HLA-G 14-bp polymorphism: a possible marker of systemic treatment response in psoriasis vulgaris? Preliminary results of a retrospective study

Abstract

Human leukocyte antigen-G (HLA-G) is a nonclassical HLA class I molecule that exerts an immunosuppressive function. A 14-base pair (bp) sequence insertion/deletion (INS/DEL) polymorphism in the exon 8 at the 3' untranslated region (UTR) modifies mRNA stability and protein production and has been shown to concur with efficacy of pharmacological treatments in immune-mediated conditions. The aim of this study was to assess for the first time the correlation between HLA-G 14-bp INS/DEL polymorphism with the response to systemic therapy in psoriatic patients. We retrospectively analyzed the HLA-G 14-bp INS/DEL polymorphism of HLA-G gene in patients with moderate to severe plaque psoriasis: 21 treated with acitretin, 16 with cyclosporine, 11 with anti-TNF-α. Patients who reached PASI 75 at weeks 10-16 were considered responders. Among patients treated with acitretin, we observed a significantly increased frequency of the HLA-G DEL allele and of the DEL/DEL genotype in responder patients when compared with nonresponders. An association between HLA-G genotype and response to cyclosporine and biologics was not found. The significant association between HLA-G 14-bp DEL allele and 14-bp DEL/DEL genotype and acitretin clinical outcome may suggest an advantage of this allele and propose this HLA-G polymorphism as a potential marker of response to acitretin in psoriatic patients.

Recent Advances in Our Understanding of HLA-G Biology: Lessons from a Wide Spectrum of Human Diseases

“…Borghi et al have analyzed the correlation between HLA-G 14-bp ins/del polymorphism and the response of psoriatic patients to systemic therapy (acitretin, cyclosporine, or anti-TNF- α ). They found an increased frequency of HLA-G del allele and del/del genotype in responders only among patients treated with acitretin, and they proposed this HLA-G polymorphism as a potential marker of response to acitretin in psoriatic patients [ 69 ]. In contrast, Naidoo et al have analyzed the relationship between HLA-G and statins treatment in patients with asthma.…”

HLA-G Molecules in Autoimmune Diseases and Infections

“…Psoriasis management can be divided into three main types: topical drugs, light therapy, and systemic medications. Evaluation of therapeutic effects on sHLA-G expression has shown an increase in plasmatic levels of systemic treated patients (efalizumab, cyclosporin A, and acitretin) ( 88 ) and a significant association between HLA-G 14bp DEL allele and 14bp DEL/DEL genotype with acitretin clinical outcome ( 89 ). We can suppose a possible direct effect of HLA-G in antagonizing systemic T helper 1 activation and with a potential role as a marker of response to acitretin in psoriatic patients.…”

Human leukocyte antigen‐G polymorphism influences the age of onset and autoantibody status in rheumatoid arthritis

“…Although HLA‐G is less polymorphic in the coding region, high degree of variation is observed in the 5′‐upstream regulatory region (URR) and 3′‐untranslated region (UTR) regions involved in transcriptional and post‐transcriptional regulation of HLA‐G. The 14 bp insertion (Ins)/deletion (Del), +3142 G>C, +3187 G>A polymorphisms have been implicated in various autoimmune diseases like RA, Juvenile idiopathic arthritis (JIA), Systemic lupus erythematosus (SLE), psoriasis and multiple sclerosis . The 14 bp Ins is reported to be associated with reduced gene expression .…”