New susceptible locus, rs9428555, is associated with pediatric-onset immunoglobulin A nephropathy and immunoglobulin A vasculitis in Koreans

Background:Interferon signaling pathway plays a relevant role in autoimmunity. Genetic variants in theinterferon regulatory factor (IRF) 5gene, that encodes the major regulator of the type I interferon induction [1], have been related to the development of several inflammatory diseases [2].Objectives:To determine the influence ofIRF5on Immunoglobulin-A vasculitis (IgAV), an inflammatory vascular disease.Methods:ThreeIRF5polymorphisms (rs2004640, rs2070197 and rs10954213) representative of 3 different haplotype blocks were genotyped in 372 Caucasian patients with IgAV and 876 sex and ethnically matched healthy controls.Results:No statistically significant differences between patients with IgAV and controls were observed when eachIRF5polymorphism was analyzed independently. Similarly, no statistically significant differences between patients with IgAV and controls were found whenIRF5polymorphisms were evaluated combined conforming haplotypes. Additionally, there were no statistically significant differences in genotype, allele and haplotype frequencies ofIRF5when patients with IgAV were stratified according to the age at disease onset or to the presence/absence of gastrointestinal or renal manifestations.Conclusion:Our results do not support an influence ofIRF5on the pathogenesis of IgAV.References:[1]Nat Immunol 2011; 12: 231-8;[2]Arthritis Res Ther 2014; 16: R146.Acknowledgments:This study was supported by European Union FEDER funds and “Fondo de Investigaciones Sanitarias” (grant PI18/00042) from ‘Instituto de Salud Carlos III’ (ISCIII, Health Ministry, Spain). RL-M is a recipient of a Miguel Servet type I programme fellowship from the ISCIII, co-funded by the European Social Fund (ESF, `Investing in your future´) (grant CP16/00033). SR-M is supported by funds of the RETICS Program (RD16/0012/0009) (ISCIII, co-funded by the European Regional Development Fund (ERDF)). VP-C is supported by a pre-doctoral grant from IDIVAL (PREVAL 18/01). LL-G is supported by funds of PI18/00042 (ISCIII, co-funded by ERDF).Disclosure of Interests:Sara Remuzgo Martinez: None declared, Fernanda Genre: None declared, Verónica Pulito-Cueto: None declared, D. Prieto-Peña: None declared, Belén Atienza-Mateo: None declared, Belén Sevilla: None declared, Javier Llorca: None declared, Norberto Ortego: None declared, Leticia Lera-Gómez: None declared, Maite Leonardo: None declared, Ana Peñalba: None declared, María Jesús Cabero: None declared, Luis Martín-Penagos: None declared, Jose Alberto Miranda-Filloy: None declared, Antonio Navas Parejo: None declared, Javier Sanchez Perez: None declared, Maximiliano Aragües: None declared, Esteban Rubio: None declared, MANUEL LEON LUQUE: None declared, Juan María Blanco-Madrigal: None declared, E. Galindez: None declared, Javier Martin Ibanez: None declared, Santos Castañeda: None declared, Ricardo Blanco Grant/research support from: Abbvie, MSD and Roche, Consultant of: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen and MSD, Speakers bureau: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen, Lilly and MSD, Miguel A González-Gay Grant/research support from: Pfizer, Abbvie, MSD, Speakers bureau: Pfizer, Abbvie, MSD, Raquel López-Mejías: None declared

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Non-visible haematuria in a military setting

Journal of The Royal Naval Medical Service ◽

10.1136/jrnms-104-177 ◽

2018 ◽

Vol 104 (3) ◽

pp. 177-182

Author(s):

D O’Brien ◽

K Houlberg

Keyword(s):

Basement Membrane ◽

Immunoglobulin A ◽

Armed Forces ◽

Common Finding ◽

Immunoglobulin A Nephropathy ◽

Hereditary Nephritis ◽

Military Recruits ◽

Thin Basement Membrane Disease ◽

Medical Examinations

AbstractAsymptomatic non-visible haematuria is a common finding at routine military medical examinations. This article briefly reviews the possible causes, which include malignancy, structural causes, exertion haematuria, hereditary nephritis, thin basement membrane disease (TBMD), immunoglobulin A nephropathy (IgAN), tuberculosis (TB) and schistosomiasis. This paper discusses how these conditions may affect potential military recruits as well as currently serving members of the Armed Forces, and offers a general approach to the management of a patient with non-visible haematuria.

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Role of the IL33 and IL1RL1 pathway in the pathogenesis of Immunoglobulin A vasculitis

Scientific Reports ◽

10.1038/s41598-021-95762-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Diana Prieto-Peña ◽

Sara Remuzgo-Martínez ◽

Fernanda Genre ◽

Verónica Pulito-Cueto ◽

Belén Atienza-Mateo ◽

...

Keyword(s):

Inflammatory Diseases ◽

Disease Onset ◽

Immunoglobulin A ◽

Genetic Network ◽

Signalling Pathway ◽

Immune Mediated ◽

Increased Risk ◽

Genotype And Allele Frequencies ◽

Immunoglobulin A Vasculitis

AbstractCytokines signalling pathway genes are crucial factors of the genetic network underlying the pathogenesis of Immunoglobulin-A vasculitis (IgAV), an inflammatory vascular condition. An influence of the interleukin (IL)33- IL1 receptor like (IL1RL)1 signalling pathway on the increased risk of several immune-mediated diseases has been described. Accordingly, we assessed whether the IL33-IL1RL1 pathway represents a novel genetic risk factor for IgAV. Three tag polymorphisms within IL33 (rs3939286, rs7025417 and rs7044343) and three within IL1RL1 (rs2310173, rs13015714 and rs2058660), that also were previously associated with several inflammatory diseases, were genotyped in 380 Caucasian IgAV patients and 845 matched healthy controls. No genotypes or alleles differences were observed between IgAV patients and controls when IL33 and IL1RL1 variants were analysed independently. Likewise, no statistically significant differences were found in IL33 or IL1RL1 genotype and allele frequencies when IgAV patients were stratified according to the age at disease onset or to the presence/absence of gastrointestinal (GI) or renal manifestations. Similar results were disclosed when IL33 and IL1RL1 haplotypes were compared between IgAV patients and controls and between IgAV patients stratified according to the clinical characteristics mentioned above. Our results suggest that the IL33-IL1RL1 signalling pathway does not contribute to the genetic network underlying IgAV.

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Analysis of the association between kidney injury biomarkers concentration and nephritis in immunoglobulin A vasculitis: A pediatric cohort study

International Journal of Rheumatic Diseases ◽

10.1111/1756-185x.13904 ◽

2020 ◽

Vol 23 (9) ◽

pp. 1184-1193

Author(s):

Katarzyna Dyga ◽

Edyta Machura ◽

Elżbieta Świętochowska ◽

Maria Szczepańska

Keyword(s):

Cohort Study ◽

Immunoglobulin A ◽

Kidney Injury ◽

Immunoglobulin A Vasculitis

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Immunoglobulin A Nephropathy in Blacks and Homozygosity for the Genetic Marker A2m

Annals of Internal Medicine ◽

10.7326/0003-4819-104-2-287_2 ◽

1986 ◽

Vol 104 (2) ◽

pp. 287 ◽

Cited By ~ 8

Author(s):

KOTRESHA NEELAKANTAPPA

Keyword(s):

Genetic Marker ◽

Immunoglobulin A ◽

Immunoglobulin A Nephropathy

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Podocytopathy in the mesangial proliferative immunoglobulin A nephropathy: new insights into the mechanisms of damage and progression

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfy413 ◽

2019 ◽

Vol 34 (8) ◽

pp. 1280-1285 ◽

Cited By ~ 9

Author(s):

Hernán Trimarchi ◽

Rosanna Coppo

Keyword(s):

Mesangial Cells ◽

Immunosuppressive Treatment ◽

Immunoglobulin A ◽

Primary Site ◽

New Drugs ◽

Immunoglobulin A Nephropathy ◽

Inflammatory Reactions ◽

Persistent Proteinuria ◽

Mesangial Area ◽

Function Loss

Abstract Immunoglobulin A nephropathy (IgAN) was defined as a mesangiopathic disease, since the primary site of deposition of IgA immune material is the mesangium, and proliferation of mesangial cells and matrix excess deposition are the first histopathologic lesions. However, the relentless silent progression of IgAN is mostly due to the development of persistent proteinuria, and recent studies indicate that a major role is played by previous damage of function and anatomy of podocytes. In IgAN, the podocytopathic changes are the consequence of initial alterations in the mesangial area with accumulation of IgA containing immune material. Podocytes are therefore affected by interactions of messages originally driven from the mesangium. After continuous insult, podocytes detach from the glomerular basement membrane. This podocytopathy favours not only the development of glomerular focal and segmental sclerosis, but also the progressive renal function loss. It is still debated whether these lesions can be prevented or cured by corticosteroid/immunosuppressive treatment. We aimed to review recent data on the mechanisms implicated in the podocytopathy present in IgAN, showing new molecular risk factors for progression of this disease. Moreover, these observations may indicate that the target for new drugs is not only focused on decreasing the activity of mesangial cells and inflammatory reactions in IgAN, but also on improving podocyte function and survival.

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