Search

A letter to the editor on T-cell activation antigen CD26 in Type 1 Diabetes Mellitus is presented.

Type 1 diabetes is an autoimmune process predominantly T-cell mediated. CD26 plays a role in T-cell costimulation, migration, memory development, thymic maturation and emigration patterns. In peripheral blood from 55 patients with type 1 diabetes and 20 healthy controls, CD4(+) and CD8(+) T cells expressing CD26 were differentiated into naïve (N, CD45RA(+)CCR7(+)), central memory (CM, CD45RA(-)CCR7(+)), effector memory (EM, CD45RA(-)CCR7(-)), and terminally differentiated effector memory (TEMRA, CD45RA(+)CCR7(-)). In type 1 diabetes, CD4(+) and CD8(+) T cells expressing CD26 showed a distinctive differentiation profile: percentages and absolute numbers of CM and N cells were reduced, whereas those of TEMRA cells were markedly increased. The indices of intermediate- and long-term glycaemic control were associated negatively with the number of CM and N cells while positively with the number of TEMRA cells. The considerable accumulation of TEMRA T cells in our patients suggests life-long stimulation by protracted antigen exposure (viruses, other agents or residual self-antigens?) or a homeostatic defect in the regulation/contraction of immune responses.

Proper cellular function requires the maintenance of mitochondrial membrane potential (MMP) sustained by the electron transport chain. Mitochondrial dysfunction is believed to play a role in the development of diabetes and diabetic complications possibly because of the active generation of free radicals. Since MMP can be investigated in clinical settings using fluorescent probes and living whole blood cells, mitochondrial membrane alterations have been observed in some chronic disorders. We have used the mitochondrial indicator 5,5',6,6'-tetra chloro-1,1',3,3'-tetraethylbenzimidazolyl-carbocyanine iodide (JC-1) in conjunction with flow cytometry to measure the MMP in peripheral blood granulocytes from type 1 diabetes (T1D) families. The intracellular ROS levels and the respiratory burst activity were also measured. Leukocyte MMP was elevated in 20 T1D patients and their 20 non-diabetic siblings compared with 25 healthy subjects without family history of T1D. Fasting plasma glucose was the only correlate of MMP. If confirmed by further observations, the functional implications of mitochondrial hyperpolarisation (probably different among different cells) will require extensive investigation.

Background: It is common experience that retreating patients too early after a course of intensive chemotherapy predisposes to opportunistic infections despite apparently normal lymphocyte levels., Objectives: The extent of replication of persistent viruses that cause no obvious disease (and hence need no treatment) might better define when a patient has recovered from functional immune deficiency., Study Design: We used real-time polymerase chain reaction to monitor the kinetics of plasma torquetenovirus (TTV) viremia in hematological patients undergoing autologous hematopoietic stem cell transplantation as support to high-dose chemotherapy (HSCT)., Results: Independently from underlying hematological disease and therapeutic regimen, TTV viremia increased post-HSCT, and this increase paralleled the increase of circulating CD8(+)CD57(+) T lymphocytes, known to represent an indirect marker of functional immune deficiency. Subsequently, within a matter of months, TTV levels returned to baseline values, at a pace that appeared to be constant over time., Conclusion: Monitoring of TTV viremia represents a unique opportunity to follow functional immune reconstitution in immunosuppressed patients. Also, the size of the TTV viremia increases resulting from immunosuppressive treatments might be of guidance in determining the appropriate time interval before delivery of a next course of therapy.

Aims: Morphology on bone marrow biopsy (BMB) samples has historically been the primary method used to detect bone marrow (BM) infiltration in B-cell non-Hodgkin's lymphoma (NHL), while fl ow cytometry (FC) and PCR assays have been generally used as ancillary methods. In this study we evaluated a combined approach utilizing all three methods to detect BM infiltration in patients with NHL both at diagnosis and after therapy., Materials and Methods: We analyzed 193 patients with NHL, who received simultaneous BMB, FC and PCR assays. Morphology on histologic specimens was used to assess infiltration pattern and immunohistochemistry, FC to analyze immunophenotype, PCR to identify IgH rearrangement, BCL-1/JH and BCL-2/JH translocation., Results: Morphology, FC and PCR assays agreed in 142 cases (73.5%) with more concordance at initial diagnosis than during postchemotherapy follow-up. PCR was the single best-performing test, while combination of morphology and PCR yielded a higher sensitivity than individual methods and was similar to PCR + FC. We observed little added benefit using a third approach., Conclusion: Given the initial importance of histological information evident by morphology, our data suggest that combination of morphology and PCR should be considered the gold standard for evaluation of BM infiltration at diagnosis, while combination of PCR + FC should be employed during post-treatment follow-up.

Aim: Several neutrophil functions can be modified by rhG-CSF administration. Neutrophil morphology changes in the course of treatment with Filgrastim (nonglycosylated rhG-CSF), along with impairment of chemotaxis. Both morphology and chemotaxis are not affected by treatment with Lenograstim (glycosylated rhG-CSF). Thus, we evaluated actin polymerization in neutrophils induced by treatment with the two forms of rhG-CSF. In fact, actin polymerization is crucial for neutrophil motility., Materials and Methods: We evaluated twelve healthy subjects undergoing peripheral blood stem cells (PBSC) mobilization for allogeneic transplantation to HLA-identical siblings. Neutrophils were isolated by peripheral venous blood before and after administration of either Filgrastim (six PBSC donors) or Lenograstim (six PBSC donors). Actin polymerization was investigated by a flow cytometric assay, using FITC-phalloidin as a specific probe for F-actin, and two parameters were measured: spontaneous actin polymerization in resting neutrophils; fMLP-stimulated actin polymerization. Results were expressed as relative F-actin content. Fifteen blood donors were studied as a control group., Results: Filgrastim administration induced an increased relative F-actin content in resting neutrophils; however, no further actin polymerization was observed after fMLP stimulation. Neutrophils from subjects treated with Lenograstim showed a normal behaviour in terms of both spontaneous and stimulated actin polymerization., Conclusions: Glycosylated and nonglycosylated rhG-CSF differently affect actin polymerization in newly generated neutrophils. Such effects may explain some previous findings concerning both morphology and chemotactic properties and may be due to different effects of the two forms of rhG-CSF on proteins involved in neutrophil motility regulation.

A cytofluorimetric method to detect antineutrophil antibodies was carried out in sixty adults suffering from chronic idiopathic neutropenia (5 patients with severe neutropenia, 16 with moderate neutropenia, 39 with mild neutropenia). Both the direct and the indirect tests were carried out using F(ab')2 goat anti-human FITC-conjugates immunoglobulins on whole blood samples. Fifteen patients (25%) were found to have antineutrophil antibodies both on the neutrophil surface and in serum. Most positive patients were suffering from severe neutropenia (4 patients) and moderate neutropenia (8 patients). Only four positive patients were suffering from infections.