COMP does not directly modify the expression of genes involved in cartilage homeostasis in contrast to several other cartilage matrix proteins.

OBJECTIVE: We investigated whether COMP may modify cartilage metabolism and play a role as an endogenous disease aggravating factor in OA. MATERIALS AND METHODS: Full-length and momomeric COMP was recombinantly expressed in human embryonic kidney cells and purified it via affinity chromatography. Purified COMP was used to stimulate either primary human chondrocytes or cartilage explants. Changes in the expression profiles of inflammatory genes, differentiation markers and growth factors were examined by immunoassay and by quantitative real-time reverse-transcription polymerase chain reaction. RESULTS: Incubation of primary human chondrocytes or cartilage explants in the presence of COMP did not induce statistically significant changes in the expression of IL-6, MMP1, MMP13, collagen I, collagen II, collagen X, TGF-ß1 and BMP-2. CONCLUSIONS: In contrast to collagen II and matrilin-3, COMP lacks the ability to trigger a proinflammatory response in chondrocytes, although it carries an RGD motif and can bind to integrins. COMP is a well-accepted biomarker for osteoarthritis but increased COMP levels do not necessarily correlate with inflammation.

Gonadal function and fertility in survivors after Hodgkin lymphoma treatment within the German Hodgkin Study Group HD13 to HD15 trials.

PURPOSE: To optimize fertility advice in patients with Hodgkin lymphoma (HL) before therapy and during survivorship, information on the impact of chemotherapy is needed. Therefore, we analyzed gonadal functions in survivors of HL. PATIENTS AND METHODS: Women younger than age 40 and men younger than 50 years at diagnosis in ongoing remission at least 1 year after therapy within the German Hodgkin Study Group HD13 to HD15 trials for early- and advanced-stage HL were included. Hormone parameters, menstrual cycle, symptoms of hypogonadism, and offspring were evaluated. RESULTS: A total of 1,323 (55%) of 2,412 contacted female and male survivors were evaluable for the current analysis (mean follow-up, 46 and 48 months, respectively). Follicle-stimulating hormone, anti-Müllerian hormone, and inhibin B levels correlated significantly with therapy intensity (P < .001). Low birth rates were observed in survivors after advanced-stage treatment within the observation time (women, 6.5%; men, 3.3%). Regular menstrual cycle was reported by more than 90% of female survivors of early-stage HL (recovery time mostly ≤ 12 months). After six to eight cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone, menstrual activity was strongly related to age (< v ≥ 30 years: 82% v 45%, respectively; P < .001; prolonged recovery time). Thirty-four percent of women age ≥ 30 years suffered severe menopausal symptoms (three- to four-fold more frequently than expected). In contrast, male survivors had mean levels of testosterone within the normal range and reported no increased symptoms of hypogonadism. CONCLUSION: The present analysis in a large group of survivors of HL provides well-grounded information on gonadal toxicity of currently used treatment regimens and allows risk-adapted fertility preservation and comprehensive support during therapy and follow-up.

Antibody response to the extracellular adherence protein (Eap) of Staphylococcus aureus in healthy and infected individuals.

The extracellular adherence protein (Eap) from Staphylococcus aureus has been suggested as a vaccine candidate and for therapeutic use due to its immunomodulating and antiangiogenic properties; however, little is known about anti-Eap antibodies in humans. We determined anti-Eap antibody titers by enzyme-linked immunosorbent assay and Western blot and measured serum samples from 92 patients with proven S. aureus infections and 93 healthy controls. The functionality of antibodies was assessed by a phagocytosis assay using Eap-coated fluorescent microspheres. Antibodies were detected in all human samples, but not in mice. Patients showed significantly higher titers than controls [immunoglobulin M (IgM), P=0.007; IgG, P<0.0001]. Patients with deep or severe infections showed higher titers than those with superficial or mild disease. Eap alone was sufficient to promote phagocytosis by peripheral blood mononuclear cell and granulocytes that was moderately enhanced in the presence of human serum, but no correlation was found with the levels of anti-Eap antibodies. Anti-Eap antibodies are prevalent in all tested humans and correlate with the severity of S. aureus infection; however, they do not seem to provide protection against invasive infections. Before considering Eap for therapy or as a vaccine candidate, further studies are warranted to assess the impact of the interference between Eap and its specific antibodies.