Self-limited autoimmune disease related to transient donor B cell activation in mice neonatally injected with semi-allogeneic F1 cells.

BALB/c mice injected at birth with 10(8) semi-allogeneic (C57BL/6 x BALB.IgHb)F1 spleen cells develop a lupus-like syndrome in which autoantibodies bear exclusively the donor allotype. We have analyzed the evolution of donor B cell chimerism and the autoimmune manifestations during the first year of life in these mice. Anti-DNA, -histone, and -cardiolipin IgG antibodies as well as circulating immune complexes appeared in the second week of life, reached the highest values around the sixth week, and then progressively dropped to normal values after the sixth month in most mice. The kinetics of the evolution of the autoimmune manifestations, as well as the kinetics of serum donor Ig allotype, were parallel to the kinetics of donor B cell chimerism, which was particularly prominent in the spleens in early weeks of life, and progressively decreased after remission of the autoimmune syndrome. Membrane-proliferative glomerulonephritis, which was followed as the more representative histological abnormality in this model, was particularly evident after 10 weeks of life, but disappeared by the end of the follow-up. Interestingly, when mice with a self-limited disease were re-injected with 10(8) F1 spleen cells i.v., a flare in the serological manifestations was observed. In these re-injected mice a predominance of anti-DNA, IgG1 antibodies bearing exclusively the donor allotype was also observed, as in the early weeks of life.(ABSTRACT TRUNCATED AT 250 WORDS)     

The Effect of Desensitization Protocols on Human Splenic B-Cell Populations In Vivo

Rituximab, intravenous immunoglobulin (IVIG) and rabbit antithymocyte globulin (rATG) all have been suggested to have an effect on antibody producing cells, however, supporting data are lacking. To assess the impact of these agents on splenic B‐cell populations in vivo, we retrospectively examined 25 spleens removed from patients treated with these agents as part of desensitization protocols in either ABO incompatible or positive crossmatch living donor kidney transplantation. These were compared to control (CTL) spleens removed for trauma. CTLs and spleens removed at transplant after multiple pretransplant plasmaphereses (PP) plus low‐dose IVIG showed similar large numbers of naïve B cells (CD20⁺ and CD79⁺), plasma cells (CD138⁺) and memory B cells (CD27⁺ cells). Adding rituximab to this PP/IVIG regimen reduced the number naïve B cells, but had no effect on memory or plasma cells. Combination treatment (PP/IVIG, rituximab and rATG) showed a trend toward the reduction of CD27⁺ cells, but again plasma cells were unchanged. We conclude that none of these protocols reduces splenic plasma cells in vivo. PP/low‐dose IVIG does not alter splenic B cells, but the addition of rituximab decreases mature B cells. Memory B cells may be affected by combination therapy including rATG and requires further study.     

An open-label efficacy pilot study with pimecrolimus cream 1% in adults with facial seborrhoeic dermatitis infected with HIV

BACKGROUND: Seborrhoeic dermatitis (SD) is a common dermatosis in human immunodeficiency virus (HIV)-positive patients, many of whom do not respond satisfactorily to conventional topical treatments such as corticosteroids and antifungals. OBJECTIVE: A pilot study to investigate the efficacy and tolerability of pimecrolimus cream 1% in HIV-positive patients with facial SD. METHODS: In a single-centre study, 21 HIV-infected patients with mild to severe SD were treated twice daily with pimecrolimus cream 1% for 14 days. Thereafter, treatment was discontinued and patients followed up for 5 weeks. Skin involvement at baseline and on days 7, 14, 21, 35 and 49 was assessed using a four-point clinical score and digital photography. MAIN OUTCOME MEASURES: Efficacy and safety of pimecrolimus cream 1% treatment and incidence of relapse in the follow-up phase. Results Marked improvement was seen in clinical parameters at day 7, with >or= 90% patients clear of symptoms at day 14. Relapse was observed at day 35 but signs were milder than at baseline. All patients responded to therapy, despite their immunological status. Pimecrolimus did not alter CD4(+) and CD8(+) T-cell counts or viral load during the treatment period. CONCLUSION: Pimecrolimus cream represents a new, effective therapeutic option for facial SD in HIV patients.     

Effect of elevated prolactin levels on the synthesis and release of catecholamines from the adrenal medulla in female rats

Recent evidence suggests that increased plasma prolactin (PRL) levels could be modifying the synthesis and release of catecholamines (CA) from the adrenal medulla. In order to study this possibility, female rats bearing an anterior pituitary gland, from a litter-mate donor, under the right kidney capsule since day 30 of life and their sham-operated controls were sacrificed by decapitation 45 days after the transplant operation. Plasma PRL and CA levels and CA content in the adrenal medulla were analyzed. A significant increase in plasma PRL levels was shown in grafted (22 +/- 2 micrograms/l) when compared to control rats (6 +/- 0.3 micrograms/l), together with a significant increase in plasma norepinephrine (NE) (4.2 +/- 1.1 micrograms/l vs. 1.7 +/- 0.7 micrograms/l) and epinephrine (E) (2.9 +/- 0.6 micrograms/l vs. 1.6 +/- 0.2 micrograms/l). Similar plasma dopamine (DA) levels were found in both groups (0.6 +/- 0.2 micrograms/l vs. 0.8 +/- 0.3 micrograms/l). An increase in adrenal DA content (29.1 +/- 6.8 ng/mg protein), together with a decrease in NE (33.3 +/- 6.8 ng/mg protein) and E content (65.9 +/- 11.8 ng/mg protein) was detected in grafted as compared to control rats (DA: 12.0 +/- 3.6 ng/mg protein; NE: 79.3 +/- 22.1 ng/mg protein; E: 184.2 +/- 39.2 ng/mg protein). We can conclude from these data that the elevation of circulating PRL levels induced by a pituitary graft is able to increase the synthesis and release of CA from the adrenal medulla in female rats.     

The use of the face-hand test to screen for organic brain syndromes. A pilot study

A reduced version of the Face-Hand Test (FHT), the FHT-R, was applied to a random sample of 91 elderly subjects living in the community (S. Paulo-Brazil), to study the instrument's ability to detect Organic Brain Syndrome (OBS). The scores of the FHT-R test were then compared with a psychiatric assessment using the Clinical Interview Schedule. Five persons were regarded as OBS "cases" and 86 as OBS "non cases". At the cut-off point 0/1 the validity coefficients were as follows: Sensitivity 60%, Specificity 94%, Positive Predictive Value 38%, Negative Predictive Value 98% and Overall Misclassification Rate 8%. The usefulness of this clinical test to screen for OBS in epidemiological surveys is discussed.     

Impaired Recovery of CD4+ Cell Counts Following Highly Active Antiretroviral Therapy in Drug-Naïve Patients Coinfected with Human Immunodeficiency Virus and Hepatitis C Virus

Coinfection with the human immunodeficiency virus (HIV) and the hepatitis C virus (HCV) is highly prevalent in southern Europe. However, there are few and contradictory data about the effect of HCV carriage on the response to highly active antiretroviral therapy (HAART). In this study, the recovery of CD4+ T cells following HAART among antiretroviral-naïve patients seropositive for HIV with and without HCV coinfection was investigated. Two hundred one HIV-infected patients without previous exposure to antiretroviral drugs were included in the study. HCV coinfection was detected in 123 (61%) patients. The time to recover 200 CD4+ cells/µl was longer in the HCV-positive group (P<0.001). In a Cox model, HCV infection and lack of persistent HIV viremia (defined as <200 copies/ml) were associated with the time to recover 200 CD4+ cells/µl. The mean increase in CD4+ cell counts was lower in the HCV-positive group during the first year of therapy. HIV/HCV-coinfected patients naïve for antiretroviral therapy show a delayed recovery of CD4+ cell counts after starting HAART.