Presence of hemoglobinopathies in Sicily: a historic perspective.

Sicily, at the center of the Mediterranean, has been the meeting place of Eastern and Western civilizations, and in the Sicilian population the presence of many different alterations in the globin gene clusters can surely be considered testimony of past colonizations. From 1975 to 1994, 100,000 Sicilian subjects were screened by us to monitor the presence of hemoglobin (Hb) structural variants. In this paper we present the data gathered, emphasizing the high incidence (2.5%) of carriers of at least one abnormal Hb, and the great heterogeneity of globin molecular defects on the island. Twenty-six different mutations were identified: the most common occur in the beta-globin gene (beta(S), beta(C), deltabeta(Lepore), beta(G-San José), beta(O-Arab), but also quite frequent is the mutated allele alpha(J-Oxford). The chromosome haplotypes associated with some of them were characterized. Two uncommon Hbs, Copenhagen and D Punjab, and some 18 rare variants complete the wide spectrum of structural alterations of globin genes in Sicily. We think they are de novo mutations prevalently. It is not possible to exclude that the presence of a few of them is related to migratory phenomena, particularly from North Africa and East Asia. Numerous thalassemic alleles complete the picture of globin gene mutations in Silicy.

Survey of sickle cell disease in Italy.

BACKGROUND AND OBJECTIVE: The present study was designed to determine the distribution and severity of sickle cell disease (SCD) in Italy. DESIGN AND METHODS: A questionnaire, requesting information about the cases of sickle cell disease that had been seen during previous years, was sent to all Italian centers of Pediatrics and Hematology. The questionnaire was simple and required personal, hematologic and clinical information. RESULTS: A total of 696 cases were reported. The distribution of registered patients shows that, although the S gene originated mostly in Sicily and Southern Italy, 20% of patients with SCD now live in Central and Northern Italy. The types of SCD reported were as follows: compound heterozygotes HbS-beta thalassemia, (S-Th, 518 cases); homozygotes for HbS, (S-S, 149 cases); compound heterozygotes HbS and another abnormal hemoglobin (21 cases). The population of patients with SCD is younger than the general Italian population. More than 90% of patients have had no crises or only a limited number, namely, up to 6/year. Infections ranged between 0 and 6/year. Splenomegaly was reported in 28% and 80% of adult patients with S-S and S-Th, respectively. The prevalence of gallstones was 48%. INTERPRETATION AND CONCLUSIONS: The survey established that 1) sickle cell disease is widely distributed in Italy; 2) while the clinical spectrum is extremely variable, severe forms are infrequent.

Lymphocyte subsets in kala-azar.

We examined lymphocyte subsets in peripheral blood from children with visceral leishmaniasis both in the active stage of the disease and after recovery. At diagnosis, CD2+ and CD4+ cells showed a significant decrease while CD8+ cells were significantly increased when compared with controls; CD4/CD8 ratio was inverted. All of these alterations returned to normal values 3 months after recovery.

Efficacy of an analysis of lymphocyte subsets in predicting the clinical response to alpha-interferon therapy in thalassaemia patients with chronic infection by hepatitis C virus: a pilot study.

alpha-interferon (alpha-IFN) has been used to treat chronic non-A non-B hepatitis in thalassaemic patients with response rates from 45% to 83%. Unfortunately, treatment with alpha-IFN is associated with side-effects which have a negative effect on the quality of life of the patient. Therefore it would be useful if we could distinguish in advance those patients who would benefit from such therapy from those who would not. In the present study we found that the modification of lymphocyte subsets 20 h after the administration of the first dose of alpha-IFN revealed that relative numbers of T helper lymphocytes (CD4+) increased in three non-responding patients and decreased in five responding patients, whereas those of T suppressor lymphocytes (CD8+), and natural killer cells (CD57+, CD16+) decreased in non-responding patients and increased in responding patients. Therefore analysis of the lymphocyte subsets CD4, CD8, CD57 and CD16 before and 20 h after the administration of alpha-IFN can be used to predict the clinical response to treatment with alpha-IFN.

Population structure of Sicily: beta-thalassemia and HbS.

The population structure of two alleles with similar characteristics, HbS and beta-thalassemia, was studied in the same area in Sicily. It was observed that beta-thalassemia has uniform frequencies over the island, and that HbS shows a South-North cline. A singularity exists for HbS in the town of Butera, where the frequency of the S gene is six times higher than the island average. It was suggested that HbS entered Sicily from Greece (or directly from North Africa) when the beta-thalassemia allele was already established in the Island.

In vitro studies of the modulatory effects of sensory neuropeptides on peripheral blood mononuclear leukocytes of normal and allergic subjects.

The purpose of the present study was to evaluate the modulatory effects of sensory neuropeptides on peripheral blood mononuclear leukocytes of normal and allergic subjects. Peripheral blood mononuclear leukocytes obtained from five normal subjects and from five patients with allergic rhinitis and asthma were incubated with morphine, ACTH, vasoactive intestinal peptide, or substance P at concentrations of 10(-9) M, 10(-7) M, 10(-6) M and suboptimal (0.0125 microgram/mL, 0.025 microgram/mL, and 0.05 microgram/mL) concentrations of PHA. Uptake of 3H-thymidine was evaluated at 72 hours of culture. An inhibitory effect was observed with morphine, ACTH, and substance P while stimulatory effects were seen with vasoactive intestinal peptide, both in normal and in allergic subjects. The results of these preliminary studies provide further evidence for a modulatory role of neuropeptides on the immune function in both normal and allergic subjects.

Non inherited hemoglobin anomalies.

A number of genetic or acquired conditions in which hemoglobin anomalies occur without detectable modifications of globin genes are reviewed. They include increased fetal hemoglobin (alpha 2 gamma 2), variations in hemoglobin A2 concentration, the presence of Hb H (beta 4), Bart's Hb (gamma 4), Hb Köelliker, glycosylated, carbamylated and acetylated hemoglobins.

Immunological changes in beta-thalassemia major patients positive for HTLV-III antibodies.

Antibodies to HTLV-III were found in 6 of 206 Sicilian patients with thalassemia major, aged 1 to 30 years. None of the patients showed clinical signs related to immuno-deficiency syndromes. Immunological investigations carried out in all positive patients showed alterations similar to those found in thalassemic patients without antibodies to HTLV-III. These immunological changes could not depend on the HTLV-III infection, but could be related to the thalassemic condition.

Effect of alpha-interferon on natural killer cell activity and lymphocyte subsets in thalassemia patients with chronic hepatitis C.

The variation of natural killer (NK) cell activity and lymphocyte subsets 20 h after a single test dose of alpha-IFN, was studied in 17 thalassemic patients with chronic hepatitis C. All patients had suspended the alpha-IFN therapy at least 12 months before the study: 10 were considered responders and 7 nonresponders. Also NK cell cytotoxicity after in vitro incubation with alpha-IFN was studied. The administration of a single dose of alpha-IFN increased NK cell cytotoxic activity significantly in the group of responders and in non-responders; moreover the NK cell cytotoxic activity after alpha-IFN in vitro incubation increased both in responders and nonresponders, but to a lesser degree than in healthy controls. Absolute values of CD4+ and CD8+ lymphocytes decreased significantly only in responders. In conclusion, our data suggest that the variation of NK cytotoxic activity and lymphocyte subsets after a test dose of alpha-IFN can be considered a parameter related to IFN biological effects.