A. De Silvestri

Personality traits in childhood and adolescent headache

We evaluate personality traits, anxiety and depression in a population of paediatric and adolescent patients, correlating personality characteristics with headache and sociodemographic variables. The clinical features of headache include specific personality traits. We report a clinical study of 57 patients (age 8–18 years), divided up as follows: 12 migraine with aura, 29 migraine without aura and 16 tension-type headache. One of Cattels tests was administered to every patient; the Childrens Depression Inventory test was administered to 53 patients and the Test Anxiety Inventory test to 43 subjects. The scores obtained by every patient in each test were correlated with the characteristics of headache and with sociodemographic data. We found that patients affected by idiopathic headache share some personality traits, mainly emotional rigidity and tendency to repress anger and aggression. These traits do not seem to be correlated with sociodemographic data and the duration of headache: we considered these as characteristic of migrainous patients.

Critical evaluation of the variants influencing the clinical response of vitiligo: study of 60 cases treated with ultraviolet B narrow‐band phototherapy

Background  The treatment of vitiligo is still a challenge, but ultraviolet B narrow‐band (UVB‐NB) therapy has been recently reported to be an effective and safe therapeutic option in patients with vitiligo.

Inflammation and Atherosclerosis: The Role of TNF and TNF Receptors Polymorphisms in Coronary Artery Disease

Inflammation plays an important role in the pathogenesis of atherosclerosis and coronary syndromes; moreover, various lines of evidence suggest that genetic factors contribute significantly to the risk of coronary artery disease (CAD). Through its effects on endothelial function, coagulation, insulin resistance and lipid metabolism, the proinflammatory cytokine TNF could be involved in cardiovascular pathophysiology. The aim of our study is to analyze whether TNF gene promoter (-308 G/A; −857 G/A) and TNF receptor polymorphisms (TNFR1 MspA1 I exon 1 and TNFR2 Nla III exon 6) show involvement in CAD predisposition in a group of Italian patients compared with healthy controls. Genotyping was performed by PCR-RFLP. Consecutive Italian patients with angiographically proven CAD (n= 248) were compared with controls (n=241), matched for age, sex and geographical origins. CAD patients showed a higher frequency of the TNF −308 A allele than healthy controls (p=0.046). After stratification according to risk factors for CAD, our analysis revealed that CAD patients with diabetes (p=0.042) and CAD patients without hypertension (p=0.0495) displayed a higher frequency of the TNF −308 AA genotype compared with healthy controls. Our data stress the inflammatory nature of CAD and show a possible involvement of TNF −308G/A promoter polymorphisms in the predisposition to the development of this disease. The less frequent A allele seems to be a predisposing factor for development of CAD in particular pathological settings associated with the disease itself, such as diabetes.

Hierarchy of baby-linked immunogenetic risk factors in the vertical transmission of hepatitis C virus

Mother-to-infant transmission of Hepatitis C Virus (HCV) represents the major cause of pediatric HCV infection today. Immunogenetic influence has been poorly investigated and mainly confined to HLA-class II serological polymorphisms. Among 290 parities, 135 from Pavia and 155 from Bergamo, of HCV-RNA-infected Italian women, 21 babies (7.24%) were HCV-RNA positive at birth and steadily positive over 20 months of life. All the 21 infected babies and 44 randomly selected uninfected ones, born to HCV-RNA+ mothers but steadily negative for HCV-RNA during a follow-up of 2 years, and their mothers were investigated for HLA-G, -C, -DRB1, -DQA1 and -DQB1 genomic polymorphisms. Among the different covariates, HLA-Cw*07, -G*010401, -DRB1*0701, -DRB1*1401 and homozigosity for HLA-G 14bp deletion can be considered as risk factors for HCV vertical transmission. On the contrary, protection was conferred by the HLA-DQB1*06, -G*0105N, -Cw*0602, DRB1*1104 and -DRB1*1302 alleles. Our initial question was: has the immunogenetic profile any role in the protection of the fetus growing in an infected milieu and, if so, is it independent from the other non-immunogenetic parameters? The answer to both questions should be yes.

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.

Non-invasive evaluation of tacalcitol plus puva versus tacalcitol plus UVB-NB in the treatment of psoriasis: "right-left intra-individual pre/post comparison design".

Photochemotherapy with psoralen plus ultraviolet A (PUVA) and phototherapy with UVB narrow band (UVB-NB) are used in the treatment of psoriasis. Numerous studies have shown that the additional administration of either topical or systemic antipsoriatic agents may effectively increase the efficacy of these therapies. This study aimed to compare through objective data the efficacy of topical tacalcitol in combination with PUVA or UVB-NB versus PUVA and UVB-NB monotherapy in the treatment of mild to moderate chronic plaque psoriasis. Modified Psoriasis Area and Severity Index (PASI) score, transepidermal water loss (TEWL) and stratum corneum hydration were used to monitor the restoration of skin barrier in the psoriatic plaques of 40 patients during photochemotherapy. The study was a right-left, intra-individual, pre/post comparison trial. PUVA and UVB-NB treatments were given three times a week. On those plaques localized on the right side of the body tacalcitol ointment was applied once a day, in the evening. Corneometry, TEWL and modified PASI score were used to evaluate the response to the treatment at baseline, one month and two months. Thirty-six of the forty enrolled subjects completed the study. The comparison between combination treatments and the PUVA/UVB-NB monotherapy showed no significant differences with regard to modified PASI index. However, significant differences were recorded with regard to TEWL and corneometry. The combination of tacalcitol plus PUVA or tacalcitol plus UVB-NB restored epidermal barrier functions as well as skin hydration faster than PUVA or UVB-NB monotherapy (TEWL: p=0.0050 and corneometry: p=0.003). The combination of tacalcitol plus UVB-NB allowed a better restoration of skin barrier functions than tacalcitol plus PUVA (p=0.013). In conclusion, the combination of tacalcitol plus PUVA or plus UVB-NB improves the therapeutic result. In addition, the data from TEWL and skin hydration suggest a means in which tacalcitol plus UVB-NB induces a better normalization of skin biophysical parameters.

Molecular study of receptor for advanced glycation endproduct gene promoter and identification of specific HLA haplotypes possibly involved in chronic fatigue syndrome.

The receptor for advanced glycation end product (RAGE) is thought to play an important role in inflammation. Chronic Fatigue Syndrome (CFS) is a long-lasting fatigue that compromises at least 50% of a subjects daily activities without other known cause. Immune dysfunction has been implicated and an association with a peculiar genetic cytokine profile, predisposing to an immunomodulatory response of inflammatory nature, was found. The aim of this study is to analyse RAGE polymorphisms and HLA-DRB1 alleles in seventy-five Italian CFS patients and 141 controls matched for age, sex and ethnicity. These two groups underwent genomic study for RAGE –374T/A and –429C/T promoter polymorphisms; moreover, 46 patients and 186 controls were typed for HLA-DRB1 at low resolution molecular level. Of these, 31 patients and 99 controls also underwent “high resolution analysis” to define the HLA-DRB1*11 and DRB1*13 alleles. The haplotypes RAGE-374T, DRB1*04; RAGE-374T, DRB1*09; RAGE-374T, DRB1*11; RAGE-374A, DRB1*13; RAGE-429T, DRB1*04 and RAGE-429C, DRB1*11 were significantly more frequent in CFS patients, whereas RAGE-429C, DRB1*07 would seem protective. A significantly lower frequency of DRB1*1104 (5.4% vs 12.9% p=0.04, OR=0.39) and a significantly higher frequency of HLA-DRB1*1301 (13.0% vs 5.1% p=0.006, OR= 2.79) were found in CFS patients. A synergic effect was observed with RAGE polymorphism. The OR values strengthened in the following cis combinations: RAGE-374A, HLA-DRB1*1104 (OR=0.27) and RAGE-374A, HLA-DRB1*1301 (OR=6.23). HLA haplotypes rather than single alleles of RAGE or of DRB1 genes seem to be involved in CFS, probably including a subregion of major interest.

HLA-A*01 is associated with late onset of Alzheimer's disease in Italian patients.

In this study, the distribution of HLA-A alleles was analyzed in Italian Alzheimers Disease (AD) patients. Interaction between HLA alleles, APOE genotypes, age of onset, and gender were also analyzed. The results were compared to those obtained in healthy controls (HC). One hundred-seventy-three AD patients and 258 age-and-sex-matched healthy controls were enrolled in the study. AD patients were classified according to age at the onset of disease using quartiles of the distribution. HLA-A genotyping was performed by PCR-SSP; APOE genotyping was performed by RFLP. A correlation between late disease onset and HLA-A*01 was observed. Thus, HLA-A*01, calculated as number of alleles, was significantly more present in patients with age of onset > 74 years than in HC (20% vs 10.5%; p=0.014); the distribution of this allele was skewed also in patients 68.1–74.0 years of age (16.3%), even if the difference did not reach statistical significance. The relative risk ratio (RRR) of AD onset calculated by a multinomial logistic regression adjusted for sex and presence of APOE-4 confirmed a significant association of HLA-A*01 with AD onset > 74.0 years of age (RRR=2.2; 95%CI: 1.1 – 4.6; p=0.033). A high RRR (2.04) was also present in patients 68.1 – 74 years (p=0.064). Lower age of disease onset did not correlate with HLA-A*01. Data herein suggest that the presence of HLA-A*01 results in delayed AD development, even in patients carrying APOE-4. These results could offer new insights into the etiopathogenesis of Alzheimers disease.

Escherichia coli specific secretory IgA and cytokines in human milk from mothers of different ethnic groups resident in northern Italy.

Breast milk supplies many bioactive components. Neonates protection from pathogenic bacteria is mainly attributable to secretory IgA antibodies present in human milk in an amount depending on previous antigenic exposure. To bring new details into the field of immunological memory in secretory immunity, we evaluated the production of s-IgA specific for E. coli (E. coli s-IgA), and of proinflammatory (IL-6 and IL-8) or anti-inflammatory (IL-10) cytokines in the milk of mothers of different ethnic groups exposed in the past to poor conditions, but nowadays living in Italy in adequate conditions. Mothers from Italy, Africa, Asia and Eastern European Countries were included in the study. Anti-E. coli s-IgA, IL-6, IL-8 and IL-10 were determined by ELISA. Breast milk of all the foreign mothers presented higher levels of E. coli s-IgA than Italians, and for Asian and African mothers were significative (p=0.031 and p=0.015, respectively). Milk from women of Eastern European Countries revealed the highest IL-8 levels (p=0.026), while milk from Asian women presented the greatest concentration of IL-6 (p=0.04); however, the Africans reported the lowest concentrations of IL-10 (p=0.045). Since all the mothers had been living in Italy for some time, we believe that the presence of high levels of E. coli s-IgA, supported by high levels of pro-inflammatory cytokine, is part of a persisting immunological secretory memory.

Probable ancestors of Hungarian ethnic groups: An admixture analysis

The history of Hungary starts in the 9th century with the arrival of the Magyars in the Carpathian Basin. They spoke, like modern Hungarians, an Uralic language belonging to the Finno‐Ugric language group. Their original composition probably included Iranian and Turkish people, while other populations were already present in the territory (Avars, Slavs, Germans). Some of the Hungarian ethnic groups claim to be descendants of ancient Magyars settlers (such as the Örség), others of Huns, Turks or Iranians. We collected and compared the previously published gene frequencies of eight ethnic groups and seven hypothetical ancestral populations, including Uralics, applying a model of admixture. The results, most of which confirm historical hypotheses or the oral tradition, show that only one ethnic group (Örség) highly resembles the Uralic population.