Biomedical subjects

Michael Hertl

Publications and source records attributed to Michael Hertl.

25 records · Page 2Linked to original sources

PubMed2003

T-cellular autoimmunity against desmogleins in pemphigus, an autoantibody-mediated bullous disorder of the skin.

Pemphigus encompasses a group of life-threatening blistering diseases of the skin in which loss of adhesion between keratinocytes is caused by autoantibodies (Ab) against desmogleins (Dsg) 1 and 3. There is major interest in characterizing autoreactive T cells that are presumably critical for the induction and regulation of Ab production. In a recent study, peripheral Dsg3-reactive T helper (Th) cells from patients with acute onset, chronic active and remittent pemphigus vulgaris (PV) were quantitated by MACS secretion assay. Dsg3-reactive Th2 cells were detected at similar frequencies in all the studied PV patients while the number of autoreactive Th1 cells exceeded those of the Th2 cells in chronic active PV. Noteworthy, healthy carriers of the PV-associated HLA class II alleles, DRbeta1*0402 and DQbeta1*0503, exhibited exclusively Th1 reactivity against Dsg3. The titers of Dsg3-reactive IgG were directly related to the ratio of autoreactive Th1/Th2 cells. Moreover, T cell recognition of Dsg3 was restricted by these HLA class II alleles. These findings strongly suggest that (1) Dsg3-reactive Th2 cells are restricted to PV, (2) distinct HLA class II alleles are critical for T cell recognition of Dsg3, and (3) Ab production is associated with both, Th1 and Th2 cells.

Autoantibodies↗

PubMed2003

[The use of high dose intravenous immunoglobulins in dermatology].

High dose intravenous immunoglobulins (IVIG) are important agents in the treatment of numerous diseases in rheumatology and dermatology. Because the diseases treated with IVIG are rare, their use is mostly not based on controlled randomized trials. Since the high costs of therapy often prohibit the use of IVIG as first line therapy and as there are no guidelines on the use of IVIG in dermatologic diseases, a consensus conference was held in Wiesbaden, Germany, to address these issues. This manuscript documents the expert consensus on the use of IVIG in dermatology and reflects current clinical practice. It should be a guideline for the practitioner for the use of IVIG in dermatologic diseases.

Dermatology↗

PubMed2003

[Therapeutic application of TNF-alpha inhibitors infliximab and etanercept in inflammatory skin disorders].

BACKGROUND: The treatment of inflammatory skin diseases is at present often empirical as causal therapeutic approaches are not available because of incomplete knowledge of the immune pathogenesis. The current therapeutic approaches can induce remission, but often produce undesirable side effects. On the basis of experience gained in cytokine modulation therapy of chronic inflammatory diseases such as rheumatoid arthritis and psoriasis, the use of TNF-alpha inhibitors could represent a further, more specific and effective therapeutic option for other selected inflammatory skin diseases. PATIENTS AND METHODS: The current status of the therapeutic effect of anti-TNF-alpha blockers is discussed based on our own observations and a review of the current literature. Potential undesirable side effects and possible contraindications for this therapy are also considered. RESULTS AND CONCLUSIONS: Based on the recent findings, the use of TNF-alpha blockers seems to be promising in the treatment of therapy-resistant inflammatory dermatoses. At present, guidelines for indications and contraindications for anti-TNF-alpha treatment of inflammatory skin disorders do not exist. Such guidelines are necessary to improve the efficacy of anticytokine treatment and to reduce side effects.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2002

Risk factors for lethal outcome in patients with bullous pemphigoid: low serum albumin level, high dosage of glucocorticosteroids, and old age.

BACKGROUND: Although bullous pemphigoid (BP) is the most frequent autoimmune bullous disease and is associated with a considerable case-fatality rate, little is known about factors that influence its prognosis. OBJECTIVE: To identify prognostic factors for lethal outcome in the first year after the initial hospitalization in patients with BP. DESIGN: A multicenter retrospective cohort study. SETTING: Seven dermatologic university hospitals in Germany. PARTICIPANTS: A total of 369 patients diagnosed as having BP between January 1, 1987, and December 31, 1997. STATISTICS: Univariate (Kaplan-Meier) and multivariate (Cox regression) analysis. RESULTS: Of the 369 patients with BP, 209 (57%) died, 106 (29%) within the first year after hospitalization. Fifty-four percent were women. The mean +/- SD age at entry was 77.3 +/- 11.1 years. The patients with BP were followed up to 10.5 years, with a median time of 1.8 years to death or interview (25th and 75th quartiles, 0.5 and 4.0 years). The major risk factors for lethal outcome in the first year after hospitalization were an increased age, with a multivariate risk estimate of 3.2 (95% confidence interval [CI], 1.9-5.2) for age greater than 80.4 years (median); a daily glucocorticosteroid dosage of more than 37 mg (75th quartile) at discharge, with a multivariate risk estimate of 2.5 (95% CI, 1.5-4.3); serum albumin levels of 3.6 g/dL or less (25th quartile), with a multivariate risk estimate of 2.6 (95% CI, 1.5-4.4); and an erythrocyte sedimentation rate greater than 30 mm/h (75th quartile), with a multivariate risk estimate of 1.7 (95% CI, 1.1-2.8). CONCLUSIONS: There is a considerable case-fatality rate in patients with BP. Older patients who require a higher dosage of oral glucocorticosteroids at hospital discharge and who have low serum albumin levels are at greater risk of death within the first year after hospitalization. These prognostic factors should be considered in the care of patients with BP as well as in the design of future clinical trials.

Aged↗

PubMed2002

Severity and phenotype of bullous pemphigoid relate to autoantibody profile against the NH2- and COOH-terminal regions of the BP180 ectodomain.

Bullous pemphigoid, the most common autoimmune subepidermal bullous disorder, is associated with autoantibodies targeting antigenic sites clustered within the extracellular domain of BP180. To investigate epitope and subclass specificity of autoantibodies in bullous pemphigoid, we developed an enzyme-linked immunosorbent assay utilizing baculovirus-expressed recombinant forms of the NH2- and COOH-terminal regions of the extracellular domain of BP180 and examined sera obtained from patients with active bullous pemphigoid (n=116) and controls (n=100). Ninety-three (80%) and 54 (47%) of the 116 bullous pemphigoid sera recognized the NH2- and COOH-terminal regions, respectively, of the extracellular domain of BP180. Detailed analysis demonstrates that (i) this novel enzyme-linked immunosorbent assay is highly specific (98%) and sensitive (93%) as 108 of 116 bullous pemphigoid sera reacted with at least one of the baculovirus-derived recombinants, (ii) in active bullous pemphigoid, autoantibodies against the NH2-terminus of the extracellular domain of BP180 were predominantly of the IgG1 class, whereas a dual IgG1 and IgG4 response to this region was related to a more severe skin involvement, (iii) autoreactivity against both the NH2- and COOH-terminal regions was more frequently detected in patients with mucosal lesions, and (iv) levels of IgG (and IgG1) against the NH2-terminal, but not against the COOH-terminal portion of the extracellular domain of BP180, reflected disease severity indicating that autoantibodies against the NH2-terminus are critical in the pathogenesis of bullous pemphigoid. In conclusion, this novel enzyme-linked immunosorbent assay represents a highly sensitive and specific assay for rapid diagnosis of bullous pemphigoid and related disorders and may provide predictive parameters for the management of bullous pemphigoid patients.

Autoantibodies↗

PubMed2002

Pemphigus vulgaris localized to the nose and cheeks.

Pemphigus vulgaris is an autoimmune blistering disease characterized by disseminated bullae and erosions of the mucosal surfaces and skin. Cases of pemphigus vulgaris with localized lesions on glabrous skin have been reported, and most of them have been attributed to the Koebner phenomenon. Lesions limited to the nose have mostly been described in pemphigus foliaceus, but the nose has also been the initial site of pemphigus vulgaris in a few patients. We report 4 cases of localized pemphigus vulgaris: one case with lesions limited to the nose and cheeks and 3 cases with isolated lesions on the nose. Recurrent episodes in these patients also occurred on the nose. None of them showed mucosal involvement or dissemination during a follow-up period of 2 to 9 years. Three patients had autoantibodies against desmoglein-3 as detected by immunoblot. In the other patient, antibodies against desmoglein-3 were detected by enzyme-linked immunosorbent assay. These localized lesions may represent a subgroup of pemphigus vulgaris or a period of limited activity during this chronic disease.

Adult↗

PubMedDate not supplied

Delayed response of oral pemphigus vulgaris to rituximab treatment.

Rituximab is a monoclonal antibody directed against the CD20 antigen of B cells, which has been developed for the treatment of lymphomas and has been successfully used in the treatment of recalcitrant pemphigus vulgaris. Here, we report on a 26-year-old patient with an 18 month history of pemphigus vulgaris of the oral mucosa where treatment with rituximab led to a delayed but sustained therapeutic response. This case is of interest since most of the previous reports have described a more rapid clinical improvement of refractory pemphigus by rituximab treatment. The delayed clinical response to rituximab of the present case may be explained by the persistence of long-lived plasma cells that continued to produce pathogenic autoantibodies against desmoglein 3.

Adult↗