The Presence of HLA-A Bw4-80I KIR Ligands Could Predict "Difficult-to-Treat" Psoriasis and Poor Response to Etanercept.

BACKGROUND: Psoriasis is an immune-mediated dermatosis with a wide genetic predisposition. The immunogenetic background, specifically interactions between human leukocyte antigen (HLA) class I ligands and killer-cell immunoglobulin-like receptor (KIRs), have functional significance in modulating natural killer (NK) cells and can influence susceptibility and response to biological therapy. OBJECTIVE: The main aim of this study was to correlate HLA-A and -B KIR ligands with response to biological therapy in patients with psoriasis. METHODS: HLA-A and -B polymorphisms were determined in 48 patients (35 males and 13 females), with a mean of 22 years of disease (range 8-55). All patients were treated with biological therapy (adalimumab, etanercept, infliximab, or ustekinumab) for at least 6 months. RESULTS: This study identifies, with statistical significance, the presence of at least one ligand HLA-A Bw4-80I in the "poor-responder" population (patients who needed two or more biologics) compared with the "responder" population (patients with good response after a single biological drug) (47.62 vs. 11.11%; p = 0.006) as well as in "non-responders to etanercept" compared with "responders to etanercept" (52.63 vs. 5%; p = 0.001). CONCLUSION: Our preliminary results suggest that at least one ligand HLA-A Bw4-80I could be associated with "difficult-to-treat" psoriasis and that this ligand may reduce the probability of response to etanercept, producing more tumor necrosis factor (TNF)-α and neutralizing NK activity through a predominance of activating KIR. The ab initio identification of genetic markers of response to biologic therapy could improve the efficacy and economic impact of these agents.

Mycosis fungoides: association of KIR ligands and HLA-DQB1*05 with bad prognosis of the disease.

BACKGROUND: Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma. We previously reported that the prognosis of MF patients is not only related on clinical variables but it is also associated with peculiar HLA alleles. Until today, the association of HLA ligands for KIR with the prognosis of the disease has not yet been analysed. OBJECTIVE: We investigated the frequency of HLA ligands for killer cell Immunoglobulin-like receptors (KIRs) in MF patients, evaluating if the presence of particular HLA alleles that are ligands for KIR may have prognostic value. METHODS: The study includes 46 Caucasian MF patients that, between 1993 and 1997, underwent HLA genomic typing. All patients were diagnosed and followed up from 1977 to 2012 (mean follow-up of 11 years). RESULTS: MF patients have been divided into two groups (long survivors and dead patients). We noticed that the HLA-Bw6/Bw6 specificity increased among the group of seven dead patients compared to the group of 39 long survivors (71.4% vs. 41.0%, P = ns, OR = 3.59), while in the long survivors group the HLA- Bw4/Bw4 specificity increased when compared to dead patients (23.0% vs. 0%, P = ns). Moreover, we observed that six of the seven dead patients had HLA-DQB1*05; the phenotypic frequency of this HLA allele, in dead and long survivors patients, was 85.7% and 23.0% respectively (P = 0.004; OR = 20). CONCLUSION: Our observations suggest that the presence of the HLA-DQB1*05 alleles characterizes the patients with the poorest prognosis in MF. In addition, absence of the KIR-ligand epitope HLA-B Bw4 showed a trend of being more prominent in MF patients with the poorest prognosis.

IgA anti-epidermal transglutaminase autoantibodies: a sensible and sensitive marker for diagnosis of dermatitis herpetiformis in adult patients.

BACKGROUND: Dermatitis herpetiformis (DH) is a rare gluten-sensitive blistering itchy skin disease, strictly related to coeliac disease (CD). Direct immunofluorescence, demonstrating IgA granular deposits localized either in the dermal papillae or along the dermo-epidermal junction, is currently the gold standard for diagnosis of DH. It has been shown that DH immunocomplexes contain epidermal transglutaminase (eTG) and that sera from patients with DH contain antibodies specifically directed against eTG. OBJECTIVES: We studied the usefulness of serum eTG antibodies in discriminating between DH, CD and other gastrointestinal and dermatologic diseases. METHODS: eTG antibodies were tested in 308 adult patients' sera: 44 patients with untreated dermatitis herpetiformis (UDH), 99 patients with untreated coeliac disease (UCD), 70 dermatological controls and 95 gastrointestinal controls. RESULTS: In UDH eTG antibody levels were significantly higher than in DH patients on gluten-free diet, UCD, gastrointestinal controls and dermatological controls. In UCD eTG antibodies strongly correlated with tissue transglutaminase (tTG) antibodies, whereas in UDH no significant correlation was observed. CONCLUSION: Serum IgA eTG antibody determination can efficiently distinguish UDH from other dermatological itchy diseases and is highly sensitive to gluten-free diet.

Prevalence, severity and clinical features of psoriasis in fingernails and toenails in adult patients: Italian experience.

BACKGROUND: Psoriasis is a chronic inflammatory skin disease affecting 2.0-6.5% of the European population. Although the most striking clinical features of psoriasis involve the skin, other organs including nails and joints may be affected in a substantial proportion of patients. Literature reports nail involvement in 10-56% of psoriatic patients, with common physical and social impairment. However, the precise prevalence of specific clinical features of nail psoriasis is somewhat under-reported. OBJECTIVES: Our cross-sectional study aimed at describing the prevalence and the clinical features of nail involvement in adult psoriatic patients in a psoriasis referral centre in northern Italy. METHODS: A total of 178 (124 men, 54 women) consecutive adult patients (≥18 years old) with psoriasis were included. Psoriasis Area and Severity Index (PASI) and Nail Psoriasis Severity Index (NAPSI) scores were calculated for each patient. Relevant medical history was recorded. RESULTS: Nail involvement was present in 137 (99 men, 38 women) patients (76.9%). The most common nail abnormality was onycholysis, followed by crumbling, subungual hyperkeratosis, pitting and discoloration. Pitting and onycholysis were the most prevalent patterns observed in fingernails, whereas onycholysis and crumbling were the most frequent changes detected in toenails. The most frequently and severely affected nails were the fourth fingernail and the first toenail. The average PASI score was higher in individuals with nail involvement (12.0 vs. 8.7, P = 0.06). Nail changes were present in 85.7% of patients with psoriatic arthritis. CONCLUSIONS: Our study confirms that nail involvement may be overlooked in psoriasis patients. Different psoriatic patterns in the nail affect specific digits more frequently.