Implications of a clinically ignored site of acanthosis nigricans: the knuckles.

BACKGROUND: The clinical epidemiology of acanthosis nigricans (AN) has not been entirely studied. Most studies mention only its prevalence taking any "typical site" as a whole. These studies were carried out at different ages, races, anthropometries, and skin phototypes without analyzing the comparative clinical connotation of different sites. Furthermore, it has never been explored as a potential early expression of insulin resistance before it becomes clinically evident. The objective was to determine the prevalence and body distribution of AN in easy-access sites to physical examination in a Latin American youth population and its clinical implications as an early marker for obesity. DESIGN AND PATIENTS: We conducted a prospective, cross-sectional, observational study in 703 randomly selected students. Participants' mean age was 19.1±1.68 years. Overweight and obesity occurred in 23.6% and 6.8%, respectively. 3 observers blindly assessed neck, axillae, elbow and knuckles. RESULTS: AN was identified in any of the examined sites in 47.8% of the participants. Its prevalence increased from 41% to 86% from normal to obese anthropometric categories. AN occurred in 1-4 sites in 23.1%, 10.8%, 6.9% and 7.1% of cases, respectively. The knuckles was the site with the highest prevalence of AN as an overall group (31.3%) and in the normal (24.9%) and overweight body mass index (46.4%) categories and there was a higher prevalence in the cases above the median in the normal body mass index category. In the obese group, AN was slightly more common in the neck but all sites had a very similar high prevalence. CONCLUSION: AN occurs with a high prevalence in Latin American youths, and its prevalence is much higher in a "non-classical" and ignored location where it is very easy to detect during physical examination: the knuckles. It may also occur earlier in this location in the evolution to obesity. The presence of AN in the knuckles in any patient, even if they have a normal body mass index, might indicate the likelihood of an early clinical manifestation of insulin resistance and metabolic consequences.

Targeting and retention of HPV16 E7 to the endoplasmic reticulum enhances immune tumour protection.

The endoplasmic reticulum (ER) is where the major histocompatibility complex (MHC) class I molecules are loaded with epitopes to cause an immune cellular response. Most of the protein antigens are degraded in the cytoplasm to amino acids and few epitopes reach the ER. Antigen targeting of this organelle by Calreticulin (CRT) fusion avoids this degradation and enhances the immune response. We constructed a recombinant adenovirus to express the E7 antigen with an ER-targeting signal peptide (SP) plus an ER retention signal (KDEL sequence). In cell-culture experiments we demonstrated that this new E7 antigen, SP-E7-KDEL, targeted the ER. Infection of mice with this recombinant adenovirus that expresses SP-E7-KDEL showed interferon induction and tumour-protection response, similar to that provided by an adenovirus expressing the E7 antigen fused to CRT. This work demonstrated that just by adding a SP and the KDEL sequence, antigens can be targeted and retained in the ER with a consequent enhancement of immune response and tumour protection. These results will have significant clinical applications.