Plasmocytose sanguine et dengue : une anomalie biologique sous-estimée ?

Introduction

A significant peripheral blood plasmacytosis is a rare finding associated with viral infections. We reported five consecutive cases of dengue virus infection, with circulating plasma cells.

Case reports

Three women and two men, aged 26 to 75 years, had returned from French West Indies less than one week before the onset of the symptoms (mean: 2.5 days). The transient blood plasmacytosis was variable in intensity (0.1 to 0.8 G/L) with a maximal level between the fourth and the seventh day following the onset of the symptoms, and was associated in four patients, with activated lymphocytes and lympho-plasma cells.

Conclusion

Reactive plasmacytosis during dengue fever is common and probably underestimated because it is transient and only identified by careful microscopic examination of a blood smear. Plasmacytosis could be explained by the intensity of the immunological response and the production of large amount of interleukins.     

Pretransplant Sensitization Against Angiotensin II Type 1 Receptor Is a Risk Factor for Acute Rejection and Graft Loss

The angiotensin II type 1 receptor (AT₁R) is an emerging target of functional non‐HLA antibodies (Ab). We examined the potential of determining the degree of presensitization against AT₁R as a risk factor for graft survival and acute rejection (AR). The study included 599 kidney recipients between 1998 and 2007. Serum samples were analyzed in a blinded fashion for anti‐AT₁R antibodies (AT₁R‐Abs) using a quantitative solid‐phase assay. A threshold of AT₁R‐Ab levels was statistically determined at 10 U based on the time to graft failure. An extended Cox model determined risk factors for occurrence of graft failure and a first AR episode. AT₁R‐Abs >10 U were detected in 283 patients (47.2%) before transplantation. Patients who had a level of AT₁R‐Abs >10 U had a 2.6‐fold higher risk of graft failure from 3 years posttransplantation onwards (p = 0.0005) and a 1.9‐fold higher risk of experiencing an AR episode within the first 4 months of transplantation (p = 0.0393). Antibody‐mediated rejection (AMR) accounted for 1/3 of AR, whereby 71.4% of them were associated with >10 U of pretransplant AT₁R‐Abs. Pretransplant anti‐AT₁R‐Abs are an independent risk factor for long‐term graft loss in association with a higher risk of early AR episodes.     

Task-Specific Perturbation Training Improves the Recovery Stepping Responses by Women With Knee Osteoarthritis Following Laboratory-Induced Trips

Trip-specific training improves the kinematics of trip-specific compensatory stepping response (CSR) in the laboratory and reduces prospectively measured trip-related fall-rate of middle age and older women. We examined whether one session of trip-specific perturbation training could improve recovery step kinematics in women with knee osteoarthritis (OA), a condition known to increase fall risk. Seventeen women with self-reported symptomatic knee OA (age 61.1 ± 7.7 years, body mass index [BMI] 29.7 ± 5.9 kg/m²) and 22 control women (age 59.5 ± 6.8 years, BMI 28.4 ± 6.2 kg/m²) completed a brief training protocol consisting of 20 trials of treadmill-delivered trip-specific perturbations. We assessed pre- and post-training recovery step length and trunk kinematics at the instant of recovery step completion. Repeated-measures analysis of variance was used to determine the significance of between-group differences following the training protocol, and to evaluate the significance of within-group pre-to-post changes in the variables of interest. The group by training interaction effects for step length (p = 0.466), trunk flexion angle (p = 0.751), and trunk angular velocity (p = 0.413) were not significant and the pre-to-post changes in step length were not significant (p = 0.286). However, pre-to-post trunk flexion angle improved by 26% and 34% in the OA and control groups, respectively (p < 0.001) and trunk flexion angular velocity decreased by 193% in the OA group and by 32% in the control group, respectively (p < 0.001), often reflecting a transition to the direction of extension. The results suggest that trip-specific training can improve CSR kinematics in women with knee OA. It is important to determine, the effectiveness of trip-specific training in decreasing trip-specific fall-rate by women with knee OA. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:663–669, 2020     

Cytokine activation during attacks of the hyperimmunoglobulinemia D and periodic fever syndrome

The hyperimmunoglobulinemia D and periodic fever (hyper-IgD) syndrome is typified by recurrent febrile attacks with abdominal distress, joint involvement (arthralgias/arthritis), headache, skin lesions, and an elevated serum IgD level (> 100 U/mL). This familial disorder has been diagnosed in 59 patients, mainly from Europe. The pathogenesis of this febrile disorder is unknown, but attacks are joined by an acute-phase response. Because this response is considered to be mediated by cytokines, we measured the acute-phase proteins C-reactive protein (CRP) and soluble type-II phospholipase A2 (PLA2) together with circulating concentrations and ex vivo production of the proinflammatory cytokines interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-6, and tumor necrosis factor alpha (TNF alpha) and the inhibitory compounds IL-1 receptor antagonist (IL-1ra), IL-10, and the soluble TNF receptors p55 (sTNFr p55) and p75 (sTNFr p75) in 22 patients with the hyper-IgD syndrome during attacks and remission. Serum CRP and PLA2 concentrations were elevated during attacks (mean, 213 mg/L and 1,452 ng/mL, respectively) and decreased between attacks. Plasma concentrations of IL-1 alpha, IL-1 beta, or IL-10 were not increased during attacks. TNF alpha concentrations were slightly, but significantly, higher with attacks (104 v 117 pg/mL). Circulating IL-6 values increased with attacks (19.7 v 147.9 pg/mL) and correlated with CRP and PLA2 values during the febrile attacks. The values of the antiinflammatory compounds IL-1ra, sTNFr p55, and sTNFr p75 were significantly higher with attacks than between attacks, and there was a significant positive correlation between each. The ex-vivo production of TNF alpha, IL-1 beta, and IL-1ra was significantly higher with attacks, suggesting that the monocytes/macrophages were already primed in vivo to produce increased amounts of these cytokines. These findings point to an activation of the cytokine network, and this suggests that these inflammatory mediators may contribute to the symptoms of the hyper-IgD syndrome.     

T cells from patients with Hodgkin's disease have a defective T-cell receptor zeta chain expression that is reversible by T-cell stimulation with CD3 and CD28

To investigate the mechanisms underlying the deficiency of T lymphocytes from patients with Hodgkin's disease, we investigated the expression of the T-cell receptor (TCR) zeta chain in patients with Hodgkin's disease. By flow cytometry using an anti-zeta chain monoclonal antibody, peripheral blood T lymphocytes from patients with untreated Hodgkin's disease were shown to express decreased levels of the TCR zeta chain. After stimulation by combined CD3 and CD28 cross- linking, T cells from Hodgkin's disease patients upregulated zeta chain protein expression to normal values within 48 hours and achieved a cytolytic potential and levels of interleukin (IL)-2 secretion that were not different from T cells obtained from healthy controls. These results show that downregulation of the TCR zeta chain in Hodgkin's T lymphocytes is a reversible event. Costimulation of CD3 and CD28 is a novel approach for overcoming the T-cell deficiency in Hodgkin's disease and might be exploited clinically. As upregulation of the zeta chain can also be achieved using bispecific monoclonal antibodies (BI- MoAbs) with specificity for tumor antigens and CD3 and CD28, respectively, an immunotherapy with CD3/CD30 and CD28/CD30 Bi-MoAbs may overcome and should therefore, not be jeopardized by the inherent T- cell deficiency in patients with Hodgkin's disease.     

High incidence of monoclonal proteins in the serum and urine of chronic lymphocytic leukemia patients

Chronic lymphocytic leukemia (CLL) is generally considered a nonsecretory B cell immunoproliferative disorder. Conventional electrophoretic and immunoelectrophoretic methods have revealed serum monoclonal proteins in less than 10% of these patients. However, there is increasing experimental evidence from in vitro studies demonstrating that CLL cells may secrete immunoglobulins, particularly free light chains. We examined the serum and urine of 36 consecutive CLL patients for monoclonal proteins using sensitive immunochemical methods (high resolution agarose gel electrophoresis combined with immunofixation). The results obtained were correlated with the Rai stage, quantitative immunoglobulin levels, and lymphocyte membrane immunoglobulin phenotype of the leukemic cells. Twenty-three monoclonal proteins were identified in the serum or urine of 22 patients, an incidence of 61%. Six patients had serum monoclonal proteins, seven had only urinary monoclonal proteins, and nine had monoclonal proteins in serum and urine. In every instance the monoclonal protein was the same light chain type as expressed on the leukemic cells. Our findings suggest that the monoclonal proteins observed in the serum or urine of CLL patients are secretory products of the tumor cells and that their discovery is a function of the sensitivity of the method used for their detection.     

Immune responses to major histocompatibility complex homozygous lymphoid cells in murine F1 hybrid recipients: implications for transfusion-associated graft-versus-host disease

Graft-versus-host disease (GVHD) is currently encountered after bone marrow transplantation and transfusion. GVHD associated with transfusion (TA-GVHD) in apparently immunocompetent recipients has been recently reported with increasing frequency. A consistent finding in many of these cases is that the recipient received blood from a donor homozygous for one of the recipient's HLA haplotypes. However, the observed frequency of TA-GVHD is much lower than the estimated probability of this donor/recipient combination. The potential role of recipient immune responses in controlling TA-GVHD was investigated using an analogous murine model in which GVHD is induced by the injection of parental lymphoid cells into unirradiated F1 hybrid recipients. The effect of various immune manipulations of the recipient of GVHD induction was assessed by determining the number of donor lymphoid cells required to induce GVHD responses. Whereas depletion of recipient CD4+ cells increased the number of donor cells needed to induce GVHD, depletion of recipient CD8+ and natural killer cells resulted in fewer donor cells being needed to induce a GVHD response. These studies suggest a central role for functioning recipient CD8 and natural killer cells in the down-regulation of TA-GVHD development in recipients.