Impairment of gamma/delta T lymphocytes in elderly: implications for immunosenescence

Gamma/delta T lymphocytes cells recognize the antigen in a non-classical way and are considered the third branch of the immune system devoted to defend the integrity of the body. Ageing is characterized by an impairment of the main way of protection (the adaptive branch) but, successfully aged people show compensatory mechanisms of defense such as proneness to inflammation. Moreover, very old subjects show an increased number of NK cells. We have previously demonstrated that gamma delta T lymphocytes are reduced in elderly. In the present paper we have studied some characteristics of these cells to evaluate the possibility that these cells might balance the decreased action of the adaptive branch in successfully aged people. Cytofluorimetric analysis of cells collected from young, old and centenarian subjects has been used to evaluate the ability of these cells to expand in vitro. Here we demonstrate that gamma delta T cells are impaired in the ability to proliferate to different stimuli such as isopentenyl pyrophoshate, that select gamma delta T lymphocytes bearing delta 2 chain, other than to phytohemagglutinin and anti-CD3 that are polyclonal activators. Moreover, we demonstrate that gamma delta T cells in aged and centenarians show an enhanced sensitivity to undergo apoptosis induced both by alpha-Fas and TNF-alpha. All together these data suggest that gamma delta T lymphocytes are impaired in elderly and suggest that the reduced ability to proliferate and the reduced number of circulating gamma delta T lymphocytes is due to the proneness to apoptosis. Finally on the basis of these data, we conclude that gamma delta T lymphocytes, do not participate in the remodeling of the immune system due to the reduction of classical T cell response and replacement by NK cells in elderly.     

Pregnancy as a risk factor for restless legs syndrome

Pregnant women have at least two or three times higher risk of experiencing restless legs syndrome (RLS) than the general population. These data come from few epidemiological studies finding an 11-27% prevalence of RLS during pregnancy. Women affected by pre-existing RLS often complain of worsening symptoms during pregnancy. This is usually a benign form of RLS, with the highest degree of severity in the third trimester and a tendency to disappear around delivery. The causes of the association between RLS and pregnancy are unknown. The most debated hypotheses are: metabolic alterations, with particular regard to iron and folate deficiency; hormonal influences related to the increase of prolactin, progesterone and estrogens during late pregnancy; and the changing motor habits and psychological state of pregnant women. The importance of folate and iron supplementation during pregnancy in preventing RLS is unclear. RLS in pregnant women is frequently unrecognized; they are often worried about the symptoms and do not receive an adequate explanation by doctors.     

Mutational analysis of 206 families with cavernous malformations

OBJECT: A gene contributing to the autosomal-dominant cerebral cavernous malformation (CCM) phenotype, KRIT1 (an acronym for Krev Interaction Trapped 1), has been identified through linkage analysis and mutation screening. The authors collected blood samples from 68 patients with familial CCM and 138 patients with apparently sporadic CCM as well as from their families, in an effort to characterize the prevalence and spectrum of disease-causing sequence variants in the KRIT1 gene. METHODS: The authors used single-strand conformational polymorphism analysis to identify genomic variants in KRIT1, which were sequenced to determine the specific mutation. Among 43 Hispanic-American kindreds who immigrated to the southwestern US from northern Mexico, 31 share an identical founder mutation. This Q455X mutation is found in 18 (86%) of 21 persons with a positive family history and in 13 (59%) of 22 persons with apparently sporadic CCM. This mutation was not found among 13 persons with CCM who were recruited from Mexico. These findings establish the key role of a recent founder mutation in Hispanic persons with CCM who live in the US. Although nearly all Hispanic families in the US in which there are multiple CCM cases linked to the CCM1 locus, only 13 of 25 non-Hispanic CCM-carrying families have displayed evidence of linkage to the CCM1 locus. Among these 13 families, the authors identified eight independent mutations in nine kindreds. They identified four additional mutations among 22 familial CCM kindreds with no linkage information, bringing the total number of independent mutations to 12. Inherited KRIT1 mutations were not detected among 103 non-Hispanic persons in whom a family history of CCM was rigorously excluded. CONCLUSIONS: All mutations were nonsense mutations, frame-shift mutations predicting premature termination, or splice-site mutations located throughout the KRIT1 gene, suggesting that these are genetic loss-of-function mutations. These genetic findings, in conjunction with the clinical phenotype, are consistent with a two-hit model for the occurrence of CCM.     

Leishmania antibodies in children’s serum samples in correlation with the disease in dogs

Sera of 489 children from Northern Greece aged between 6 months and 15 years of age and aflicted with different clinical entities, were tested for anti ? Leishmania infantum specific IgG and IgM antibodies, using an ELISA (enzyme linked immunosorbent assay) technique. In this survey, a remarkably high percentage (8.5%) of hospitalized children reacted positively to this method. Twenty three out of 489 children (4.7%) had IgG antibodies, seventeen (3.5%) IgM, while two (0.4%) had both IgG and IgM antibodies against soluble antigen of L. infantum promastigotes. Females had a higher seropositivity than males. The highest prevalence was observed in males aged between 6 months and 5 years old (10 out of 19), while the lowest was observed also in males aged between 11 and 15 years old (5 out of 11). Seropositivity rate was higher in children below 5 years of age. Some epidemiologic, as well as clinical data of canine Leishmaniosis from Northern Greece are discussed.     

Toxocarosis as zoonosis. A review of literature and the prevalence of Toxocara canis antibodies in 511 serum samples

A total of 511 serum samples from children aged between 6 months to 15 years old, with different clinical signs-living in the region of Northern Greece - were tested by ELISA (enzyme links immunosorbent assay) technique, for the detection of specific IgG and IgM antibodies against T. canis antigen. The reason IgM was detected was because IgM levels are elevated in the acute phase of toxocara infection, in spite of their notorious non-specificity. In this seroepidemiologic survey of children, a remarkably high percentage (12.5%) reacted positively to this method. Sixteen (3.1%) out of 511 sera showed IgG antibodies, 43 (8.4%) showed IgM, while 5 (1%) showed both IgG and IgM antibodies against T. canis E/S (excretory - secretory) antigen. Females were significantly more infected than males. Seropositivity rate was highest in children over the age of 10.     

Seasonal variability of non-specific bronchial responsiveness in asthmatic patients with allergy to house dust mites.

The aim of the study was to assess the seasonal variability of non-specific bronchial responsiveness to methacholine in allergic asthma. One hundred sixty-five patients (83 male and 82 female) entered the study: 86 subjects (group A) with allergy exclusively to mites and 79 (group B) with concomitant allergy to pollens, e.g., "Graminae" and "Parietaria." Inclusion criteria were the absence of sensitization to other allergens, no smoking habit, withdrawal from steroids, bronchodilators, sodium cromoglycate, and antihistamines for at least four weeks before enrollment, FEV1 > 70% of the predicted value, and absence of other respiratory diseases and of upper and lower respiratory tract infections for at least one month before the methacholine challenge. None of the patients had been previously treated with specific immunotherapy. Subjects of each group (A and B) underwent methacholine challenge at first visit and were divided into four subgroups according to the period when the challenge was performed. Subgroups A1 and B1 performed the challenge in December, January, and February; subgroups A2 and B2 in March, April, and May; subgroups A3 and B3 in June, July, and August; subgroups A4 and B4 in September, October, and November. PD20 values were expressed as the natural logs of the cumulative dose of methacholine causing at least a 20% fall in FEV1. Statistical analysis was carried out using multiple group analysis and Student's t-test. Results showed that the highest non-specific bronchial responsiveness was observed in autumn (ln PC20 = 4.54 +/- 1.51) in patients allergic to mites only (group A), and in summer (ln PC20 = 4.72 +/- 2.11) in those of group B. Multiple group analysis showed statistical significant differences between subgroups within each group (group A, p = 0.039; group B, p < 0.001). In patients allergic exclusively to house dust mites (group A), multiple comparisons and Student's t-test showed statistically significant differences between non-specific bronchial responsiveness (NSBR) assessed in autumn and those of other seasons (winter, p = 0.002; spring, p < 0.001; summer, p = 0.082). These results confirm that the level of allergen exposure may influence NSBR. Mite-allergic patients showed an increase of NSBR in autumn, possibly as a consequence of higher indoor mite concentration. However, mite- and grass-allergic patients had wider variations of NSBR, possibly reflecting changes in seasonal pollen concentration.     

Dry eye in allergic conjunctivitis: role of inflammatory infiltrate

Dry-eye associated symptoms are frequently present in patients affected with allergic conjunctivitis. We evaluated the relationship between ocular inflammation and the tear film parameters in patients affected with chronic allergic conjunctivitis. Eighty-two subjects (age 23.00 ± 7.61: range 10-40) affected with chronic allergic conjunctivitis and thirty age- and sex matched healthy controls were enrolled. In all patients tear film qualitative and quantitative tests were performed. To determine the immune activation state, conjunctival biopsies were obtained from the inferior conjunctival fornix. Immunocytochemical markers for CD45RO, CD8, CD20 and EG2 (monoclonal antibody binding eosinophil cationic protein) were evaluated semiquantitatively. All tear film tests were found altered. They were reduced in allergic patients (p<0.001). In conjunctival biopsies of allergic patients a very high number of CD45RO+ and EG2+ cells were found (p<0.001): a lower number of CD45RO+ cells and no EG2+ cells in control biopsies were found. Multivariate analysis showed a significant relationship between tear tests and conjunctival infiltrate (CD45RO+ and EG2+): The tear film alterations are strictly related to the conjunctival immune infiltration. In particular, the reduction of the mucin-related component of tear film can be related to the toxic effect of the granule cationic proteins released by the conjunctival activated eosinophils (EG2+ cells).