Impact of Single Nucleotide Polymorphisms of the Promoter of the TNF Gene on Adalimumab Treatment Responses in Hidradenitis Suppurativa.

BACKGROUND: Results of randomized clinical trials show great variation in response to treatment with adalimumab (ADA) in hidradenitis suppurativa (HS). This varied response may be associated with genetic polymorphisms. OBJECTIVES: The aim of the study was to study the association between carriage of single nucleotide polymorphisms (SNPs) in the promoter of the tumor necrosis factor (TNF) gene and their response to ADA. METHODS: Patients with moderate to severe HS who received ADA treatment for at least 12 weeks were enrolled. SNPs were analyzed with PCR-restriction fragment length polymorphism. Hidradenitis Suppurativa Clinical Response (HiSCR) score, International Hidradenitis Suppurativa Severity Scoring System 4 (IHS4) score, inflammatory lesion (AN) count, and draining tunnel (dT) count were collected at weeks 0, 12, 24, 36, and 48. RESULTS: HiSCR response after 12 weeks of ADA treatment was 71.8% among carriers of the common GGG haplotype and 50.0% among carriers of minor frequency SNP haplotypes (p: 0.031; odds ratio: 0.39). This significant difference persisted until week 36. Carriers of minor frequency SNP haplotypes also had a lower relative decrease of the AN count at weeks 12 and 24; the dT count and IHS4 were not statistically different between the two groups. CONCLUSIONS: Carriage of at least one minor frequency SNP haplotype of the promoter of the TNF gene is associated with a decreased response to ADA. This association may have an impact on treatment decision-making.

Association of NFKB1 -94ATTG ins/del polymorphism (rs28362491) with pemphigus vulgaris.

Pemphigus vulgaris is a rare chronic blistering skin disease resulting from IgG autoantibodies directed against transmembrane desmosomal glycoprotein desmoglein 3 and is the most common form of pemphigus. Since interleukin-1 receptor-associated kinase (IRAK-1)/nuclear factor-kappa B (NF-kappa B) pathway plays an essential role in the pathogenesis of autoimmune diseases, the aim of the present study was to explore the role of polymorphisms in three genes, named IRAK1 (rs3027898), NFKBIA (rs696) and NFKB1 (-94ATTG insertion/deletion variant, - rs28362491), in PV susceptibility. Forty-four unrelated patients with PV (23 males) were enrolled in the study. Additionally, 77 ethnic matching healthy volunteers (45 males) with no personal or family history of chronic autoimmune or infectious diseases were studied. Strong statistical significant difference was observed between PV patients and controls for polymorphism -94 insertion/deletion ATTG in the promoter region of NFKB1 gene (P = 0.00005). Additional dedicated studies in larger groups of patients of various ethnicities are needed to replicate and confirm the preliminary findings.

Detection of IgG Autoantibodies against Desmocollin-3 in Greek Patients with Pemphigus.

Pemphigus is an autoimmune bullous disorder caused by autoantibodies against desmosomal cadherins. The most common clinical forms are pemphigus vulgaris (PV) and pemphigus foliaceus (PF). Among the numerous proteins that are considered responsible for the cohesion of keratinocytes in epidermis, desmocollin-3 (Dsc-3) has been initially reported to participate in epidermal blistering in mice. There have been reports in which autoantibodies against Dsc-3 have been detected. In PV, a limited number of studies found no presence of IgG or IgA autoantibodies against Dsc-3. In this study we examined sera from Greek patients with PV and PF for the presence of IgG autoantibodies against Dsc-3. Immunoblotting for the detection of autoantibodies against Dsc-3 was performed in sera from all cases. Dsc-3 autoantibodies were not detected in either group (PV and PF). Our results confirm the hypothesis that the pathogenic role of Dsc-3 in epidermal blistering in PV and PF remains controversial.