ObjectivePsoriatic arthritis (PsA) is associated with HLA class I genes, in contrast to the association with HLA class II in rheumatoid arthritis (RA). Since IL-17+ cells are considered important mediators of synovial inflammation, we sought to determine whether IL-17–producing CD8+ T cells may be found in the joints of patients with PsA and whether these cells might contribute to the disease process.MethodsMononuclear cells from paired samples of synovial fluid (SF) and peripheral blood (PB) from patients with PsA or patients with RA were stimulated ex vivo, and CD4− T cells were examined by flow cytometry for cytokine expression, cytotoxic markers, and frequencies of γ/δ or mucosal-associated invariant T cells. Clinical measures of arthritis activity (C-reactive protein [CRP] level, erythrocyte sedimentation rate [ESR], Disease Activity Score in 28 joints [DAS28]) and power Doppler ultrasound (PDUS) scores for the presence of active synovitis in the aspirated knee were recorded and assessed for correlations with immunologic markers.ResultsWithin the CD3+ T cell compartment, both IL-17+CD4− (predominantly CD8+) and IL-17+CD4+ T cells were significantly enhanced in the SF compared to the PB of patients with PsA (P = 0.0003 and P = 0.002, respectively; n = 21), whereas in patients with RA, only IL-17+CD4+ T cells were increased in the SF compared to the PB (P = 0.008; n = 14). The frequency of IL-17+CD4− T cells in PsA SF was positively correlated with the CRP level (r = 0.52, P = 0.01), ESR (r = 0.59, P = 0.004), and DAS28 (r = 0.52, P = 0.01), and was increased in patients with erosive disease (P < 0.05). In addition, the frequency of IL-17+CD4− T cells positively correlated with the PDUS score, a marker for active synovitis (r = 0.49, P = 0.04).ConclusionThese results show, for the first time, that the PsA joint, but not the RA joint, is enriched for IL-17+CD8+ T cells. Moreover, the findings reveal that the levels of this T cell subset are correlated with disease activity measures and the radiographic erosion status after 2 years, suggesting a previously unrecognized contribution of these cells to the pathogenesis of PsA.

Two hundred and eighty-eight newly diagnosed cases of leukemia (164 males and 124 females, 167 adults and 121 children, 245 acute and 43 chronic, 151 myeloid and 137 lymphoid), aged between 6 weeks and 78 years, were examined for eye changes in the oncology wards within 2 days of diagnosis before starting chemotherapy. Ocular lesions were present in 102 patients (35.4%) – retinal vascular changes in 91 (31.6%); infiltration of ocular tissues in 5 (1.7%), and neuro-ophthalmic signs in 6 (2.1%) cases. Some of the patients had more than one ocular lesion in one or both eyes. The eye changes were seen more often in adults (49.1%) than in children (16.5%), and in myeloid leukemia (41.0%) than in lymphoid leukemia (29.2%). Eye symptoms were present in 29 patients (10%) at initial diagnosis. Since ocular lesions were detected in many asymptomatic leukemia patients, eye examination should be included as a part of routine evaluation at initial diagnosis in these patients.

Treg cells are critical for the prevention of autoimmune diseases and are thus prime candidates for cell-based clinical therapy. However, human Treg cells are “plastic”, and are able to produce IL-17 under inflammatory conditions. Here, we identify and characterize the human Treg subpopulation that can be induced to produce IL-17 and identify its mechanisms. We confirm that a subpopulation of human Treg cells produces IL-17 in vitro when activated in the presence of IL-1β, but not IL-6. “IL-17 potential” is restricted to population III (CD4+CD25hiCD127loCD45RA−) Treg cells expressing the natural killer cell marker CD161. We show that these cells are functionally as suppressive and have similar phenotypic/molecular characteristics to other subpopulations of Treg cells and retain their suppressive function following IL-17 induction. Importantly, we find that IL-17 production is STAT3 dependent, with Treg cells from patients with STAT3 mutations unable to make IL-17. Finally, we show that CD161+ population III Treg cells accumulate in inflamed joints of patients with inflammatory arthritis and are the predominant IL-17-producing Treg-cell population at these sites. As IL-17 production from this Treg-cell subpopulation is not accompanied by a loss of regulatory function, in the context of cell therapy, exclusion of these cells from the cell product may not be necessary.

ABSTRACT.Purpose: To determine the prevalence of ocular manifestations in childhood acute leukaemia at the time of presentation. Methods: Eighty-two children with acute leukaemia were examined for ocular lesions within two days of diagnosis before starting chemotherapy. The detailed ocular examination of both eyes was carried out by the ophthalmologist irrespective of the presence or absence of eye symptoms in all cases. Results: Only 3 out of 82 children presented with eye symptoms (3.6%). However, ocular changes were found in 14 children (17%); ten with lymphoblastic and four with myeloid leukaemia. The ocular lesions observed were proptosis, intraretinal haemorrhages, white centered haemorrhages, cotton wool spots, macular haemorrhage, subhyaloid haemorrhage, vitreous haemorrhage, papilloedema, cortical blindness, sixth nerve palsy, and exudative retinal detachment with choroidal infiltration. Conclusion: In view of the high prevalence of asymptomatic ocular lesions in childhood acute leukaemia, routine ophthalmic examination should be included as a part of evaluation at the time of diagnosis.

ObjectiveConflicting evidence exists regarding the suppressive capacity of Treg cells in the peripheral blood (PB) of patients with rheumatoid arthritis (RA). The aim of this study was to determine whether Treg cells are intrinsically defective in RA.MethodsUsing a range of assays on PB samples from patients with chronic RA and healthy controls, CD3+CD4+CD25+CD127low Treg cells from the CD45RO+ or CD45RA+ T cell compartments were analyzed for phenotype, cytokine expression (ex vivo and after in vitro stimulation), suppression of Teff cell proliferation and cytokine production, suppression of monocyte‐derived cytokine/chemokine production, and gene expression profiles.ResultsNo differences between RA patients and healthy controls were observed with regard to the frequency of Treg cells, ex vivo phenotype (CD4, CD25, CD127, CD39, or CD161), or proinflammatory cytokine profile (interleukin‐17 [IL‐17], interferon‐γ [IFNγ], or tumor necrosis factor [TNF]). FoxP3 expression was slightly increased in Treg cells from RA patients. The ability of Treg cells to suppress the proliferation of T cells or the production of cytokines (IFNγ or TNF) upon coculture with autologous CD45RO+ Teff cells and monocytes was not significantly different between RA patients and healthy controls. In PB samples from some RA patients, CD45RO+ Treg cells showed an impaired ability to suppress the production of certain cytokines/chemokines (IL‐1β, IL‐1 receptor antagonist, IL‐7, CCL3, or CCL4) by autologous lipopolysaccharide‐activated monocytes. However, this was not observed in all patients, and other cytokines/chemokines (TNF, IL‐6, IL‐8, IL‐12, IL‐15, or CCL5) were generally suppressed. Finally, gene expression profiling of CD45RA+ or CD45RO+ Treg cells from the PB revealed no statistically significant differences between RA patients and healthy controls.ConclusionOur findings indicate that there is no global defect in either CD45RO+ or CD45RA+ Treg cells in the PB of patients with chronic RA.

No abstract

In this prospective study, we examined stool specimens from children with cancer receiving chemotherapy who were admitted for fever to the Universiti Sains Malaysia Hospital in Kota Baru, Kelantan. Stool specimens were examined for ova and cysts of parasites. Over a period of 15 months, there were 129 febrile episodes in 50 children with cancer and, in all, 237 stool specimens were examined. Sixty-six per cent of febrile episodes were associated with neutropenia and 9 per cent were associated with diarrhoea. Stool parasites were found in 42 per cent of children. The most common were helminths, followed by protozoa. Trichuris trichiura was the most common parasite (24 per cent), followed by Ascaris lumbricoides (22 per cent). Hookworm was found in 2 per cent. Giardia lamblia was found in 6 per cent of children, Blastocystis hominis in 4 per cent, and Cryptosporidium parvum in 2 per cent.

No abstract