Role of three quantitatively dominant endogenous peptides from HLA-DRB1*0401 molecules in class II specific alloreactivity.

Alloreactivity remains an important barrier to organ transplantation and is caused by T cell recognition of foreign histocompatibility antigens (HAg) in two ways: (1) indirect recognition, in which processed HAg peptides are presented by self MHC like any other foreign antigen, and (2) direct recognition, where the foreign MHC itself is recognized in contravention of the T cell recognition rule of self restriction. Whereas the role of endogenous peptides in direct MHC class I specific recognition is now established, their role in class II specific direct alloreactivity remains controversial, since no defined endogenous peptide has been shown to be required for alloreactivity. That mutations resulting in defective antigen processing impair class II specific allostimulation, however, suggests that the endogenous pathway is important for class II as well as class I alloreactivity. We attempted to establish the importance of endogenous peptides for alloreactivity by identifying common sequences of peptides bound by DR molecules of an HLA-DRB1*0401 homozygous B cell line. Peptides corresponding to three of these (calreticulin, HLA class I and an unidentified molecule) were used to restimulate established allospecific HLA-Dw4 reactive T cell clones, as well as to sensitize allogeneic T cells de novo in vitro. Xenogeneic chinese hamster ovary (CHO) cells coexpressing the relevant DR allele together with CD80 were used as antigen presenting cells. The role of CD80 could be determined on these cells because (1) they are xenogeneic and (2) they do not express B7 family members bound by CTLA-4Ig.(ABSTRACT TRUNCATED AT 250 WORDS)

[Symptom-oriented follow-up of early breast cancer compared to intensive surveillance. Results of a prospective multicentre study: update and 10-year overall survival]. / Symptomorientierte Nachsorge nach Mammakarzinom im Vergleich zur intensiv-apparativen Nachsorge. Ergebnisse einer prospektiven multizentrischen Studie: Update und 10-Jahres-Überlebenszeit.

BACKGROUND AND OBJECTIVE: In a prospective, non-randomised, multicentre cohort study we compared intensive surveillance to symptom-oriented control in the follow-up of patients with early breast cancer after curative surgical treatment. Five-year overall survival had shown that symptom-oriented follow-up was not inferior to intensive control. However, a more intensive, instrumental based follow-up is still claimed by many patients and their physicians. In this context the recent data of 10-year overall survival (OS) are reported. PATIENTS AND METHODS: In the prospective, non-randomised, multicentre cohort study carried out between 1995 and 2000, 244 patients underwent an intensive follow-up (scheduled laboratory tests including CEA and CA 15-3, chest X-rays and liver ultrasound). 426 patients were monitored in a symptom-oriented manner (additional tests only in the case of symptoms indicating possible recurrence). Mammography, structured histories and physical examinations were done regularly in both groups. RESULTS: In the clinical follow-up group, 90 deaths (21.2 %) were observed with an estimated 10-year overall survival rate of 83.0 % (95 % CI 79.1 -86.3 %).  In the intensive follow-up group, 59 deaths (24.2 %) were observed with an estimated 10-year overall survival rate of 78.5 % (95 % CI 72.6 -83.2 %). The Cox proportional hazards model for OS includes the variables follow-up form, stage of primary tumor and lymph nodes, hormone receptor status, grading and age at diagnosis. This model resulted in a hazard ratio of 1.10 (95 % CI 0.78-1.54) for the follow-up protocol (intensive vs. clinical). Welleks' test for non-inferiority showed that clinical follow-up is not inferior in comparison to intensive follow-up (p < 0.05) for a non-inferiority limit of + 7 % at 10-years. CONCLUSION: This analysis of 10-year overall survival of patients with early breast cancer after curative primary treatment confirms that follow-up without regular imaging and laboratory tests is not inferior in the sense of a relevant higher mortality. To what extent new concepts in the treatment of breast cancer have any influence on follow-up care has to be examined in further studies.