Lolli, SerenaGiambra, VincenzoCianci, RossellaMattioli, ClaudiaTampella, GiacomoCattalini, MarcoPandolfi, FrancoPlebani, AlessandroFrezza, Domenico2021-12-132021-12-132009-12-15Giambra, V. vd. (2009). "Allele *1 of HS1.2 enhancer associates with selective IgA deficiency and IgM concentration". Journal of Immunology, 183(12), 8280-8285.0022-1767https://doi.org/10.4049/jimmunol.0902426https://www.jimmunol.org/content/183/12/8280http://hdl.handle.net/11452/23187Selective IgA deficiency (IGAD) is the most common primary immunodeficiency, yet its pathogenesis is elusive. The IG (heavy) H chain human 3' Regulatory Region harbors three enhancers and has an important role In Ig synthesis. HS1.2 is the only polymorphic enhancer of the 3'RRs. We therefore evaluated HS1.2 allelic frequencies in 88 IGAD patients and 101 controls. Our data show that IGAD patients have a highly significant increase of homozygousity of the allele *1 (39% in the IGAD patients and 15% in controls), with an increase of 2.6-fold. Allele *4 has a similar trend of allele *2, both showing a significant decrease of frequency in IGAD. No relationship was observed between allele *1 frequencies and serum levels of IgG. However, allele *1 was associated in IGAD patients with relatively low lgM levels (within the 30th lowest percentile of patients). The HS1.2 polymorphism influences Ig seric production, but not IgG switch, in fact 30th lowest or highest percentile of IgG in patients did not associate to different frequencies of HS1.2 alleles. The control on normal healthy subjects did not correlate high or low levels of IgM or IgG with HS1.2 allelic frequence variation. Overall our candidate gene approach confirms that the study of polymorphisms in human diseases is a valid tool to investigate the function of these Regulatory Regions that confers multiple immune features.eninfo:eu-repo/semantics/openAccessCommon variable immunodeficiencyVirtually identical enhancersHeavy-chain locusB-cellsRegulatory regionHistone modificationsIncreased frequencyHs1,2 enhancerCeliac-diseaseImmunoglobulinImmunology3' flanking regionAdolescentAllelesBase sequenceChildChild, preschoolEnhancer elements, geneticFemaleGene frequencyHumansIgA deficiencyImmunoglobulin GImmunoglobulin heavy chainsImmunoglobulin MImmunoglobulin switch regionMaleMolecular sequence dataRegulatory sequences, nucleic acidYoung adultArticle0002728613000732-s2.0-76249103100828082851831220007591ImmunologyImmunoglobulin Heavy Chains; Regulatory Sequences; AICDA (Activation-induced Cytidine Deaminase)Immunoglobulin AImmunoglobulin GImmunoglobulin heavy chainImmunoglobulin MAdultAlleleArticleDNA polymorphismEnhancer regionFemaleGene frequencyGenetic variabilityHomozygosityHumanImmunoglobulin A deficiencyImmunoglobulin blood levelImmunoglobulin productionMajor clinical studyMalePathogenesisPriority journalAdolescentAlleleBloodChildComparative studyDNA flanking regionGeneticsImmunoglobulin geneImmunologyMolecular geneticsNucleotide sequencePreschool childRegulatory sequence