No significant differences were observed comparing the CD subjects group genotype frequencies with control and  vex 95-year-old healthy subject groups (3 2 contingency tables, chi-squared test). Oy  No significant differences were observed comparing controls and 95-year-old healthy subject groups (3 2 con- tingency tables, chi-squared test).

 TGF- 2 POLYMORPHISM IN CD

Statistics

the other hand, the authors have recently re- ported that celiac patients show a proinflam- matory cytokine genetic profile characterized by the contemporaneous presence of both the  tumor necrosis factor- –308A and the inter- feron-(cid:4) =——_——+6 874T allele-positive genotypes.4 Both alleles are associated with an increased pro- duction of the two major proinflammatory cy- tokines; and it is well known that a high proin- flammatory profile is considered detrimental to life expectancy, facilitating a rise of age-associ- ated diseases (including neurologic diseases, osteoporosis, and malignancy) that are consid- ered among the major late CD complications.3 Additionally, an anti-inflammatory cytokine genotype profile might be associated with an extended life expectancy.13 In this view, the lack of difference in genetic frequencies of ACAA Ins/Non-Ins alleles between CD pa- ah| >S tients and 95-year-old healthy control groups  might suggest that this TGF- 2 polymorphism is not involved in the complex genotypes as- sociated with successful or unsuccessful aging. In addition, one can speculate that the geno- type profile associated with CD susceptibility might be detrimental for long life expectancy and studies of CD genetic assets might suggest candidate genes for antiaging strategies.

Allele frequencies were evaluated by gene count. The data were tested for the goodness of fit between the observed and expected geno- type values (Hardy-Weinberg equilibrium). Chi-squared tests (Graphpad Instat package, Graphpad Software Inc., San Diego, CA) were performed to calculate significant different genotype distribution among the three groups of subjects. Because multiple comparisons were made, Bonferroni’s correction was applied, multiplying obtained p-values for the number of genotypes detected.

RESULTS AND DISCUSSION

As reported, TGF- 2 is involved in the con- trol of inflammatory responses, activating tis- sue remodeling,9 and induction of IgA isotope switching in B cells.5,6 Considering these func-  tions, the authors speculated that a TGF- 2 genetic background, capable of influencing  TGF- 2 production, might be involved in CD  susceptibility. Actually, the lack of TGF- acti- vation induced by antitransglutaminase anti- bodies is one of the central pathogenetic mech- anisms in CD, as suggested by Lionetti et al.7 The authors’ data demonstrate that, in spite of the functional role of the cytokine, genotype frequencies in CD patients are not different a from those observed in age-matched and 95- year-old healthy controls (Table 1).

ACKNOWLEDGMENTS

This work was supported by grants from the Ministry of Education, University and Re- search, ex60% to G.C., C.C., and D.L. D.N. and A.C. are Ph.D. students of the Pathobiology Ph.D. course directed by C.C., of Palermo Uni- versity. This work is in partial fulfillment of the requirement for the Ph.D.

As is well known, the most important mod- ification of the immune system in the senes- cence is the filling of the immunologic space with memory and effector cells as a conse- quence of exposure to a variety of antigens.10 The continuous attrition caused by clinical and subclinical infections, as well as the continuous exposure to other types of antigens (food, al- lergens), is likely responsible for chronic im- mune system activation and inflammation; and the immunosenescence and probably morbid- ity and mortality are accelerated in those sub- jects who are exposed to an extra burden of antigenic load.11 Celiac disease is characterized by a sustained inflammatory response, leading to intestinal mucosa atrophy and increased ex- posure of the CD patient to food antigens.12 On

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E-mail: dolio@unipa.it