Immunogenetic heterogeneity and associated autoimmune disorders in myasthenia gravis: a population-based survey in the province of Ferrara, northern Italy.

INTRODUCTION: The well-established relationship between myasthenia gravis (MG) and HLA antigens varies among different ethnic groups. In Caucasians B8 and/or DR3 alleles have been found associated with young MG women without thymoma and with high titres of acetylcholine-receptor antibody (AChR Ab). An increased frequency of haplotype HLA-A3, B7 and/or DR2 has been observed in older MG patients with low AChR Ab levels. So far, there is no convincing evidence for an association between a specific haplotype HLA and ocular MG or MG with thymoma. MG subjects often show other concurrent autoimmune disorders suggesting a more general inherited predisposition to autoimmunity. We performed a community-based study to verify the HLA-A, B, C, DR and DQ profile on ethnically homogeneous MG patients and with the aim to estimate the frequency of concurrent autoimmune diseases and to compare HLA phenotypes to autoimmune status in different MG patients groups. METHODS: Forty-seven patients, living in the province of Ferrara, were followed-up in our neurologic department and typed for HLA Antigens. In addition a set of immunological laboratory tests was performed. RESULTS: We found a trend towards an increased B8 and DR3 frequencies in total affected population; an association between B8 allele and early onset of generalized MG sustained by thymic hyperplasia. The DR3 allele is statistically associated with the presence of additional autoimmune disorders. CONCLUSIONS: Our data support the hypothesis of a genetically-based heterogeneity of the disease and show an increased prevalence of associate autoimmune conditions in MG patients.

HLA antigens and multiple sclerosis in the Province of Ferrara, northern-Italy: a community-based study.

The association between Multiple Sclerosis (MS) and DR2 HLA antigen is well known in Caucasoids. In the past few years a significant correlation has been found between DQwl and MS in North-East Scotland and in several other countries. In previous HLA studies in Italian MS patients, a lack of any association or an increased frequency of DR2 have been observed; however, the results of most Italian surveys derive from heterogeneous sample of affected individuals. This study was carried out in a homogeneous population of patients living in and originating from the province of Ferrara, Northern-Italy. Among the prevalence cases, 116, indigenous, unrelated patients, were typed for HLA-A-B, -DR and DQ antigens. The comparisons with 185 healthy individuals, originating from the same area, revealed an increased prevalence of DR2 antigen in Ferrara MS patients. This antigen does not appear to be related to the clinical variables of the disease.

The distribution of HLA antigens in Italy.

Human histocompatibility (HLA) gene frequencies were studied in the Italian population. A random sample of healthy individuals born in several Italian regions and provinces was studied to estimate HLA-A, -B, -C and -DR gene frequencies using the maximum likelihood method. The goodness of fit to Hardy-Weinberg proportions was evaluated by the likelihood ratio statistics. Different Italian regions and provinces show significant differences in the HLA alleles, providing further evidence for the genetic heterogeneity in the Italian population. This heterogeneity is also displayed by a synthetic geographical representation which uses colour to map the most informative gene differences. Statistically significant gametic associations between HLA-A, -B, -C and -DR loci are reported. The difference between northern and southern Italy and between continental Italy and Sardegna is clearly shown also by their heterogeneous linkage disequilibria.

Impaired HLA capping capacity of peripheral blood lymphocytes in Duchenne muscular dystrophy.

The cap capacity in nine Duchenne muscular dystrophy (DMD) patients and in 23 healthy male subjects (14 adults and nine neonates) has been investigated by inducing capping of HLA molecules. The evaluation of capping percentages ranged in healthy controls from 44 to 61 with a mean value of 53.39 +/- 4.89, while DMD patients displayed cap capacity of percentages varying from 15 to 38 with a mean value of 31.5 +/- 7.42. Statistical significance of the differences between the two groups, assessed by the Mann-Whitney U test, was p less than 0.00003. A correlation was found in DMD patients between cap capacity and age (tau = +0.657, p = 0.012). The results confirm previous reports of Ig capping impairment noted in B cells of the whole lymphocyte population, supporting the hypothesis of a systemic cellular defect in DMD patients. The data obtained suggest that HLA capping could overcome some of the technical difficulties of Ig capping and could be used as a diagnostic aid in antenatal detection of DMD.

[Occurrence of HLA B27 antigen in ankylosing spondylitis in Italy]. / Contribution à l'étude de la fréquence de l"antigène HLA B27 dans la spondylite ankylosante en Italie.

39 individuals from Middle and South Italy were selected for being affected by ankylosing spondylitis (AS) (N = 22) or by sacroiliitis (SI) (N = 17) and typed for the HLA system antigens. 320 healthy individuals were typed as control population. The following phenotypic frequencies of HLA-B27 were found; 68% in AS patients, 71% in SI patients and 5% in controls. The frequency of B27 observed among our AS patients is lower than those observed in other caucasian patients. Our data may be explained either by a genetic hypothesis or by an environmental hypothesis; data reported by other authors let we believe that the last one is more reliable.

Glucose-6-phosphate dehydrogenase Ferrara. A new variant of g-6-PD identified in Northern Italy.

A new variant of glucose-6-phosphate dehydrogenase (G-6-PD) has been discovered in Northern Italy, in the district of Ferrara. This variant is characterized by high decrease of red blood cell enzyme activity (less than 5% of normal), high affinity for G-6-P and NADP, increased utilization of deamino-NADP and 2-deoxy-G-6-P, and faster electrophoretic mobility in the buffer systems commonly used for the classification of the G-6-PD variants. The new G-6-PD type was never associated with clinical manifestations in any cases except neonatal jaundice in some of the newborns with this enzyme deficiency. The frequency of the new variant in the Ferrara district indicates that it has probably appeared in this area by mutation some centuries ago. It is suggested that this variant should be named G-6-PD Ferrara.