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Yanfang Jiang - One of the best experts on this subject based on the ideXlab platform.
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distinct phenotypic subpopulations of circulating cd4 cxcr5 follicular helper t cells in children with active IgA Vasculitis
BMC Immunology, 2016Co-Authors: Jinghua Wang, Sirui Yang, Yanfang JiangAbstract:Background Circulating follicular helper T (Tfh) cells are a heterogeneous population of CD4+ helper T cells that promotes pathogenic immune responses in autoimmune diseases. In this study, we examined the status of different subpopulations of Tfh cells in peripheral circulation and their associations with various clinical characteristics of IgA Vasculitis (IgAV).
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distinct phenotypic subpopulations of circulating cd4 cxcr5 follicular helper t cells in children with active IgA Vasculitis
BMC Immunology, 2016Co-Authors: Deying Liu, Jinghua Wang, Sirui Yang, Jinxiang Liu, Congcong Liu, Yanfang JiangAbstract:Circulating follicular helper T (Tfh) cells are a heterogeneous population of CD4+ helper T cells that promotes pathogenic immune responses in autoimmune diseases. In this study, we examined the status of different subpopulations of Tfh cells in peripheral circulation and their associations with various clinical characteristics of IgA Vasculitis (IgAV). According to the phenotypic expressions of different molecules, focus was given on six subpopulations of Tfh cells: CD4+CXCR5+, CD4+CXCR5+ICOS+, CD4+CXCR5+ICOS+PD-1+, CD4+CXCR5+ICOShighPD-1high, CD4+CXCR5+ICOS−PD-1+, and CXCR5+CD45RA−IL-21+. The frequencies of these six subpopulations and the circulating level of Tfh-related cytokine interleukin 21 (IL-21) were measured from 27 patients with IgAV and 15 healthy controls (HC) by flow cytometry and flow cytometric bead array, respectively. Significantly higher frequencies of CD4+CXCR5+, CD4+CXCR5+ICOS+, CD4+CXCR5+ICOS+PD-1+, CD4+CXCR5+ICOShighPD-1high and CXCR5+CD45RA−IL-21+ Tfh cells, as well as higher levels of plasma IL-21, were detected in IgAV patients compared to HC. The level of each Tfh subpopulation varied by the presenting symptoms of IgAV, but did not differ between patients treated or not treated with glucocorticoids. When the disease entered the remission stage following treatment, circulating levels of CD4+CXCR5+, CD4+CXCR5+ICOS+, CD4+CXCR5+ICOS+PD-1+, CD4+CXCR5+ICOShighPD-1high and CXCR5+CD45RA−IL-21+ Tfh cells, as well as plasma IL-21 levels were reduced. Among the six subpopulations of Tfh cells, both CD4+CXCR5+ICOS+ and CXCR5+CD45RA−IL-21+ significantly and positively correlated with serum IgA and plasma IL-21 levels, but only CXCR5+CD45RA−IL-21+ significantly and negatively correlated with the serum C4 level. Tfh cells may differentially contribute to the development of IgAV or predict disease progression. These findings provide novel insights in the pathogenesis of IgAV and may benefit treatment development targeting organ-specific presenting symptoms of IgAV.
Matthew J Koster - One of the best experts on this subject based on the ideXlab platform.
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sat0277 head and neck involvement of IgA Vasculitis a case control study
Annals of the Rheumatic Diseases, 2020Co-Authors: Villatoro M Villar, David A. Wetter, Cynthia S Crowson, Kenneth J Warrington, Matthew J KosterAbstract:Background: IgA Vasculitis (IgAV) is an immune-complex mediated, small-vessel Vasculitis which predominantly involves the skin on the lower extremities. Head and neck involvement is rarely reported. Objectives: To describe the presentation and outcome of a series of patients with head and/or neck involvement in comparison to patients with cutaneous findings isolated to the lower extremities. Methods: Patients with biopsy-proven IgAV from January 1, 1997 through December 31, 2016 were retrospectively identified through direct medical chart review. IgAV was diagnosed in accordance with the American College of Rheumatology (ACR) and the European League Against Rheumatism/ Paediatric Rheumatology European Society/Paediatric Rheumatology International Trials Organisation (EULAR/PRINTO/PRES) criteria. Among this cohort, patients with documented clinical, photographic, or histologic descriptions of vasculitic skin lesions affecting the head or neck were compiled. Each patient with head/neck (H/N) involvement of IgAV (case) was matched to two age- and sex-matched control patients with IgAV for which the cutaneous features were isolated to the waistline or distal. Baseline characteristics, laboratory parameters, treatments and outcome were collected by a physician abstractor. Results: Thirteen patients with H/N-IgAV involvement were identified. Baseline characteristics of the cases and controls are demonstrated in Table 1. H/N involvement included facial (cheeks, forehead) [n=6], perioral/oral/lip [n=6], auricular [n=2], nasal [n=2], and neck [n=1]. All patients in both groups had evidence of purpuric skin lesions. Patients with H/N-IgAV involvement more frequently had evidence of skin ulcerations (23% vs. 0%; p=0.01) [Figure 1]. Overall baseline renal involvement and microscopic hematuria were less commonly observed in patients with H/N-IgAV. Among H/N-IgAV cases, at last follow-up all had resolution of H/N lesions but 3 of 13 had persistent skin lesions on the lower extremities despite ongoing treatment. Long-term outcome between cases and controls did not identify any significant differences in the development of end-stage renal disease, time to resolution of hematuria or proteinuria, time to complete IgAV response, or time to first IgAV relapse. Conclusion: This study reports the largest series of patients with head/neck involvement of IgA, a rarely reported entity. In this cohort, patients with H/N-IgAV had less frequent renal involvement compared to IgAV patients with lower extremity only skin lesions. Clinicians should be aware of atypical locations of IgAV involvement. Additional research is needed to further understand this clinical subset. Disclosure of Interests: Michel Villatoro Villar: None declared, David A. Wetter: None declared, Cynthia S. Crowson Grant/research support from: Pfizer research grant, Kenneth J Warrington: None declared, Matthew Koster: None declared
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clinical characteristics of biopsy proven IgA Vasculitis in children and adults a retrospective cohort study
Mayo Clinic proceedings, 2019Co-Authors: Michel Villatorovillar, Cynthia S Crowson, Kenneth J Warrington, Ashima Makol, Steven R Ytterberg, Matthew J KosterAbstract:Abstract Objective To describe the differences in clinical characteristics and outcome between adult- and childhood-onset biopsy-proven IgA Vasculitis (IgAV) in North America. Patients and Methods Patients with IgAV diagnosed from January 1, 1997, through December 31, 2016, were retrospectively identified. Data were abstracted from direct medical record review. Kaplan-Meier methods were used to estimate survival rates. Results A total of 243 patients with IgAV were included (227 [93.4%] white, 141 [58.0%] male); 174 patients were adults (≥21 years), and 69 were younger than 21 years. Compared with patients younger than 21 years, adults at baseline more frequently had ulcerative skin lesions (19 [10.9%] vs 1 [1.4%]; P=.02) and nephrotic-range proteinuria (21 of 96 [21.9%] vs 1 of 38 [2.6%]; P=.007) but less commonly had abdominal pain (59 [33.9%] vs 42 [60.9%]; P Conclusion IgA Vasculitis in adults is associated with more severe skin/kidney involvement and poorer renal outcome. Among adults with IgAV, patients aged 51 years or older at diagnosis have significantly higher mortality (P
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thu0322 clinical characteristics of biopsy proven IgA Vasculitis in children and adults a retrospective cohort study
Annals of the Rheumatic Diseases, 2019Co-Authors: Michel Villatoro Villar, Cynthia S Crowson, Kenneth J Warrington, Ashima Makol, Steven R Ytterberg, Matthew J KosterAbstract:Background Differences in both presentation and outcome based on age of diagnosis have been described in patients with IgA Vasculitis (IgAV) but data are limited due to cohort size and follow-up duration. Objectives To describe the differences in clinical characteristics and outcome between adult- and child-onset biopsy-proven IgA Vasculitis (IgAV) in North America. Methods Patients with IgAV from January 1, 1997, through December 31, 2016 were retrospectively identified. Clinical characteristics, laboratory parameters and outcomes were abstracted from direct medical chart review. Proteinuria was classified as non-nephrotic (≥0.2 g/d, ≤3.5 g/d) or nephrotic (>3.5 g/d). Microscopic hematuria was defined as ≥5 RBCs/hpf or ≥2+ on dipstick. Disease activity at each follow-up visit was categorized as complete response (normalization of all baseline abnormalities due to IgAV), partial response, non-response (lack of improvement of any abnormalities) or relapse (development of clinical signs of IgAV after a symptom-free period of at least one month). Prevalence of disease activity and competing risks were estimated using multi-state models. Results A total of 243 IgAV patients were identified (97% Caucasian, 58% male). 174 patients were adults (>21 years) and 69 were Dialysis was required in 13 patients (8 adults) and renal transplant was performed in 4 cases (1 adult). Of 137 patients with hematuria during the study, 72% had complete resolution by 1 year after onset, compared to 50% of 179 patients with proteinuria. The prevalence of disease activity state at each follow-up time point is shown in figure 1. During 389 person-years of follow-up, 29 deaths were observed. The main causes of death were cancer, cardiovascular disease, infection and Vasculitis. Five year survival rates (95% CI) for patients aged Conclusion IgAV in adults is associated with more severe skin/kidney involvement and poorer renal outcome. Among adults with IgAV, patients aged 51 years or older at diagnosis have significantly higher mortality. References [1] Audemard-Verger A, Terrier B, Dechartres A, et al. Characteristics and Management of IgA Vasculitis (Henoch-Schonlein) in Adults: Data From 260 Patients Included in a French Multicenter Retrospective Survey. Arthritis & rheumatology (Hoboken, N.J.). 2017;69:1862-1870. [2] Pillebout E, Thervet E, Hill G, Alberti C, Vanhille P, Nochy D. Henoch-Schonlein Purpura in adults: outcome and prognostic factors. Journal of the American Society of Nephrology : JASN. 2002;13:1271-1278. [3] Westman K, Flossmann O, Gregorini G. The long-term outcomes of systemic Vasculitis. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2015;30 Suppl 1:i60-66. [4] Shrestha S, Sumingan N, Tan J, Alhous H, McWilliam L, Ballardie F. Henoch Schonlein purpura with nephritis in adults: adverse prognostic indicators in a UK population. QJM : monthly journal of the Association of Physicians. 2006;99:253-265. Disclosure of Interests None declared
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sat0249 IgA Vasculitis associated with inflammatory bowel disease a retrospective study
Annals of the Rheumatic Diseases, 2019Co-Authors: Michel Villatoro Villar, Cynthia S Crowson, Kenneth J Warrington, Ashima Makol, Steven R Ytterberg, Matthew J KosterAbstract:Background: Leukocytoclastic Vasculitis has been reported in patients with inflammatory bowel disease (IBD) but cases of IgA Vasculitis (IgAV) in IBD are considered rare. Objectives: The purpose of this study was to describe the baseline characteristics and outcome of a series of patients with IBD and IgAV. Methods: Biopsy-proven IgAV-patients with prior history of IBD were identified retrospectively at Mayo Clinic, Rochester, MN. Data were abstracted from direct medical chart review. Each IBD-IgAV case was matched to two controls with IgAV but without IBD history based on age, sex and baseline renal function at time of IgAV onset. Results: A total of 9 patients were included in the study group (6 male, 3 female). Crohn’s disease (CD) and Ulcerative Colitis (UC) were present in 7 and 2 patients, respectively. The mean length of time between IBD diagnosis and onset of IgAV was 17.3±19.9 years. For patients on biologic treatment for IBD, the mean length of time between initiation of biologic and onset of IgAV was 3.3±3.8 years (range 0-12 years). Active IBD at IgAV-onset was present in 56% (5/9) of patients. Tumor necrosis factor inhibitors (TNFi) were the most frequent biologics used for IBD (8, 89%); infliximab was the most common (7, 78%). At IgAV-onset, only 5 patients were on treatment with TNFi; two subsequently discontinued, two switched to another TNFi (adalimumab), and one patient continued. At last follow-up, two of three patients that remained on TNFi had full resolution of IgAV despite ongoing TNFi use. Comparison of baseline characteristics between cases with IBD-IgAV and matched non-IBD IgAV controls is demonstrated in Table 1. No differences were seen in regards to development of end-stage renal disease, resolution of hematuria and/or proteinuria, time to complete IgAV response or first IgAV relapse. Conclusion: Baseline characteristics and outcomes of patients with IBD-IgAV are similar to those with IgAV without IBD. Development of IgAV is not limited to patients with clinically active IBD. Whether use of TNFi is related to the pathogenesis of IgAV in some patients with IBD remains unclear. Further research into the pathophysiologic connection between IBD and IgAV is needed. References [1] Saint Marcoux B, De Bandt M. Vasculitides induced by TNFalpha antagonists: a study in 39 patients in France. Joint, bone, spine : revue du rhumatisme. 2006;73(6):710-3. [2] Sy A, Khalidi N, Dehghan N, Barra L, Carette S, Cuthbertson D, et al. Vasculitis in patients with inflammatory bowel diseases: A study of 32 patients and systematic review of the literature. Seminars in arthritis and rheumatism. 2016;45(4):475-82. [3] Ko JS, Uberti G, Napekoski K, Patil DT, Billings SD. Cutaneous manifestations in inflammatory bowel disease: a single institutional study of non-neoplastic biopsies over 13 years. Journal of cutaneous pathology. 2016;43(11):946-55. [4] Ozen S, Pistorio A, Iusan SM, Bakkaloglu A, Herlin T, Brik R, et al. EULAR/PRINTO/PRES criteria for Henoch-Schonlein purpura, childhood polyarteritis nodosa, childhood Wegener granulomatosis and childhood Takayasu arteritis: Ankara 2008. Part II: Final classification criteria. Ann Rheum Dis. 2010;69(5):798-806. [5] Laresche C, Locatelli F, Biver-Dalle C, Nachury M, Heyd B, Koch S, et al. Severe Henoch-Schonlein purpura complicating infliximab therapy for ulcerative colitis. Cutis. 2017;99(1):E20-e2. Disclosure of Interests: None declared
Evangeline Pillebout - One of the best experts on this subject based on the ideXlab platform.
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covid 19 related IgA Vasculitis
Arthritis & Rheumatism, 2020Co-Authors: Matthieu Allez, Blandine Denis, Jeandavid Bouaziz, Maxime Battistella, Anne Marie Zagdanski, Jules Bayart, Ingrid Lazaridou, Caroline Gatey, Evangeline Pillebout, Marie Laure Chaix BaudierAbstract:IgA Vasculitis is a systemic small‐vessel Vasculitis which may be triggered by different microorganisms. IgA Vasculitis cases have been reported in patients with immune‐mediated inflammatory disorders treated with TNF inhibitors. Here we report the case of a young Crohn’s disease patient in clinical remission under adalimumab admitted for an IgA Vasculitis, with an extended ileitis, and a positive PCR testing for Covid‐19. Serum IgA levels were markedly increased and serology for Covid‐19 was weakly positive for IgA. Even if we cannot prove the causality of Covid‐19, it is remarkable to note that this case of IgA Vasculitis was associated with high IgA levels in the serum and the Covid‐19 serology was positive only for IgA.
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gastrointestinal involvement in adult IgA Vasculitis henoch schonlein purpura updated picture from a french multicentre and retrospective series of 260 cases
Rheumatology, 2020Co-Authors: Alexandra Audemardverger, Evangeline Pillebout, Zahir Amoura, Patrice Cacoub, Noemie Jourdechiche, B Lioger, Nihal Martis, Guillaume Moulis, Etienne Riviere, A BaldolliAbstract:Objectives To describe the clinical presentation, treatments and prognosis of gastrointestinal (GI) involvement in adult IgA Vasculitis (IgAV). Methods Data from 260 adults with IgAV included in a French multicentre retrospective survey were analysed. Presentation and outcomes of patients with (GI+) and without (GI-) GI involvement were compared. Results One hundred and thirty-seven (53%) patients had GI involvement. Initial manifestations were abdominal pain in 99%, intestinal bleeding in 31%, diarrhoea in 26% and acute surgical abdomen in only 4%. Abdominal imaging revealed thickening of intestinal wall in 61%, and endoscopies revealed abnormalities in 87%, mostly mucosal ulcerations. GI+ vs GI- patients were younger (46 ± 18 vs 54 ± 18 years; P = 0.0004), had more constitutional symptoms (43% vs 23%; P = 0.0005) and joint involvement (72 vs 50%; P = 0.0002), and higher CRP levels (3.7 vs 1.9 mg/dl; P = 0.001). Clinical response and relapse rates were comparable between groups, and all causes mortality (2 vs 4%) and IgAV-related mortality (1% vs 2%) as well. GI-related deaths were due to intestinal perforation and mesenteric ischaemia. Conclusion GI involvement is frequent in adult IgAV. GI involvement is frequent in adult IgAV. Mortality is not uncommon but does not seem to be specifically related to GI. Immunosuppressants should not be preferred as first-line therapy for GI+ patients but may be required in case of acute surgical abdomen.
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brief report rituximab for the treatment of adult onset IgA Vasculitis henoch schonlein
Arthritis & Rheumatism, 2018Co-Authors: Federica Maritati, Evangeline Pillebout, Roberta Fenoglio, Giacomo Emmi, Maria Letizia Urban, Rossana Rocco, Maria Nicastro, Monia Incerti, Matteo Goldoni, Giorgio TrivioliAbstract:Objective: Adult-onset IgA Vasculitis (Henoch-Schonlein) (IgAV) is a rare systemic Vasculitis characterized by IgA1-dominant deposits. The treatment of adult-onset IgAV is controversial and is based on the combination of glucocorticoids and immunosuppressive agents, but many patients have refractory or relapsing disease despite treatment. Rituximab (RTX) is a B cell–depleting antibody of proven efficacy in antineutrophil cytoplasmic antibody–associated Vasculitis. We undertook this study to test the efficacy and safety of RTX in a multicenter cohort of patients with adult-onset IgAV. Methods: In this multicenter observational study, we included patients with adult-onset IgAV who had received RTX either for refractory/relapsing disease or because they had contraindications to conventional glucocorticoid/immunosuppressive therapy. We analyzed the rates of remission (defined on the basis of the Birmingham Vasculitis Activity Score [BVAS]) and relapse as well as the variations over time in estimated glomerular filtration rate (GFR), proteinuria, C-reactive protein (CRP) level, BVAS, and prednisone dose. Results: Twenty-two patients were included; their median duration of follow-up was 24 months (interquartile range 18–48 months). Sixteen patients received RTX as add-on therapy and 6 as monotherapy. Twenty patients (90.9%) achieved remission, and 7 of those 20 patients (35%) had subsequent relapse of disease. There were significant reductions in 24-hour proteinuria (P < 0.0001), CRP level (P = 0.0005), BVAS (P < 0.0001), and prednisone dose (P < 0.0001) from RTX initiation through the last follow-up visit; estimated GFR remained stable. RTX was generally well tolerated. One patient died after 60 months of follow-up. Conclusion: Our data suggest that RTX is an effective and safe therapeutic option for adult-onset IgAV. (Less)
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biomarkers of IgA Vasculitis nephritis in children
PLOS ONE, 2017Co-Authors: Evangeline Pillebout, Agnes Jamin, Hamza Ayari, Pierre Housset, Melissa Pierre, Virginia Sauvaget, Denis Viglietti, Georges Deschenes, Renato C Monteiro, Laureline BerthelotAbstract:Henoch-Schonlein purpura is a systemic Vasculitis characterized by IgA deposits, which target the skin, joints, and kidneys, among other organs. In children, prognosis is often good but little is known about biomarkers of pediatric nephritis. We hypothesized that biological markers, including cytokines, immunoglobulins, IgA-immune complexes, IgA glycosylation and neutrophil gelatinase-associated lipocalin (NGAL), may discriminate IgA Vasculitis (IgAV) pediatric patients with renal involvement from those without renal involvement. Fifty children at the time of IgAV rash between 2010 and 2015 were prospectively enrolled and compared to 21 controls. All patients were assessed for clinical and biological parameters at the time of diagnosis, including the levels of cytokines, immunoglobulins, immune complexes, IgA glycosylation and NGAL in serum and urine. Among IgAV patients, 33 patients exhibited nephritis (IgAV-N) and 17 children were without nephritis (IgAV-woN). The serum level of galactose-deficient (Gd)-IgA1 (p<0.01) and the urinary concentrations of IgA, IgG, IgM, IL-6, IL-8, IL-10, IgA-IgG complexes and IgA-sCD89 complexes (p<0.001 for all) were higher in the IgAV-N patients than in the IgAV-woN patients. Among those markers, urinary IgA and IgM had the highest AUC (0.86 and 0.87 respectively, p<0.0001). This prospective cohort study furthers our understanding of the pathophysiology of IgAV. We identified biomarkers that are able to distinguish patients initially with or without nephritis. To conclude, serum Gd-IgA1 and urinary IgA, IgG, IgM, IL-6, IL-8, IL-10, and IgA-IgG and IgA-sCD89 complexes could identify IgAV pediatric patients with renal involvement at the time of diagnosis.
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IgA Vasculitis henoch shonlein purpura in adults diagnostic and therapeutic aspects
Autoimmunity Reviews, 2015Co-Authors: Alexandra Audemardverger, Evangeline Pillebout, Loic Guillevin, Eric Thervet, B TerrierAbstract:Abstract Immunoglobulin A (IgA) Vasculitis, formerly called Henoch–Schonlein purpura, is an immune complex Vasculitis affecting small vessels with dominant IgA deposits. Clinical manifestations mainly involve cutaneous purpura, arthralgias and/or arthritis, acute enteritis and glomerulonephritis. IgA Vasculitis is more common among children than adults, with more severe disease in adults. Gastrointestinal and renal involvements represent the principal causes of morbidity and mortality in adults. Factors associated with long-term end-stage renal disease (ESRD) include baseline renal function impairment and baseline proteinuria > 1 or 1.5 g/day, and on renal biopsy degree of interstitial fibrosis, sclerotic glomeruli and fibrinoid necrosis. Management of IgA Vasculitis in adults is rendered difficult for clinicians because of the absence of correlation between initial presentation and long-term renal outcome, and the possible occurrence of spontaneous remission in patients with severe presentation or, in contrast, possible evolution to ESRD in patients with mild symptoms. Treatment is often symptomatic because disease course is usually benign. Treatment of severe involvement, including severe gastrointestinal complications or proliferative glomerulonephritis, remains controversial, with no evidence that corticosteroids or immunosuppressive agents improved long-term outcome. Prospective, randomized, controlled trials are thus needed to analyze the benefit–risk ratio of such treatments.
Jinghua Wang - One of the best experts on this subject based on the ideXlab platform.
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distinct phenotypic subpopulations of circulating cd4 cxcr5 follicular helper t cells in children with active IgA Vasculitis
BMC Immunology, 2016Co-Authors: Jinghua Wang, Sirui Yang, Yanfang JiangAbstract:Background Circulating follicular helper T (Tfh) cells are a heterogeneous population of CD4+ helper T cells that promotes pathogenic immune responses in autoimmune diseases. In this study, we examined the status of different subpopulations of Tfh cells in peripheral circulation and their associations with various clinical characteristics of IgA Vasculitis (IgAV).
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distinct phenotypic subpopulations of circulating cd4 cxcr5 follicular helper t cells in children with active IgA Vasculitis
BMC Immunology, 2016Co-Authors: Deying Liu, Jinghua Wang, Sirui Yang, Jinxiang Liu, Congcong Liu, Yanfang JiangAbstract:Circulating follicular helper T (Tfh) cells are a heterogeneous population of CD4+ helper T cells that promotes pathogenic immune responses in autoimmune diseases. In this study, we examined the status of different subpopulations of Tfh cells in peripheral circulation and their associations with various clinical characteristics of IgA Vasculitis (IgAV). According to the phenotypic expressions of different molecules, focus was given on six subpopulations of Tfh cells: CD4+CXCR5+, CD4+CXCR5+ICOS+, CD4+CXCR5+ICOS+PD-1+, CD4+CXCR5+ICOShighPD-1high, CD4+CXCR5+ICOS−PD-1+, and CXCR5+CD45RA−IL-21+. The frequencies of these six subpopulations and the circulating level of Tfh-related cytokine interleukin 21 (IL-21) were measured from 27 patients with IgAV and 15 healthy controls (HC) by flow cytometry and flow cytometric bead array, respectively. Significantly higher frequencies of CD4+CXCR5+, CD4+CXCR5+ICOS+, CD4+CXCR5+ICOS+PD-1+, CD4+CXCR5+ICOShighPD-1high and CXCR5+CD45RA−IL-21+ Tfh cells, as well as higher levels of plasma IL-21, were detected in IgAV patients compared to HC. The level of each Tfh subpopulation varied by the presenting symptoms of IgAV, but did not differ between patients treated or not treated with glucocorticoids. When the disease entered the remission stage following treatment, circulating levels of CD4+CXCR5+, CD4+CXCR5+ICOS+, CD4+CXCR5+ICOS+PD-1+, CD4+CXCR5+ICOShighPD-1high and CXCR5+CD45RA−IL-21+ Tfh cells, as well as plasma IL-21 levels were reduced. Among the six subpopulations of Tfh cells, both CD4+CXCR5+ICOS+ and CXCR5+CD45RA−IL-21+ significantly and positively correlated with serum IgA and plasma IL-21 levels, but only CXCR5+CD45RA−IL-21+ significantly and negatively correlated with the serum C4 level. Tfh cells may differentially contribute to the development of IgAV or predict disease progression. These findings provide novel insights in the pathogenesis of IgAV and may benefit treatment development targeting organ-specific presenting symptoms of IgAV.
Seza Ozen - One of the best experts on this subject based on the ideXlab platform.
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identification of a shared genetic risk locus for kawasaki disease and IgA Vasculitis by a cross phenotype meta analysis
Rheumatology, 2021Co-Authors: Elio G Carmona, Seza Ozen, Raquel Lopezmejias, Alojzija Hocevar, Jose A Garciagimenez, Chiea Chuen Khor, Jongkeuk Lee, Ekim Z Taskiran, Lili Liu, Mario GorenjakAbstract:Objectives Combination of genomic data of different pathologies as a single phenotype has emerged as a useful strategy to identify genetic risk loci shared among immune-mediated diseases. Our study aimed to increase our knowledge of the genetic contribution to Kawasaki disease (kDa) and IgA Vasculitis (IgAV) by performing the first comprehensive large-scale analysis on the genetic overlap between both pediatric Vasculitis. Methods A total of 1,190 Vasculitis patients and 11 302 healthy controls were analyzed. First, in the discovery phase, genome-wide data of 405 kDa patients and 6,252 controls and 215 IgAV patients and 1,324 controls, all of European origin, were combined using an inverse variance meta-analysis. Second, the top associated polymorphisms were selected for replication in additional independent cohorts (570 cases and 3,726 controls). Polymorphisms with p-values ≤ 5x1 0 -8 in the global IgAV-kDa meta-analysis were considered as shared genetic risk loci. Results A genetic variant, rs3743841, located in an intron of the NAGPA gene, reached genome-wide significance in the cross-disease meta-analysis (p= 8.06x10-10). Additionally, when IgAV was individually analyzed, a strong association between rs3743841 and this Vasculitis was also evident (p= 1.25x10-7; OR (95% CI)=1.47 (1.27-1.69)). In silico functional annotation showed that this polymorphism acts as a regulatory variant modulating the expression levels of the NAGPA and SEC14L5 genes. Conclusion We have identified a new risk locus with pleiotropic effects on the two Vasculitis of childhood analyzed. This locus represents the strongest non-HLA signal described for IgAV to date.
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predictive biomarkers of IgA Vasculitis with nephritis by metabolomic analysis
Seminars in Arthritis and Rheumatism, 2020Co-Authors: Selcan Demir, Erdal Sag, Ozan Kaplan, Mustafa Celebier, Yelda Bilginer, Incilay Lay, Seza OzenAbstract:Abstract Background IgA Vasculitis (IgAV) is the most common Vasculitis of childhood. Renal involvement defines late morbidity of the disease. A better understanding of the pathophysiology of the progression to kidney disease and predictive biomarkers are required for better management of IgAV and its nephritis (IgAVN). Objectives An untargeted metabolomics approach was performed to reveal the underlying molecular mechanism of disease pathogenesis and to define potential biomarkers from plasma samples from IgAV and IgAVN patients. Methods Forty-five active IgAV patients (H) and six healthy controls (C) were enrolled in the study. Plasma samples were collected on the same day of diagnosis and before any immunosuppressive treatment was initiated. At the time of diagnosis and sample collection, none of the patients had renal involvement. We used Quadrupole Time of Flight Mass Spectrometry (Q-TOF LC/MS) to investIgAte the alterations in plasma metabolomic profiles. Three separate pools were created: healthy controls (group C), active IgAV patients who did not develop renal involvement (group H), and patients who developed IgAVN at follow up (group N). Peak picking, grouping, and comparison parts were performed via XCMS ( https://xcmsonline.scripps.edu/ ) software. Results At follow-up, IgAVN developed in 6 out of 45 IgAV patients. The median time of renal involvement development is 23 days (range 5–45 days). Of these, 3 had nephritic proteinuria, one had nephrotic proteinuria, and 2 had microscopic hematuria. There were no significant differences in gender, age, clinical manifestations, and laboratory findings between the six patients who developed renal involvement and those who did not. In multivariate analysis, there was no significant association between any of the defined demographic and clinical characteristics (male sex, gastrointestinal system involvement, joint involvement, CRP, WBC, PLT) and the occurrence of renal involvement. Totally 2618 peaks were detected for group H, N, and C. Among them, 355 peaks were found to be statistically significant and reliable (p 1.5) between the groups C and H, and 66 peaks were found to be changed (fold change >1.5) between the groups H and N. The number of the peaks on the intersection of the peaks found to be different between the groups (C and H) and (H and N) was 39. Based on putative identification results, 15 putatively identified metabolites matched with 11 peaks were presented as biomarker candidates after careful evaluation with a clinical perspective. Conclusion We suggest that DHAP (18:0), prostaglandin D2/I2, porphobilinogen, 5-methyltetrahydrofolic acid, and N-Acetyl-4-O-acetylneuraminic acid/N-Acetyl-7-O-acetylneuraminic acid may serve as biomarkers for predicting kidney disease. Future studies with larger groups of IgAV patients are needed to validate the identified metabolic profile.
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sat0487 predictive biomarkers of i IgA Vasculitis with nephritis by metabolomic analysis
Annals of the Rheumatic Diseases, 2020Co-Authors: Selcan Demir, Erdal Sag, Ozan Kaplan, Mustafa Celebier, Yelda Bilginer, Seza OzenAbstract:Background: IgA Vasculitis/ Henoch Schonlein Purpura (IgAV/HSP) is the most common Vasculitis of childhood and renal involvement is the most serious long-term complication. A better understanding of the pathophysiology of the progression to kidney disease is required for better treatment to be achieved and current biomarkers of Ig A Vasculitis with nephritis (IgAVN) lack the predictive value. Objectives: In this study, an untargeted metabolomics approach was performed to reveal the underlying molecular mechanism of disease pathogenesis and to find potential biomarkers of plasma samples from patients with IgAV and IgAVN. Methods: IgAV/HSP was diagnosed according to the Ankara criteria in 2008 (1). Forty-five patients, including 39 active IgAV patients (H), 6 IgAVN (N), and 6 age- and gender-matched healthy controls (C), were enrolled in the study. Plasma samples from subjects were collected on the same day of IgAV(HSP) diagnosis and before steroid or other immunosuppressive treatment initiated. This study has utilized liquid chromatography-mass spectrometry (LC-MS/ Q-TOF) to investIgAte the alterations in plasma metabolomic profiles. Three separate pools, health controls, active IgAV, and IgAVN were created. Peak picking, grouping, and comparison parts were performed (metabolite profiling) via XCMS (https://xcmsonline.scripps.edu/) software. Results: Totally 2618 peaks were detected for group H, N and C. Among them 355 peaks were found to be statistically significant and reliable (p 1.5) between the groups C and H. On the other hand, 66 peaks were found to be changed (fold change >1.5) between the groups H and N. The number of the peaks on the intersection of the peaks found to be changed between the groups (C and H) and (H and N) was 39. This situation was illustrated in Figure 1. Based on putative identification results, 15 peaks were matched with 24 metabolites. The list of these metabolites is given in Table 1. Conclusion: Certain differences in metabolites were identified between controls and IgAV patients and between those with and without kidney involvement. References: [1]Ozen S, Pistorio A, Iusan SM, Bakkaloglu A, Herlin T, Brik R, et al. EULAR/PRINTO/PRES criteria for Henoch-Schonlein purpura, childhood polyarteritis nodosa, childhood Wegener granulomatosis and childhood Takayasu arteritis: Ankara 2008. Part II: final classification criteria. Ann Rheum Dis 2010;69(5):798e806. Disclosure of Interests: Selcan Demir: None declared, Mustafa Celebier: None declared, Ozan Kaplan: None declared, Erdal Sag Grant/research support from: Novartis and SOBI financially supported the HELIOS registry during the establishment of infrastructure, Yelda Bilginer Grant/research support from: Novartis and SOBI financially supported the HELIOS registry during the establishment of infrastructure, Seza Ozen Consultant of: Novartis, Pfizer, Speakers bureau: SOBI, Novartis
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IgA Vasculitis henoch schonlein purpura in children
Expert opinion on orphan drugs, 2017Co-Authors: Erdal Sag, Serap Z Arici, Seza OzenAbstract:ABSTRACTIntroduction: IgA Vasculitis/Henoch Schonlein Purpura (IgAV/HSP) is the most common childhood Vasculitis in most parts of the world. This is basically a self-limited disease, however the association of gastrointestinal and renal morbidity is well known.Areas covered: This review focuses on the classification of IgAV/HSP and management of specific organ involvements based on recent recommendations.Expert opinion: The new pediatric classification criteria allow pediatricians to pursue multicenter controlled studies for the unmet needs in the disease. Clinicians should be aware of the early morbidity associated with GI involvement and the late morbidity associated with renal involvement. Recurrences are possible. Treatment depends on the extent of clinical features and organ involvement.
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IgA Vasculitis henoch schonlein purpura polyarteritis nodosa granulomatous polyangiitis wegener granulomatosis and other vasculitides
Handbook of Systemic Autoimmune Diseases, 2016Co-Authors: Seza Ozen, Y BilginerAbstract:Abstract Vasculitides are the large spectrum of diseases due to the inflammation of the respective blood vessels. The vasculitic diseases tend to affect certain vessel sizes and hence have been classified according to the predominant vessel involvement. The vasculitides that we encounter in childhood will be the main focus of this chapter, except Kawasaki disease. Among these, IgA Vasculitis (IgAV) or Henoch–Schonlein purpura (HSP) is the most common childhood Vasculitis in most parts of the world. We will present the 2008 classification criteria for IgAV (HSP) and the other common vasculitides in childhood. We still lack high-evidence data for the management of IgAV (HSP). Polyarteritis nodosa may affect any organ system and thus its diagnosis and differential diagnosis continues to be a challenge to the pediatrician. Granulomatous polyangiitis or Wegener granulomatosis is the most common antineutrophil cytoplasmic antibody-associated Vasculitis we see in children. Recent adult studies suggest that rituximab is a promising alternative for these patients. Takayasu arteritis is a large vessel disease that also affects children and has a more insidious onset. Finally the more rare forms of Vasculitis that we see in children will be briefly reviewed.
