Mucosal Immune Defence Gene Polymorphisms as Relevant Players in the Pathogenesis of IgA Vasculitis?

This research was funded by European Union FEDER funds and “Fondo de Investigaciones Sanitarias” from “Instituto de Salud Carlos III” (ISCIII, Health Ministry, Spain), grant numbers PI18/00042 and PI21/00042. J.C.B.-L. is a recipient of a PFIS program fellowship from the ISCIII, co-funded by the European Social Fund (‘Investing in your future’), grant number FI22/00020. M.S.M.-G. is supported by funds of “Fondo de Investigaciones Sanitarias” from ISCIII, grant number PI121/00042. R.L.-M. is a recipient of a Miguel Servet type II program fellowship from the ISCIII, co-funded by ESF (“Investing in your future”), grant number CPII21/00004.ITGAM–ITGAX (rs11150612, rs11574637), VAV3 rs17019602, CARD9 rs4077515, DEFA (rs2738048, rs10086568), and HORMAD2 rs2412971 are mucosal immune defence polymorphisms, that have an impact on IgA production, described as risk loci for IgA nephropathy (IgAN). Since IgAN and Immunoglobulin-A vasculitis (IgAV) share molecular mechanisms, with the aberrant deposit of IgA1 being the main pathophysiologic feature of both entities, we assessed the potential influence of the seven abovementioned polymorphisms on IgAV pathogenesis. These seven variants were genotyped in 381 Caucasian IgAV patients and 997 matched healthy controls. No statistically significant differences were observed in the genotype and allele frequencies of these seven polymorphisms when the whole cohort of IgAV patients and those with nephritis were compared to controls. Similar genotype and allele frequencies of all polymorphisms were disclosed when IgAV patients were stratified according to the age at disease onset or the presence/absence of gastrointestinal or renal manifestations. Likewise, no ITGAM–ITGAX and DEFA haplotype differences were observed when the whole cohort of IgAV patients, along with those with nephritis and controls, as well as IgAV patients, stratified according to the abovementioned clinical characteristics, were compared. Our results suggest that mucosal immune defence polymorphisms do not represent novel genetic risk factors for IgAV pathogenesis.European Commission ECInstituto de Salud Carlos III ISCIIIEuropean Social Fund CPII21/00004, FI22/00020, PI121/00042 ESFConsejería de Salud y Familias, Junta de Andalucía PI18/00042, PI21/0004

IgA Vasculitis: Influence of CD40, BLK and BANK1 Gene Polymorphisms

CD40, BLK and BANK1 genes involved in the development and signaling of B-cells are identified as susceptibility loci for numerous inflammatory diseases. Accordingly, we assessed the potential influence of CD40, BLK and BANK1 on the pathogenesis of immunoglobulin-A vasculitis (IgAV), predominantly a B-lymphocyte inflammatory condition. Three genetic variants within CD40 (rs1883832, rs1535045, rs4813003) and BLK (rs2254546, rs2736340, rs2618476) as well as two BANK1 polymorphisms (rs10516487, rs3733197), previously associated with inflammatory diseases, were genotyped in 382 Caucasian patients with IgAV and 955 sex- and ethnically matched healthy controls. No statistically significant differences were observed in the genotype and allele frequencies of CD40, BLK and BANK1 when IgAV patients and healthy controls were compared. Similar results were found when CD40, BLK and BANK1 genotypes or alleles frequencies were compared between patients with IgAV stratified according to the age at disease onset or to the presence/absence of gastrointestinal or renal manifestations. Moreover, no CD40, BLK and BANK1 haplotype differences were disclosed between patients with IgAV and healthy controls and between patients with IgAV stratified according to the clinical characteristics mentioned above. Our findings indicate that CD40, BLK and BANK1 do not contribute to the genetic background of IgAV.European CommissionInstituto de Salud Carlos III" (ISCIII, Health Ministry, Spain) PI18/00042 PI21/00042 Instituto de Salud Carlos IIIEuropean Social Fund (ESF) CM20/00006RICORS Program from ISCIIIEuropean Commission RD21/0002/0025RETICS Program (ISCIII) RD16/0012/0009RETICS Program (European Regional Development Fund (ERDF) RD16/0012/0009European Union FEDER fund RD16/0012/0014 PI17/00409Research Executive Agency (REA) of the European Union 734899Miguel Servet type II program fellowship from the ISCIIIESF ("Investing in your future") CPII21/0000

El laboratorio en la vigilancia, el control y la investigación de la rabia en España. La experiencia del Centro Nacional de Microbiología

España presenta una situación peculiar Europa, ya que nunca se vio afectada por la epizootia europea de rabia vulpina, pero mantiene un tráfico intenso de bienes y personas con territorios altamente endémicos del norte de África, e incluso fronteras terrestres enCeuta y Melilla, lo que nos coloca en una situación vulnerable en cuanto a importación de casos. Por otra parte, sabemos de la presencia de dos de los lisavirus de murciélago europeos en nuestro territorio. El laboratorio es un elemento esencial en la vigilancia que se hace imprescindible ante esta situación. El Centro Nacional de Microbiología lleva más de treinta años actuando de laboratorio nacional de referencia en apoyo de los laboratorios autonómicos existentes y haciendo diagnóstico para el resto del territorio, además de representar a España en la red europea de laboratorios RABNET. Así, en el CNM se han diagnosticado y caracterizado la gran mayoría de los casos declarados en España en este período, tanto de rabia de murciélagos, como de rabia importada animal y humana. De manera complementaria a esta actividad de vigilancia, se realizan investigaciones tanto sobre rabia canina como de murciélagos, que, desde hace años, se han ampliado a otros agentes víricos asociados a murciélagosSpain shows peculiarities regarding rabies in Europe. It was not affected by the European vulpine epizootic but keeps an intense traffic of goods and people with highly endemic territories in North Africa and even has terrestrial boundaries in the cities of Ceuta and Melilla. This makes Spain particularly vulnerable to importation of rabies cases. On the other hand,we know the presence in Spain of two of the five bat lyssaviruses endemic from Europe. The laboratory is an essential tool for the surveillance that is strictly necessary to keep in order to handle this situation. The National Center of Microbiology (CNM)provides support to autonomic laboratories, makes primary diagnosis for the rest of the territory and represents Spain in the European laboratory net RABNET from more than thirty years to now, according to its role of National Reference Laboratory. Duringthis period, the CNM has diagnosed and characterized most rabies cases declared in Spain, including both bat rabies and imported animal and human cases. Associated to these surveillance activities, the CNM makes research in the field of canine and bat rabies, which has been extended to other bat-associated viruses in the last years

IgA vasculitis: influence of CD40, BLK and BANK1 gene polymorphisms

CD40, BLK and BANK1 genes involved in the development and signaling of B-cells are identified as susceptibility loci for numerous inflammatory diseases. Accordingly, we assessed the potential influence of CD40, BLK and BANK1 on the pathogenesis of immunoglobulin-A vasculitis (IgAV), predominantly a B-lymphocyte inflammatory condition. Three genetic variants within CD40 (rs1883832, rs1535045, rs4813003) and BLK (rs2254546, rs2736340, rs2618476) as well as two BANK1 polymorphisms (rs10516487, rs3733197), previously associated with inflammatory diseases, were genotyped in 382 Caucasian patients with IgAV and 955 sex- and ethnically matched healthy controls. No statistically significant differences were observed in the genotype and allele frequencies of CD40, BLK and BANK1 when IgAV patients and healthy controls were compared. Similar results were found when CD40, BLK and BANK1 genotypes or alleles frequencies were compared between patients with IgAV stratified according to the age at disease onset or to the presence/absence of gastrointestinal or renal manifestations. Moreover, no CD40, BLK and BANK1 haplotype differences were disclosed between patients with IgAV and healthy controls and between patients with IgAV stratified according to the clinical characteristics mentioned above. Our findings indicate that CD40, BLK and BANK1 do not contribute to the genetic background of IgAV.Funding: This study was supported by European Union FEDER funds and “Fondo de Investigaciones Sanitarias” (grants PI18/00042 and PI21/00042) from “Instituto de Salud Carlos III” (ISCIII, Health Ministry, Spain). D.P.-P. is a recipient of a Río Hortega program fellowship from the ISCIII, co-funded by the European Social Fund (ESF, “Investing in your future”) (grant number CM20/00006). F.G. is supported by funds of the RICORS Program from ISCIII, co-funded by the European Union (grant number RD21/0002/0025). V.P.-C. is supported by funds of PI18/00042. S.R.-M. is supported by funds of the RETICS Program (RD16/0012/0009) (ISCIII, co-funded by the European Regional Development Fund (ERDF)). O.G. is a staff member of Xunta de Galicia (Servizo Galego de Saude (SERGAS)) through a research-staff stabilization contract (ISCIII/SERGAS) and his work is funded by ISCIII and the European Union FEDER fund (grant numbers RD16/0012/0014 (RIER) and PI17/00409). He is a beneficiary of project funds from the Research Executive Agency (REA) of the European Union in the framework of MSCA-RISE Action of the H2020 Program, project 734899—Olive-Net. R.L.-M. is a recipient of a Miguel Servet type II program fellowship from the ISCIII, co-funded by ESF (“Investing in your future”) (grant number CPII21/00004). Acknowledgments: We are indebted to the patients and healthy controls for their essential collaboration on this study. We also thank the National DNA Bank Repository (Salamanca) for supplying part of the control samples

Mucosal Immune Defence Gene Polymorphisms as Relevant Players in the Pathogenesis of IgA Vasculitis?

ITGAM–ITGAX (rs11150612, rs11574637), VAV3 rs17019602, CARD9 rs4077515, DEFA (rs2738048, rs10086568), and HORMAD2 rs2412971 are mucosal immune defence polymorphisms, that have an impact on IgA production, described as risk loci for IgA nephropathy (IgAN). Since IgAN and Immunoglobulin-A vasculitis (IgAV) share molecular mechanisms, with the aberrant deposit of IgA1 being the main pathophysiologic feature of both entities, we assessed the potential influence of the seven abovementioned polymorphisms on IgAV pathogenesis. These seven variants were genotyped in 381 Caucasian IgAV patients and 997 matched healthy controls. No statistically significant differences were observed in the genotype and allele frequencies of these seven polymorphisms when the whole cohort of IgAV patients and those with nephritis were compared to controls. Similar genotype and allele frequencies of all polymorphisms were disclosed when IgAV patients were stratified according to the age at disease onset or the presence/absence of gastrointestinal or renal manifestations. Likewise, no ITGAM–ITGAX and DEFA haplotype differences were observed when the whole cohort of IgAV patients, along with those with nephritis and controls, as well as IgAV patients, stratified according to the abovementioned clinical characteristics, were compared. Our results suggest that mucosal immune defence polymorphisms do not represent novel genetic risk factors for IgAV pathogenesis

IgA Vasculitis: Influence of CD40, BLK and BANK1 Gene Polymorphisms

CD40, BLK and BANK1 genes involved in the development and signaling of B-cells are identified as susceptibility loci for numerous inflammatory diseases. Accordingly, we assessed the potential influence of CD40, BLK and BANK1 on the pathogenesis of immunoglobulin-A vasculitis (IgAV), predominantly a B-lymphocyte inflammatory condition. Three genetic variants within CD40 (rs1883832, rs1535045, rs4813003) and BLK (rs2254546, rs2736340, rs2618476) as well as two BANK1 polymorphisms (rs10516487, rs3733197), previously associated with inflammatory diseases, were genotyped in 382 Caucasian patients with IgAV and 955 sex- and ethnically matched healthy controls. No statistically significant differences were observed in the genotype and allele frequencies of CD40, BLK and BANK1 when IgAV patients and healthy controls were compared. Similar results were found when CD40, BLK and BANK1 genotypes or alleles frequencies were compared between patients with IgAV stratified according to the age at disease onset or to the presence/absence of gastrointestinal or renal manifestations. Moreover, no CD40, BLK and BANK1 haplotype differences were disclosed between patients with IgAV and healthy controls and between patients with IgAV stratified according to the clinical characteristics mentioned above. Our findings indicate that CD40, BLK and BANK1 do not contribute to the genetic background of IgAV

Mucosal immune defence gene polymorphisms as relevant players in the pathogenesis of IgA vasculitis?

ITGAM-ITGAX (rs11150612, rs11574637), VAV3 rs17019602, CARD9 rs4077515, DEFA (rs2738048, rs10086568), and HORMAD2 rs2412971 are mucosal immune defence polymorphisms, that have an impact on IgA production, described as risk loci for IgA nephropathy (IgAN). Since IgAN and Immunoglobulin-A vasculitis (IgAV) share molecular mechanisms, with the aberrant deposit of IgA1 being the main pathophysiologic feature of both entities, we assessed the potential influence of the seven abovementioned polymorphisms on IgAV pathogenesis. These seven variants were genotyped in 381 Caucasian IgAV patients and 997 matched healthy controls. No statistically significant differences were observed in the genotype and allele frequencies of these seven polymorphisms when the whole cohort of IgAV patients and those with nephritis were compared to controls. Similar genotype and allele frequencies of all polymorphisms were disclosed when IgAV patients were stratified according to the age at disease onset or the presence/absence of gastrointestinal or renal manifestations. Likewise, no ITGAM-ITGAX and DEFA haplotype differences were observed when the whole cohort of IgAV patients, along with those with nephritis and controls, as well as IgAV patients, stratified according to the abovementioned clinical characteristics, were compared. Our results suggest that mucosal immune defence polymorphisms do not represent novel genetic risk factors for IgAV pathogenesis.Funding: This research was funded by European Union FEDER funds and “Fondo de Investigaciones Sanitarias” from “Instituto de Salud Carlos III” (ISCIII, Health Ministry, Spain), grant numbers PI18/00042 and PI21/00042. J.C.B.-L. is a recipient of a PFIS program fellowship from the ISCIII, co-funded by the European Social Fund (‘Investing in your future’), grant number FI22/00020. M.S.M.-G. is supported by funds of “Fondo de Investigaciones Sanitarias” from ISCIII, grant number PI121/00042. R.L.-M. is a recipient of a Miguel Servet type II program fellowship from the ISCIII, co-funded by ESF (“Investing in your future”), grant number CPII21/00004. Acknowledgments: We wish to thank all the subjects for their essential collaboration in this study. We also thank the National DNA Bank Repository (Salamanca) for supplying the control samples