Apoptosis of naive CD4+ T-cells from HIV-infected patients with poor immune response to HAART is enhanced in vitro by steroid

OBJECTIVE: Because the absence of immune restoration in HIV-infected patients efficiently treated by highly active antiretroviral therapy (HAART) may be due to excessive immune activation, we prospectively studied the effect of hydrocortisone on T-cell apoptosis in a cohort of patients with satisfactory virologic response. METHODS: Apoptosis of T-cell subsets including na?ve CD45RA(+)CD4+ T-cells was determined at baseline and at months 1 and 3 after initiation of HAART. A satisfactory immune response was defined as an increase >100/microL CD4+ T-cells at month 3 compared to baseline. RESULTS: Twenty out of 63 patients showed undetectable viral load at month 3, among whom eight exhibited a satisfactory immune response. Down-regulation spontaneous CD4+T-cell apoptosis was significant in the group of patients with a satisfactory immune response compared to the other patients. However, hydrocortisone up-regulated apoptosis of na?ve CD4+ CD45RA+ T-cells, specifically in group of patients with poor immune response, whatever the time point considered: percentage of apoptotic CD4 T-cells was 16+/-16% without hydrocortisone and 22+/-22% with hydrocortisone at month 1, and respectively, 10+/-9 and 17+/-15% at month 3 (P < 0.05) Hydrocortisone had no impact on CD8+ T-cell apoptosis, whatever the considered group. CONCLUSION: Our results suggest to not use steroid therapy as adjuvant immunotherapy in patients with less than optimal immunologic response to HAART.     

Anti-TNF alpha monoclonal antibodies (infliximab) and tuberculosis: apropos of 3 cases

INTRODUCTION: Monoclonal TNF alpha antibodies are a new treatment of severe rheumatoid arthritis. One of the possible side effects is the appearance of opportunistic infections. We report here on three cases of disseminated tuberculosis observed in patients undergoing treatment with infliximab. EXEGESIS: A 45-year-old woman, treated with infliximab, was hospitalised after five infusions for fever and dyspnoea. The exams showed pulmonary and peritoneal tuberculosis. The second case is a 75-year-old woman whose symptoms were fever, cough and cervical adenopathy after three infliximab infusions. Diagnosis was disseminated tuberculosis. The third case is a 59-year-old man who was hospitalised for an infectious syndrome with dyspnoea, after two infliximab infusions. We discovered pulmonary tuberculosis. CONCLUSION: These three cases added to the 68 cases of tuberculosis registered with the treatment of infliximab. This confirms the risk of severe opportunist infectious side effects. TNF alpha is a cytokine which has anti-infectious properties. These tuberculoses are severe and generalized. It is recommended to search for an active or latent tuberculosis before beginning treatment with infliximab, and to check these patients frequently.     

Efficacité à moyen terme de l’autogreffe de cellules souches hématopoïétiques périphériques sur la polyneuropathie du syndrome POEMS : expérience chez 5 cas

Introduction

POEMS syndrome (polyneuropathy, organomegaly, endocrynopathy, M-protein, and skin changes) is a rare multisystem disease associated with plasma cell dyscrasia. The efficacy of autologous peripheral blood stem cell transplantation (auto-PBSCT) reported in case series has been mainly based on hematologic criteria and clinical recovery of peripheral neuropathy dysfunctions but has not been specifically evaluated. This retrospective study aimed to analyze the efficacy of auto-PBSCT on disability and electrophysiological patterns in patients with POEMS syndrome.

Methods

Five patients presenting with POEMS syndrome received auto-PBSCT. Disability was evaluated before treatment and at 6 and 12 months using the Overall Neuropathy Limitation Scale (ONLS) and MRC sumscore of 28 muscles. Nerve conduction studies were performed before and one year after treatment, on median, ulnar, fibular and tibial nerves.

Results

Mean age was 60.6 years (49–70). Disease duration between first symptoms and auto-PBSCT was 15.4 months (2–33). Before auto-PBSCT, mean ONLS score was 4.2 (1–10) and mean MRC sumscore 115.8/140 (74–140). At M6, mean ONLS score decreased and mean MRC sumscore increased; both were improved in all patients at M12: mean ONLS score 3 (range 0–8) at M6 and 2.2 (range 0–7) at M12; mean MRC sumscore 118/140 (77–140) at M6 and 122.4/140 (80–140) at M12. Significant recovery in electrophysiological patterns was observed in all patients on ulnar and median nerves: before-after treatment differences were observed for motor conduction velocities (34.41 vs. 45.47 m/s; P < 0.001), distal CMAP amplitudes (5.04 vs. 5.96 mV; P = 0.004), and sensory conduction velocities (43.20 vs. 49.20 m/s; P = 0.001). Distal CMAP amplitude remained low in fibular and tibial nerves (0.41 vs. 0.17 mV).

Conclusions

Clinical and electrophysiological improvement is obvious in POEMS syndrome peripheral neuropathy within one year after treatment with auto-PBSCT, undoubtedly resulting from extensive remyelinisation and axonal regeneration. Further studies are required to examine long-term outcome in patients with POEMS syndrome given auto-PBSCT.     

Heterogeneity of t(4;14) in multiple myeloma. Long-term follow-up of 100 cases treated with tandem transplantation in IFM99 trials.

One hundred de novo multiple myeloma patients with t(4;14) treated with double intensive therapy according to IFM99 protocols were retrospectively analyzed. The median overall survival (OS) and event-free survival (EFS) were 41.4 and 21 months, respectively, as compared to 65 and 37 for patients included in the IFM99 trials without t(4;14) (P<10(-7)). We identified a subgroup of patients presenting at diagnosis with both low beta(2)-microglobulin <4 mg/l and high hemoglobin (Hb) >/=10 g/l (46% of the cases) with a median OS of 54.6 months and a median EFS of 26 months, respectively, which benefits from high-dose therapy (HDT); conversely patients with one or both adverse prognostic factor (high beta(2)-microglobulin and/or low Hb) had a poor outcome. The achievement of either complete response or very good partial response after HDT was also a powerful independent prognostic factor for both OS and EFS.     

Positive HIV (human immunodeficiency virus) serology in the pregnant woman: current data on its management. Apropos of a continuous series of 56 cases

56 cases of pregnant women with a positive HIV serology were reported in 20 months at the Maternity of the Nice Hospital Center. In 10 cases, there were clinical signs of the disease (9 ARC-Syndrome, one case of AIDS). The predisposing factor was most of the time drug addiction, 53 cases (94.5%) and one case occurred after a blood transfusion. In the majority of the cases (52%) the pregnancy was pursued because of the late term or the patient's decision. A therapeutic abortion was performed in 12 instances (25%) and an interruption before 12 weeks of amenorrhea in 15 cases. 24 women delivered. The obstetrical complications were frequent with especially a fetal death in utero, five premature deliveries and fifteen hypotrophies. A severe infectious complication (septicemia, pneumopathy secondary to Pneumocystis carinii) was observed in 9 cases, a marked thrombopenia causing profuse post-partum haemorrhages in one case. Finally, one woman died 35 days after delivery. The study of the consequences on the child is incomplete because of insufficient follow-up: all children were sero-positive at birth and among thirteen children aged between 12 to 20 months, there were one death, one AIDS syndrome, 4 ARC-syndrome, 4 sero-positive and 3 sero-negative. The notion of HIV sero-positivity in a pregnant woman presents serious problems for the obstetrician. Decompensation of the disease during the pregnancy is uncertain but it is now confirmed that the child is affected, and this is a well established fact. These important consequences lead to propose, at this time a therapeutic interruption of pregnancy when possible, depending on the term, and when accepted by the patient.