Umberto Fagiolo

Thyroid and other organ-specific autoantibodies in healthy ceritenarians

To investigate the prevalence of thyroid autoantibodies in very old subjects, we assayed sera from 34 healthy centenarians (7 men, 27 women; age range 100-108 years) for these antibodies. There was a clear age-dependent increase in prevalence of thyroid autoantibodies in sera from 549 control subjects aged 7-85 years, prevalence in 40 subjects aged 70-85 being significantly greater (p less than 0.001, chi 2) than that in 436 subjects aged less than 50. By contrast, prevalence of thyroid autoantibodies in centenarians was not significantly different from that in controls aged less than 50. Cytofluorimetric analysis of peripheral blood lymphocytes showed a striking age-dependent decrease in total and CD5+B cells (without changes in their ratio), which reached its nadir in centenarians. The age-dependent increase in prevalence of thyroid autoantibodies in the elderly is not seen after the ninth decade of life. What relation this characteristic has to derangement of circulating B cells is unknown.

Changes in circulating B cells and immunoglobulin classes and subclasses in a healthy aged population

The study of 87 adults of different ages, including 15 centenarians, selected for their healthy status, showed that profound changes of humoral immunity occur throughout life. In particuIar, a statistically significant age‐reIated increase of the serum level of immunoglobulin cIasses (IgG and IgA but not IgM) and IgG subcIasses (IgGI, 2 and 3, but not IgG4) was detected. A parallel age‐related decrease of circuIating B cells was also observed. The hypothesis of a complex derangement of B cell function and/or compartmentalization with age is put forward, together with the proposal that healthy centenarians (as representative of successful ageing) may be helpful in identifying the physiological age‐reIated modifications of the immune system.

Inhibitory effect of heparin on skin reactivity to autologous serum in chronic idiopathic urticaria

BACKGROUND Most patients with chronic idiopathic urticaria (CIU) show cutaneous reactivity to intradermal injection of autologous serum. In some cases this reactivity is associated with the presence of autoantibodies directed against IgE or IgE receptors expressed on mast cells, whereas in others no autoimmune mechanisms can be documented. OBJECTIVES The aims of this study were to compare the cutaneous reactivity to serum and plasma samples in a series of patients with active CIU and to address the mechanisms of the inhibitory effect exerted by heparin on the cutaneous responsiveness to the histamine-releasing factors (HRFs) present in CIU serum. METHODS Fourteen patients with CIU were injected intradermally with autologous serum, plasma (anticoagulated by either heparin or EDTA), or serum samples to which heparin had been added. The effects of heparin injection on cutaneous responsiveness to allergens was tested in 5 atopic patients. Moreover, in a set of experiments sera were also adsorbed with Sepharose-conjugated heparin. RESULTS All the patients had positive cutaneous reactions to autologous serum injection. When heparinized plasma was injected, negative reactions were observed in 12 of 14 patients, and a sizable reduction in the wheal-and-flare reactions was recorded in the remaining 2. Compared with results obtained with serum, no substantial change was observed in 6 of 8 patients injected with EDTA-anticoagulated plasma. When heparin was added to serum, abrogation of skin reactivity was seen; nonetheless, no change in the cutaneous response to allergens was associated with locally administered heparin in 5 atopic patients with no history of CIU. Finally, adsorption of CIU sera with solid-phase heparin abrogated the ability to induce cutaneous reactions in 5 of 7 patients, whereas in the remaining 2 a sizable reduction was observed. CONCLUSIONS These data indicate that heparin is able to profoundly inhibit the cutaneous response to HRFs present in the sera of patients with CIU. Although the precise level of action of this heparin-mediated effect is unclear from present data, preliminary evidence seems to indicate that heparin could directly interfere with HRFs present in CIU sera.

Increased cytokine production by peripheral blood mononuclear cells from healthy elderly people.

Mammalian aging is associated with a complex derangement of the immune system. In particular, an impaired capability of T lymphocytes to proliferate when stimulated with a variety of mitogens has been reported. This defect was ascribed to a defective production and utilization of a lymphokirie that is crucial for T-cell proliferation, that is, interleukin-2 (IL-2).I However, immune responses are modulated and regulated by a variety of cytokines other than IL-2, whose production and utilization have not been properly studied during immunosenescence, particularly in humans. For this reason, we thought it worthwhile to study the production of other cytokines in supernatants from peripheral blood mononuclear cell cultures from old subjects. As the production of these cytokines can be deeply affected by the presence of clinical or subclinical pathological conditions, particular attention was paid to the selection of the subjects admitted to the study. Our results suggest that physiological aging is associated with a complex derangement of cytokine production. The production of some of them is increased, whereas that of some others is unaffected.

Thyroid autoimmunity and ageing.

Ageing is associated with the appearance of several serum autoantibodies, including thyroid autoantibodies. The biological and clinical significance of this phenomenon is still unknown, since, with the exception of primary myxedema, the prevalence of clinically overt thyroid autoimmune diseases is not increased in the elderly. The peculiar link between autoimmune thyroid failure and ageing is also underscored by the high prevalence of subclinical hypothyroidism in elderly subjects with positive serum thyroid autoantibodies, and could be the consequence of preferential age-dependent expression of destructive effector mechanisms and/or increased target gland susceptibility. Thyroid autoimmunity and subclinical hypothyroidism have also been implicated in the pathogenesis of other age-associated disorders, in particular coronary heart disease. Interestingly, recent data from our laboratories showed that thyroid autoantibodies are rare in healthy centenarians and in other highly selected aged populations, while they are frequently observed in unselected or hospitalized elderly. Taken together, these data suggest that thyroid autoimmune phenomena are not the consequence of the ageing process itself, but rather might be related to age-associated disease.

Immunogenicity of serum HLA antigens in allogeneic combinations.

Immunization of patients with chronic renal insufficiency with plasma from selected donors elicited lymphocytotoxic antibodies. Analysis of these antibodies with Fab2 blocking assays showed that they are directed to HLA-A,B and to Ia-like antigens. These results indicate that serum HLA antigens are immunogenic in allogeneic combinations.

Life-threatening anaphylactic shock caused by porcine heparin intravenous infusion during mitral valve repair

J Thorac Cardiovasc Surg 2003;126:1194-1195 Gerosa Tomaso Bottio, Giorgio Pittarello, Raffaele Bonato, Umberto Fagiolo and Ginoinfusion during mitral valve repair Life-threatening anaphylactic shock caused by porcine heparin intravenoushttp://jtcs.ctsnetjournals.org/cgi/content/full/126/4/1194 located on the World Wide Web at: The online version of this article, along with updated information and services, is

An immunological and genetic study of patients with gestational diabetes mellitus

The aim of the study was to evaluate the frequency of islet cell (ICA) and insulin (IAA) antibodies and of HLA antigen typing in a group of subjects diagnosed with gestational diabetes mellitus (GDM) in a screening-diagnostic program during pregnancy. ICA, complement-fixing (CF) ICA and other autoantibodies, absolute number and percentage of lymphocyte subpopulations, and HLA antigens were evaluated in 68 women with GDN and compared with those of matched controls. ICA were found in 2 (2.9%) and IAA in 1 (1.5%). Both ICA-positive women had CF-ICA; one of them was receiving insulin therapy, while the other was on a special diet. No correlations were found between ICA and IAA, nor between IAA and insulin treatment. As far as lymphocyte subsets were concerned, we found a significant increase in the absolute number of total and activated (CD3+HLA-DR+) T lymphocytes and a significant increase in the absolute number and percentage of suppressor/cytotoxic T lymphocytes (CD8) and NK lymphocytes (CD57) in GDM patients compared with normal pregnant controls. Concerning frequency for HLA A, B, C, DR antigens in the GDM population, only Cw7 was found to be significantly increased and A10 significantly decreased in comparison with controls. Our study suggests that GDM is a heterogeneous disorder in which few patients present with the immunologic and genetic markers of type 1 diabetes.

Quantitative and qualitative analysis of anti-tetanus toxoid antibody response in the elderly. Humoral immune response enhancement by thymostimulin

In order to explore the humoral primary and secondary response to tetanus toxoid (TT), and to define the possible immunopotentiating effect of the thymic hormone thymostimulin, we studied 13 elderly people, selected according to the Senieur Eurage protocol, vaccinated against TT, an antigen never encountered before. Six of them were treated with thymostimulin before and during the immunization protocol. Specific anti-TT antibody level measurement and spectrotypic analysis were performed on the sera collected from the subjects at different times over the immunization protocol. In addition, spontaneous in vitro production of anti-TT antibodies as well as cutaneous delayed hypersensitivity reactions were also studied. Only one patient showed a detectable humoral immune response after the first immunization. After the booster, four of six thymostimulin-treated individuals, compared with only two of seven controls, showed in vivo anti-TT humoral response; at the same time, spontaneous anti-TT production was detected in peripheral blood mononuclear cells from five of six thymostimulin-treated individuals but only three of seven untreated controls. These differences were highly significant (p < 0.0001). In addition, only in thymostimulin-treated subjects were the levels of serum anti-TT antibodies 14, 21 and 28 days after the booster significantly (p < 0.05) higher than the baseline values. The spectrotypic analysis of anti-TT antibodies performed by isoelectric focusing and reverse blotting showed total agreement with the results from enzyme-linked immunosorbent assay.(ABSTRACT TRUNCATED AT 250 WORDS)

Study of Some Early Immunological Parameters in Aging Humans

We studied the correlation between the in vitro lymphocyte proliferative response and some early parameters of lymphocyte activation in aged people. While a consistent number of elderly subjects showed significantly decreased proliferative responses to mitogen stimulation, interleukin-1 (IL-1) production and IL-2 receptor/DR antigen expression were comparable to those of young controls. The reduction in IL-2 production observed in some aged donors did not correlate with the decreased proliferative activity in response to mitogen. Moreover, addition to the cultures of recombinant IL-2 was not capable of restoring the proliferative response to normal levels. These data on the whole seem to argue against a primary involvement in age-associated lymphocyte hyporesponsiveness of an alteration in the early phases of lymphocyte activation engaging the complex lymphokine/receptor network.