2227
ISSN	0365-1436 ; 0803-5253
DOI	10.1111/apa.16191
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Article: Polyclonal, newly derived T cells with low expression of inhibitory molecule PD-1 in tonsils define the phenotype of lymphocytes in children with Periodic Fever, Aphtous Stomatitis, Pharyngitis and Adenitis (PFAPA) syndrome

Petra, Dytrych / Dolezalova Pavla / Fronkova Eva / Hrusak Ondrej / Hubacek Petr / Kabelka Zdenek / Kalina Tomas / Katra Rami / Kotrova Michaela / Krol Ladislav / Krol Petra / Kuzilkova Daniela

Molecular Immunology. 2015 May, v. 65

2015

Abstract: PFAPA syndrome is a benign, recurrent inflammatory disease of childhood. Tonsillectomy is one of the therapeutic options with a yet unexplained biological mechanism. We tested whether specific lymphocyte subsets recruited from blood to human tonsils ... ...

Abstract	PFAPA syndrome is a benign, recurrent inflammatory disease of childhood. Tonsillectomy is one of the therapeutic options with a yet unexplained biological mechanism. We tested whether specific lymphocyte subsets recruited from blood to human tonsils participate in PFAPA pathogenesis.Paired tonsils/peripheral blood (PB) samples were investigated (a) from children with PFAPA that successfully resolved after tonsillectomy (n=10) (b) from children with obstructive sleep apnoea syndrome as controls (n=10). The lymphocyte profiles were analysed using 8-colour flow cytometry, immunoglobulin (IGH) and T-cell receptor (TCR) gene rearrangements via PCR and next generation sequencing; a TREC/KREC analysis was performed using qPCR.The PFAPA tonsils in the asymptomatic phase had a lower percentage of B-lymphocytes than controls; T-lymphocyte counts were significantly higher in PB. The percentages of cytotoxic CD8pos T-lymphocytes were approximately 2-fold higher in PFAPA tonsils; the transitional B cells and naÃ¯ve stages of both the CD4pos and CD8pos T-lymphocytes with a low expression of PD-1 molecule and high numbers of TREC were also increased. With the exception of elevated plasmablasts, no other differences were significant in PB. The expression levels of CXCL10, CXCL9 and CCL19 genes were significantly higher in PFAPA tonsils. The IGH/TCR pattern showed no clonal/oligoclonal expansion. DNA from the Epstein-Barr virus, Human Herpervirus-6 or adenovirus was detected in 7 of 10 PFAPA tonsils but also in 7 of 9 controls.Our findings suggest that the uninhibited, polyclonal response of newly derived lymphocytes participate in the pathogenesis of PFAPA. Because most of the observed changes were restricted to tonsils and were not present in PB, they partly explain the therapeutic success of tonsillectomy in PFAPA syndrome.
Keywords	B-lymphocytes ; chemokine CCL19 ; chemokine CXCL10 ; chemokine CXCL9 ; childhood ; children ; cytotoxicity ; DNA ; fever ; flow cytometry ; genes ; high-throughput nucleotide sequencing ; Human herpesvirus 4 ; humans ; immunoglobulin A ; pathogenesis ; pharyngitis ; phenotype ; polymerase chain reaction ; sleep ; T-lymphocytes ; tonsils
Language	English
Dates of publication	2015-05
Size	p. 139-147.
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	424427-8
ISSN	1872-9142 ; 0161-5890
ISSN (online)	1872-9142
ISSN	0161-5890
DOI	10.1016/j.molimm.2015.01.004
Database	NAL-Catalogue (AGRICOLA)

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