Biomedical subjects

Rolf Hoffmann

Publications and source records attributed to Rolf Hoffmann.

23 records · Page 2Linked to original sources

PubMed2002

Transient CD44 variant isoform expression and reduction in CD4(+)/CD25(+) regulatory T cells in C3H/HeJ mice with alopecia areata.

Alopecia areata, an autoimmune disease affecting anagen stage hair follicles, can be induced by grafting spontaneous alopecia areata affected skin to normal-haired C3H/HeJ mice. As the onset of alopecia areata can be significantly retarded by anti-CD44 variant isoform 10 treatment, it was interesting to explore the underlying disease mechanism. Two weeks after transplanting alopecia areata affected skin, expression of CD44 variant isoforms 3, 6, 7, and 10 was strikingly upregulated as compared with sham-grafted mice. By 6 wk after grafting, CD44 variant isoform levels had returned to normal, whereas in draining lymph nodes, CD44 variant isoform expression was slightly decreased. Leukocytes in the skin of mice with chronic alopecia areata expressed a hematopoietic isoform of CD44 and CD44 variant isoform 6 at an elevated level, but CD44 variant isoform 3 expression was reduced. Cytokine expression in leukocytes of chronic alopecia areata affected skin was higher than in normal-haired controls. Cytokine expression also increased postsurgery in sham and alopecia areata grafted mice, but remained elevated only in mice receiving alopecia areata affected skin. Finally, from the skin of mice with chronic alopecia areata and of mice transplanted with alopecia areata affected skin, an increased number of CD4(+) and CD8(+) cells, but a strongly decreased number of CD4(+)/CD25(+) regulatory T cells was recovered. Thus, expression of CD44 variant isoforms is important for the migration of leukocytes during the initial period of alopecia areata. CD44, however, is apparently not involved in the maintenance of the disease state, which is characterized by high cytokine expression levels, an increased number of CD4(+) and CD8+ cells, but a low level of CD4(+)/CD25(+) suppressor cells.

Alopecia Areata↗

PubMed2002

Resistance to alopecia areata in C3H/HeJ mice is associated with increased expression of regulatory cytokines and a failure to recruit CD4+ and CD8+ cells.

Grafting alopecia areata affected C3H/HeJ mouse skin to littermates induces alopecia areata, but high dietary soy oil reduces alopecia areata susceptibility. Alopecia areata affected and resistant mice were characterized to evaluate possible mechanisms involved in alopecia areata resistance. Of 44 mice that received alopecia areata affected skin grafts but failed to develop alopecia areata, only two of 22 receiving further alopecia areata affected skin grafts developed alopecia areata, whereas 39 of 44 controls developed alopecia areata. Alopecia areata affected skin contained increased numbers of CD4+ and CD8+ cells, increases in pro inflammatory T helper 1 and T helper 2 type cytokines, and upregulation of CD28, CD40L, and their ligands. In draining lymph nodes, a relatively high number of antigen-presenting cells was recovered, whereas several CD44v variants were downregulated. In contrast, alopecia areata resistant mouse skin did not display increased numbers of CD4+ and CD8+ cells, whereas counter-regulatory cytokines interleukins 4 and 10 were upregulated. High expression of CD28, CD80, CD86, CD40, CTLA4, CD44v variants, and FasL occurred in alopecia areata resistant mouse spleens. In vitro, lymph node cells of susceptible and resistant mice responded equally to a mitogenic stimulus, but only lymph node cells from alopecia areata affected mice displayed an increased response with T cell receptor stimulation via anti-CD3 cross-linking. These results suggest alopecia areata is a cell-mediated autoimmune disease, but alopecia areata affected skin graft hosts may resist alopecia areata onset through active counter-regulatory mechanisms. Because alopecia areata resistant mice showed unimpaired responsiveness and a transient inflammatory response towards the graft, it is suggested that alopecia areata develops as a consequence of an inappropriate immune response regulation.

Alopecia Areata↗

PubMed2002

Multiple eruptive dermatofibromas: a review of the literature.

In this review we summarize the characteristic features of multiple eruptive dermatofibromas based on an analysis of cases in the literature. Many researchers have reported multiple eruptive dermatofibromas diagnosed using the definition of "multiple" as the presence of at least 15 lesions. However, this criterion is arbitrarily chosen and might not be entirely valid for all cases. A more precise definition may include the eruption of several multiple eruptive dermatofibromas reported within a short period of time. Because more than half of the patients with multiple eruptive dermatofibromas have underlying diseases, and more than 80% of the underlying diseases are immune-mediated, multiple eruptive dermatofibromas could possiblv be considered as a partial manifestation of an immune-mediated disease. This underscores the possibility of early diagnosis of immune-mediated diseases in patients with multiple eruptive dermatofibromas.

Adolescent↗

PubMedDate not supplied

Diphencyprone immunotherapy alters anti-hair follicle antibody status in patients with alopecia areata.

Alopecia areata (AA) is a relatively common reversible hair loss disorder usually manifesting as patchy areas of complete hair loss on the scalp and other body parts that can progress to complete loss of all body hair. This condition is now generally assumed to be an autoimmune disease with the hair follicle (HF) as the principal target tissue. AA may be passively transferred by T cells and there is some evidence that serum IgG may also disturb hair cycling. Here, we examine whether the status of anti-HF antibody reactivity is altered during hair regrowth associated with topical immunotherapy using the contact sensitizer diphencyprone. Eleven patients with severe AA of the scalp were treated with diphencyprone on one side of the scalp and serum was obtained from each patient before the start of therapy, after unilateral hair regrowth, during continuing hair regrowth and in some cases after complete and sustained regrowth. The presence and titer of circulating antibodies to HF was assessed by indirect immunofluorescence and immunoblotting analysis. A striking reduction was detected in both the titer and range of HF components/antigens targeted by anti-hair follicle IgG antibodies in those patients that exhibited complete and sustained hair regrowth after DCP-treatment. By contrast, unilateral hair regrowth was associated with no change, or even an increase, in anti-HF antibody titer and reactivity. Therefore we can conclude that the down-regulation of antibody reactivity is likely to be a result rather than the cause of hair regrowth induction by topical immunotherapy. As this immunotherapy is associated with a reduction in the titer/pattern of anti-HF antibodies, these may hold the key to the identity of the HF antigen targets in AA. Moreover, the presence/titer of anti-HF antibodies may be a marker of clinical disease activity or opportunity for spontaneous regrowth.

Administration, Topical↗

PubMedDate not supplied

Genital Paget's disease in a man.

Pagetoid cells are large intraepidermal cells which spread intraepidermally. We report a 67-year old Caucasian male, who presented for the first time in 1993 with a long-standing pruritic lesion at the scrotum. He was treated for several years by antiinflammatory ointments. Only in July 2003 was a biopsy taken for the first time. The histopathological evaluation revealed the diagnosis of an extramammary Paget's disease (EMPD). Pagetoid cells are large intraepidermal cells with a large nucleus and ample cytoplasm. EMPD consists of primary malignant cells of epidermal origin, but in rare cases, pagetoid cells may also originate from carcinomas with epidermotropic growth. EMPD is a slowly progressing disease, but invading and metastasing tumors may also develop. Considering the good prognosis with long-term survival, nonsurgical modalities should be considered as primary treatment for noninvasive EMPD.

Administration, Topical↗