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BAFF, APRIL and BAFF-R are key proteins involved in the development of B-lymphocytes and autoimmunity. Additionally, BAFF, APRIL and BAFFR polymorphisms were associated with immune-mediated conditions, being BAFF GCTGT>A a shared insertion-deletion genetic variant for several autoimmune diseases. Accordingly, we assessed whether BAFF, APRIL and BAFFR represent novel genetic risk factors for Immunoglobulin-A vasculitis (IgAV), a predominantly B-lymphocyte inflammatory condition. BAFF rs374039502, which colocalizes with BAFF GCTGT>A, and two tag variants within APRIL (rs11552708 and rs6608) and BAFFR (rs7290134 and rs77874543) were genotyped in 386 Caucasian IgAV patients and 806 matched healthy controls. No genotypes or alleles differences were observed between IgAV patients and controls when BAFF, APRIL and BAFFR variants were analysed independently. Likewise, no statistically significant differences were found in the genotype and allele frequencies of BAFF, APRIL or BAFFR 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 APRIL and BAFFR haplotypes were compared between IgAV patients and controls and between IgAV patients stratified according to the clinical characteristics mentioned above. Our results suggest that BAFF, APRIL and BAFFR do not contribute to the genetic network underlying IgAV.

Objectives: Interferon regulatory factor 5 (IRF5) is a major regulator of type I interferon induction and is also critical to produce pro-inflammatory cytokines. An influence of IRF5 genetic variants on the increased risk of immune-mediated diseases has been described. Accordingly, we aimed to evaluate the implication of IRF5 in the pathogenesis of Immunoglobulin-A vasculitis (IgAV), an inflammatory vascular pathology., Methods: Three tag genetic variants (rs2004640, rs2070197 and rs10954213), representative of 3 different haplotype blocks within IRF5, were genotyped in 372 Caucasian patients with IgAV and 876 sex and ethnically matched healthy controls by TaqMan assays., Results: No significant differences in the genotype and allele frequencies between patients with IgAV and healthy controls were observed when each IRF5 polymorphism was evaluated independently. Likewise, no significant differences between patients with IgAV and healthy controls were found when we assessed the three IRF5 polymorphisms combined, conforming haplotypes. In addition, there were no significant differences in genotype, allele and haplotype frequencies of IRF5 when patients with IgAV were stratified according to the age at disease onset or to the presence/absence of gastrointestinal or renal manifestations., Conclusions: Our results do not support an influence of IRF5 on the pathogenesis of IgAV.

Diana Prieto-Peña,1 Santos Castañeda,2,3 Belén Atienza-Mateo,1 Ricardo Blanco,1 Miguel Ángel González-Gay1,4,5 1Department of Rheumatology, Research Group on Genetic Epidemiology and Atherosclerosis in Systemic Diseases and in Metabolic Bone Diseases of the Musculoskeletal System, IDIVAL, Hospital Universitario Marqués de Valdecilla, Santander, Spain; 2Department of Rheumatology, H. Universitario de La Princesa, IIS-Princesa, Madrid, Spain; 3Cátedra UAM-ROCHE, EPID-Future, Universidad Autónoma Madrid (UAM), Madrid, Spain; 4School of Medicine, Universidad de Cantabria, Santander, Spain; 5Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South AfricaCorrespondence: Miguel Ángel González-GayDepartment of Rheumatology, Research Group on Genetic Epidemiology and Atherosclerosis in Systemic Diseases and in Metabolic Bone Diseases of the Musculoskeletal System, IDIVAL, Hospital Universitario Marqués de Valdecilla, Avenida Valdecilla s/n, Santander, 39008, SpainEmail miguelaggay@hotmail.comAbstract: Giant cell arteritis (GCA) is characterized by granulomatous inflammation of large and medium-sized vessels. It is the most common vasculitis among elderly people in Europe and North America. GCA usually presents with ischemic cranial manifestations such as headache, scalp tenderness, visual manifestations, and claudication of the tongue and jaw. Thickness and tenderness of temporal arteries are the most recognizable signs of GCA on physical examination. Laboratory tests usually show raised acute phase reactants. Skin manifestations are uncommon in GCA and are rarely found as a presenting symptom of GCA. Necrosis of the scalp and tongue is the most common ischemic cutaneous manifestation of GCA. Although infrequent, when present it reflects severe affection and poor prognosis of GCA. Panniculitis-like lesions have been reported in the setting of GCA, with nodules being the most common finding. Other entities, such as generalized granuloma annulare or basal cell carcinoma have been occasionally described in GCA patients. Prompt recognition and initiation of therapy are crucial to prevent serious complications of GCA. When high suspicion of GCA exists, immediate administration of glucocorticoids is recommended. It is advisable to refer the patient to a specialist GCA team for further multidisciplinary assessment.Keywords: giant cell arteritis, cutaneous manifestations, skin, vasculitis