Reduced levels of T-cell subsets CD4+ and CD8+ in homozygous sickle cell anaemia patients with splenic defects

T-lymphocyte subsets were studied in two patient groups: (1) 50 patients with homozygous sickle cell anaemia (SCA) (mean age 12 (range 3-32) years old) in good health at the time of the study who showed no infectious complication. (2) 50 patients (mean age 13 (range 4-29) years old) with normal haemoglobin rate. The global response revealed a significant increase in levels of CD3+ (P=0.04) and CD8+ (P=0.04) cells when compared with the control group, there was no significant difference in levels of CD4+ cells (P=0.05) between the two groups. However, there was a relationship between T-cell subpopulation levels and spleen status. The average values of T-cell subsets (CD4+ and CD8+) in patients with SCA-induced splenic defects (asplenic, splenomegaly or splenectomized patients) were significantly reduced when compared to SCA patients with normal spleens and the control groups. These data show that T-cell activity was reduced in patients with splenic defects. A correlation between splenic status and a perturbed host defence system in patients with SCA suggests that monitoring T-cell subsets might have prognostic value in the course of sickle cell disease.     

Cellular human immunodeficiency virus (HIV)-protective factors: a comparison of HIV-exposed seronegative female sex workers and female blood donors in Abidjan,Côte d'Ivoire

Cellular factors that may protect against human immunodeficiency virus (HIV) infection were investigated in 27 HIV-exposed seronegative (ESN) female sex workers (FSWs) and 27 HIV-seronegative female blood donors. Compared with blood donors, ESN FSWs had significantly decreased expression levels of C-X-C chemokine receptor 4 (CXCR4), but not of C-C chemokine receptor 5, on both memory (P<.001) and naive (P=.041) CD4(+) T cells. CXCR4 down-regulation was associated with prolonged duration of commercial sex work by ESN FSWs. CD38 expression on CD8(+) T cells was significantly increased among ESN FSWs, compared with that among blood donors (P=.017). There were no differences in HLA-DR and CD62L expression between blood donors and ESN FSWs. Proportions of T cells producing the beta-chemokines RANTES (regulated on activation, normally T cell-expressed and -secreted), macrophage inflammatory protein (MIP)-1alpha, and MIP-1beta or the cytokines interleukin (IL)-2, IL-4, interferon-gamma, and tumor necrosis factor-alpha, were similar in the 2 groups. These data indicate that ESN FSWs differ from HIV-seronegative female blood donors with respect to immunological factors that have no clear protective potential against HIV transmission.     

Positive association between beta-chemokine-producing T cells and HIV type 1 viral load in HIV-infected subjects in Abidjan, Côte d'Ivoire

The role of beta-chemokines in controlling HIV replication in vivo is still controversial. Therefore, the association between HIV-1 plasma viral load and the capacity of CD4(+) and CD8(+) T cells to produce beta-chemokines was studied in 28 antiretroviral drug-na?ve HIV-1-infected female sex workers in Abidjan, C?te d'Ivoire. Percentages of beta-chemokine-positive T cells were measured in peripheral blood mononuclear cells by flow cytometry after intracellular staining for RANTES (regulated on activation, normal T expressed and secreted), macrophage inflammatory protein (MIP)-1alpha, and MIP-1beta. HIV-1-infected subjects had higher percentages of MIP-1alpha- and MIP-1beta-positive CD4(+) and CD8(+) T cells (p < 0.02) and of RANTES-positive CD8(+) T cells (p = 0.054) than uninfected controls. Percentages of RANTES- and MIP-1beta-positive CD8(+) T cells correlated directly with HIV-1 plasma viral load (p < 0.02). Percentages of beta-chemokine-positive CD4(+) and CD8(+) T cells correlated directly with percentages of HLA-DR-positive T cells (p < 0.02) and inversely (except RANTES in CD4(+) T cells) with absolute numbers of CD4(+) T cells (p < 0.05) in peripheral blood. These data indicate that increased percentages of beta-chemokine-producing T cells in HIV-1-infected subjects correlate with disease progression and are a sign of viremia-driven chronic T cell activation.     

Anti-GBM nephritis in the mouse: severe proteinuria in the heterologous phase

Summary Highly reproducible anti glomerular basement membrane (GBM) nephritis has been induced in the mouse after a single injection of rabbit or goat antibody against purified homologous GBM. The severity of albuminuria was closely related to the amount of antibody given. With doses of 4 mg or more, low serum albumin concentrations, sometimes accompanied by ascites and oedema, were observed after 1 week. Glomerular injury was characterized by an initial accumulation of polymorphonuclear granulocytes followed by thrombosis and necrosis, the extent of which defined the outcome of the glomerulonephritis. With high doses of antibody the exudative lesions entered a chronic phase, while at doses lower than 2 mg remission of the lesions occurred. Immunofluorescence studies showed prompt linear fixation of the injected anti-bodies to the glomerular capillary wall, accompanied by immediate binding of C3 in a fine granular pattern. Fibrin deposits appeared at 2 h in some glomeruli, increased thereafter, and were present after one day in more than 90% of the glomeruli in mice that had received 4 mg of antibody. This new reproducible model in the mouse is suited for the study of the relationship between activation of mediator systems, histological lesions, and proteinuria.     

Measurement of HIV-1 CRF02_AG-specific T cell responses indicates the dominance of a p24gag epitope in blood donors in Abidjan, Cote d'Ivoire

Characterization of human immunodeficiency virus (HIV)-1-specific immune responses against subtypes circulating in areas where the virus is endemic is critical for the design of candidate vaccines. In Cote d'Ivoire, the most prevalent HIV-1 subtype is CRF02_AG. We detected T cell responses to CRF02_AG consensus p24(gag) or protease peptides in 81% of HIV-1- or HIV-1/2-infected blood donors in Abidjan, Cote d'Ivoire. Both the magnitude and the breadth of interferon- gamma enzyme-linked immunospot responses were inversely correlated with plasma viral load. One frequently recognized peptide in p24(gag) was mapped to the optimal epitope (TPQDLNMML). Further studies of this epitope may be important for the development of HIV-1 vaccines for West Africa and West-Central Africa.     

Serological status: a predictor of response to intensive therapy in rheumatoid arthritis

BackgroundRheumatoid arthritis is the most common chronic inflammatory disease in the UK. Serological status such as rheumatoid factor (RF) and anti-citrullinated peptide antibody (ACPA) positivity predict poor outcomes. Early intensive treatment regimens targeting remission reduce disease activity, structural damage, and long-term disability. However, we do not know whether all patients with active disease should have such intensive treatment regimens. Can serological status be used to predict the need for intensive therapy?MethodsWe analysed samples from a published randomised controlled trial which compared four treatment regimens in patients with early active rheumatoid arthritis (disease duration <2 years): methotrexate monotherapy, double therapy (methotrexate plus either ciclosporin or prednisolone), and triple therapy (methotrexate plus ciclosporin plus prednisolone). The trial randomised 467 patients (68% female, median age 54 years [IQR 46–63]). Disease activity was assessed with the disease activity score of 28 joints (DAS28). Remission was defined as DAS28 less than 2·6 at 24 months. RF isotypes (IgM and IgA) and ACPA levels were measured with commercial ELISA kits. Statistical analysis used Pearson's chi-squared test.Findings402 (86%) patients were positive for IgM RF, 346 (74%) for IgA RF, and 346 (74%) for ACPA. 98 (21%) patients achieved remission at 24 months. In RF IgM negative cases (n=65) the proportion of patients achieving remission at 24 months was similar in all treatment groups (25%, 22%, and 30% for monotherapy, double therapy, and triple therapy, respectively). In RF IgM positive cases, significantly fewer patients achieved remission with monotherapy (13/65, 17%) and double therapy (24/157, 15%) than with triple therapy (27/80, 34%) (p=0·001). There were similar, consistent findings with IgA RF and ACPA, with significantly more seropositive patients achieving remission with triple therapy than with monotherapy.InterpretationContemporary treatment of rheumatoid arthritis emphasises the use of intensive therapy to achieve remission. However, we have shown that not all patients require such an aggressive approach to therapy. Given the heterogeneity of the diease, treatment should be personalised to the individual, which would minimise costs of treatment as well as potentially toxic side-effects. Our study shows that only seropositive patients with rheumatoid arthritis should be given more intensive therapies.FundingNational Institute for Health Research.     

Bone marrow transplantation for patients with Philadelphia chromosome- positive acute lymphoblastic leukemia

We report the treatment outcome of allogeneic bone marrow transplantation in ten patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Six patients are alive and well for 6 to 30 months (median 19 months) after transplantation. Four patients died with transplant related complications. In view of the poor prognosis associated with this disease, marrow ablation followed by allogeneic or syngeneic marrow grafting may be the preferred treatment modality if a suitable marrow donor is available.     

Comparison of clinical and self-reported diagnoses for participants on a community-based arthritis self-management programme

OBJECTIVE: With the advent of community-based arthritis education programmes, it is important to determine the accuracy of participants' self-reported diagnoses. The purpose of this study was to determine the level of agreement between general practitioner (GP)-recorded and self- reported diagnoses of participants attending an Arthritis Self- Management Programme (ASMP). METHODS: Participants enrolling on the ASMP were asked to (a) identify their type of arthritis via a self- administered postal questionnaire and (b) obtain a written confirmation of their diagnosis from their GP. The sample (n = 613) comprised mainly women (83%) with a mean age of 58.8 yr (S.D. 12.6) and a mean disease duration of 15.4 yr (S.D. 12.5). RESULTS: Participants' self-reported diagnoses were confirmed by GPs in 534 cases [87.1%, 95% confidence interval (CI): 84.4 89.8%]. Confirmed diagnoses were reported by 86.9% (95% CI: 83.1-90.7%) of those with osteoarthritis (OA) and 96.1% (95% CI: 93.6 98.6%) of those with rheumatoid arthritis (RA). The concordance rate for all other types of arthritis combined was lower at 60.5% (95% CI: 49.5-71.5%). There were no significant differences with respect to age, gender, education, physical functioning, duration of disease and number of GP visits between those who correctly identified their type of arthritis and those who did not. CONCLUSIONS: This study suggests that the majority of RA and OA participants attending an arthritis education programme can correctly identify their specific type of arthritis.