Genomic instability in scleroderma.

Scleroderma is an enigmatic rheumatic disorder of uncertain etio-pathogenesis. Cancer has an approximately two-fold higher incidence in scleroderma patients than in the general population. There are preliminary data of acquired genetic damage in scleroderma but the significance of these observations are uncertain. To determine somatic mutation frequency at the glycophorin-A (GPA) locus in patients with limited and diffuse cutaneous scleroderma. The GPA assay measures the total somatic mutation frequency (Vf), composed of gene inactivating mutations (NO) and mutations arising from mitotic recombination (NN) in individuals heterozygous for the GPA MN blood group. Mutation frequency was determined using a validated GPA flow cytometric assay using fluorescent labeled monoclonal antibodies specific for the GPA blood groups M and N. This assay detects and enumerates progeny of red blood cell (rbc) precursor cells which have acquired genetic damage resulting in a loss of expression of one of the GPA alleles. It was found that patients with scleroderma (n = 23) had significantly elevated Vf as compared with young healthy controls (p < 0.001) and elderly controls (p = 0.03). Patients with diffuse scleroderma had higher mean Vf as compared with limited scleroderma (p = 0.055). In comparison with controls, patients with scleroderma exhibit a higher proportion of mitotic recombinant mutations than inactivating mutations (p < 0.002). There was no correlation between Vf and disease duration, age at onset or autoantibody status. We have documented evidence of acquired genetic damage at the GPA locus in scleroderma. Evidence of acquired genetic damage in this disorder may be importance in explaining both the etio-pathogenesis of scleroderma and the association of scleroderma with cancer.

Hipersensibilidad retardada a antígenos de evocación: valores normales en adultos jóvenes chilenos / Delayed hypersensitivity to evocation antigens: standard values in chilean young adults

Delayed hypersensitivity skin test are widely accepted as in vivo measure of cellular immunity. Since genetic and environmental factors may affect these tests, each population must establish its own normal values. The aim of this work was to study delayed hypersensitivity in chilean normal young adults. We studied the response to 8 antigens using the Multitest CMI (Rhodia Merieux) in 50 students (22 females, 28 males), aged 18 to 25 years old. Skin tests were read at 24, 48 and 72 hours. At 48 h, 60 percent of women responded to 3 and 68 percent of men to 4 antigens. A mean response to 3.6 antigens was observed. Total score in men and women were 19.5ñ7.3 and 12.2ñ6.5 mm respectively (p<0.05). These figures are different from these published abroad and confirm the need for national standards