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.

An early and accurate diagnosis of connective tissue diseases-related interstitial lung disease (CTD-ILD) is crucial for delaying lung fibrosis, but its unknown etiology and the limitations of clinical tools make it challenging for clinicians. PDGF and TGFB are the main profibrotic genes. We evaluated PDGFA, TGFB1, TGFB2, and TGFB3 role in the diagnosis of ILD associated with rheumatoid arthritis (RA), systemic sclerosis (SSc), and inflammatory myopathies (IM). Blood was collected from 289 patients:33 RA-ILD, 31 SSc-ILD, 29 IM-ILD; and 22 RA-nonILD, 18 SSc-nonILD, 8 IM-nonILD; and 148 idiopathic pulmonary fibrosis (IPF). The relative expression was quantified by qPCR. Lower PDGFA, TGFB1, and TGFB2 expression differentiated RA-ILD from RA-nonILD patients, acting as ILD early diagnostic biomarkers in RA with cut-offs of <0.01153, <0.3185, and <0.001410, respectively. SSc-ILD patients revealed decreased TGFB2 expression compared to SSc-nonILD patients, with a cut-off of 0.0166 and >0.001547, respectively. PDGFA and TGFB2, as well as TGFB2 and TGFB3 expression were associated with RA-ILD and SSc-ILD prognosis, respectively. PDGFA and TGFB are promising blood biomarkers with clinical value for the early and accurate CTD-ILD diagnosis.