Increased Frequency of HLA-DR2 in Patients with Autoantibodies to Epidermolysis Bullosa Acquisita Antigen: Evidence that the Expression of Autoimmunity to Type VII Collagen Is HLA Class II Allele Associated

Epidermolysis bullosa acquisita (EBA) is a chronic blistering disease characterized by circulating and tissue bound IgG auto-antibodies to the basement membrane zone (BMZ) of stratified squamous epithelium. Recent studies have shown that antibodies recognize epitopes present in the noncollagenous carboxyl-terminal domain of type VII collagen, a BMZ matrix protein. Antibodies with identical specificity also have been detected in patients with the rare blistering disease, bullous systemic lupus erythematosus (bullous SLE), suggesting EBA and bullous SLE are immunologically related diseases. In this study we determined the major histo-compatibility antigen types of 29 EBA patients and 6 patients with bullous SLE. Analysis of the results showed HLA-DR2 was significantly increased in both black EBA patients, P = 0.013 (corrected, RR = 4.8) and whit EBA patients, P = 0.0008 (corrected, RR = 13.1). Five of the six bullous SLE patients also were positive for the DR2 antigen, P = 0.009. These results show the expression of autoimmunity to type VII collagen is HLA class II allele associated and that EBA and bullous SLE are immunogentically related diseases

The relationship of agonistic and affiliative behavior patterns to cellular immune function among cynomolgus monkeys (Macaca fascicularis) living in unstable social groups

Considerable recent interest has focused on the possibility that behavioral factors may influence immune competence, and hence, potentially, patterns of disease. We report here the relationship between the aggressive and affiliative behavior and the cellular immune responses of 30 adult male cynomolgus monkeys (Macaca fascicularis) living in small (n = 5) social groups whose members were periodically redistributed over 26 months. Animals also were subjected to behavioral observation, allowing them to be categorized as either high or low in aggressiveness and affiliation. At the end of the 26 months, lymphocyte proliferation tests were performed on blood samples from all monkeys, using both concanavalin A (ConA) and phytohemagglutinin (PHA) in concentrations of 1, 5, and 10 ug/ml. Two-by-two (Aggressiveness [high, low] X Affiliation [high, low]) analyses of variance performed on these data showed lymphocyte proliferation in response to both ConA and PHA to be greatest (at 1 ug/ml) among highly affiliative animals, albeit only if they were also low in aggressiveness (ConA: Affiliation x Aggression, P P P < 0.05). These results indicate that immune competence may be enhanced among monkeys which, in response to a disrupted social environment, spend large amounts of time in affiliation with other animals. Social status, a phenomenon known to influence many aspects of nonhuman primate physiology, was unassociated with nonspecific lymphocyte blastogenesis or natural killer cell activity in this experiment.</p

Effects of social reorganization on cellular immunity in male cynomolgus monkeys

Exposure to acute stressors has been shown to impair cellular immunity in human beings and other animal species. Comparatively little is known, however, about the effects of long-term stressors on immune function and how individual behavioral characteristics may mediate differences in immune function and clinical disease susceptibility. To determine the effects of social stress on cellular immunity and reactivation of a latent herpesvirus, 20 Herpes B virus-positive male cynomolgus monkeys were exposed to four periodic reorganizations of social group memberships over 5 months. Observations were made to categorize individuals as high or low in expression of aggressive, fearful, and affiliative behaviors. Complete blood counts, lymphocyte proliferation tests, and natural killer cell cytotoxicity assays were performed immediately before and 4 days after reorganizations. Herpesvirus-specific immunoglobulin G antibody levels were measured, and oral and conjunctival swabs were cultured for virus. Reorganization was associated with increased lymphocyte counts (P = 0.0009) and decreased lymphocyte proliferation in response to phytohemagglutinin (P < 0.005), particularly among monkeys showing high levels of fear (P = 0.0137). High-aggressive monkeys showed lower baseline natural killer cell activity (P = 0.0013) and higher lymphocyte counts (P = 0.013) than low-aggressive monkeys. Herpesvirus antibody titers decreased over time (P < 0.004) and no positive virus cultures were obtained. Measures of cellular immunity and behavior were unrelated to virus-specific antibody titers. These results suggest that repeated exposure to a social stressor alters several measures of cellular immunity, and that some of these changes may be predicted by individual differences in agonistic behavior. In contrast to human studies, the results suggest that some psychological stressors may not cause reactivation of a common herpesvirus in this species