Derangement of the T‐cell repertoire in patients with B‐cell non‐Hodgkin's lymphoma

Although a number of studies suggest that different immune pathways may play a role in the pathogenesis of non‐Hodgkin's lymphomas (NHL), the shape of the T‐cell compartment has been only superficially explored in these patients. In our study, we analyzed the peripheral T‐cell receptor (TCR) repertoire and the distribution of different T‐cell subsets – including regulatory T cells (Treg) – in 30 patients with NHL, by combining flow cytometry and spectratyping. We first demonstrated by flow cytometry an increased frequency of expanded T‐cell subpopulations expressing the same TCR beta variable (BV) subfamilies in CD8+ cells from NHL patients when compared with healthy controls, beside a higher frequency of Treg. Moreover, NHL patients were characterized by a higher percentage of BVs showing a skewed CDR3 profile both in CD4+ and CD8+ cells when analyzed by spectratyping. Our data suggest that the T‐cell branch of the immune system of patients with B‐cell NHL is deeply deranged, as witnessed by the increased degree of activation and skewing of their TCR repertoire along with the higher frequency of Treg.     

Use of positron emission tomography with methyl‐11C‐choline and 2‐18F‐fluoro‐2‐deoxy‐D‐glucose in comparison with magnetic resonance imaging for the assessment of inflammatory proliferation of synovium

Objective

To compare positron emission tomography (PET) and magnetic resonance imaging (MRI) in the evaluation of inflammatory proliferation of synovium.

Methods

Ten patients (mean ± SD age 36 ± 13 years) with inflammatory joint disease and with clinical signs of inflammation of the joint were studied. A new tracer for cellular proliferation, methyl‐¹¹C‐choline (¹¹C‐choline), and a widely used tracer for the detection of inflammation and cancer, 2‐¹⁸F‐fluoro‐2‐deoxy‐D ‐glucose (¹⁸F‐FDG), were applied for PET imaging, and the results were compared with the findings from gadolinium diethylenetriaminepentaacetic acid–enhanced MR images. The uptake of ¹¹C‐choline and ¹⁸F‐FDG in the inflamed synovium was measured and expressed as the standardized uptake value (SUV) and the kinetic influx constant (K_i) obtained from graphic analysis, and these values were compared with quantitative values on MRI. Synovial volumes were measured on the coronal contrast‐enhanced T1‐weighted MR images using the standard software of the MR imager.

Results

All patients showed high accumulation of both ¹¹C‐choline and ¹⁸F‐FDG at the site of arthritic changes, where quantification of the tracer uptake was performed. The SUV of ¹¹C‐choline was 1.5 ± 0.9 gm/ml (mean ± SD; n = 10) and the SUV of ¹⁸F‐FDG was 1.9 ± 0.9 gm/ml (n = 10) (P = 0.017). The K_i of ¹¹C‐choline (mean ± SD 0.048 ± 0.042 minute⁻¹) was 8‐fold higher than the K_i of ¹⁸F‐FDG (0.006 ± 0.003 minute⁻¹) (P = 0.009). Both the uptake of ¹¹C‐choline and the uptake of ¹⁸F‐FDG correlated highly with the volume of synovium; the highest correlation was observed with the K_i of ¹¹C‐choline (r = 0.954, P < 0.0001).

Conclusion

In the use of PET scans,¹¹C‐choline can be regarded as a promising tracer for quantitative imaging of proliferative arthritis changes. Nevertheless, subsequent prospective studies with larger numbers of patients are necessary to further characterize the relationship between the findings on PET imaging and the clinical and functional measures of inflammation.

     

Inhibition of adjuvant‐induced arthritis by DNA vaccination with the 70‐kd or the 90‐kd human heat‐shock protein: Immune cross‐regulation with the 60‐kd heat‐shock protein

Objective

Adjuvant arthritis can be induced in Lewis rats by immunization with Mycobacterium tuberculosis (Mt). The mycobacterial 65‐kd heat‐shock protein (Hsp65) is targeted by arthritogenic T cells. However, Hsp65 and the mycobacterial 71‐kd heat‐shock protein are also recognized by T cells that can down‐regulate adjuvant‐induced arthritis (AIA). We have recently demonstrated that vaccination with human Hsp60 DNA inhibits AIA. The present study was undertaken to analyze the role of the T cell responses to self HSP molecules other than Hsp60 in the control of AIA.

Methods

Lewis rats were immunized with DNA vaccines coding for human Hsp70 or Hsp90 (Hsp70 plasmid [pHsp70] or pHsp90), and AIA was induced. The T cell response to Mt, Hsp60, Hsp70, and Hsp90 (proliferation and cytokine release) was studied, and the T cell response to Hsp60 was mapped with overlapping peptides.

Results

The Hsp70 or Hsp90 DNA vaccines shifted the arthritogenic T cell response from a Th1 to a Th2/3 phenotype and inhibited AIA. We detected immune crosstalk between Hsp70/90 and Hsp60: both the Hsp70 and Hsp90 DNA vaccines induced Hsp60‐specific T cell responses. Similarly, DNA vaccination with Hsp60 induced Hsp70‐specific T cell immunity. Epitope mapping studies revealed that Hsp60‐specific T cells induced by pHsp70 vaccination reacted with known regulatory Hsp60 epitopes.

Conclusion

T cell immunity to Hsp70 and to Hsp90, like Hsp60‐specific immunity, can modulate the arthritogenic response in AIA. In addition, our results suggest that the regulatory mechanisms induced by Hsp60, Hsp70, and Hsp90 are reinforced by an immune network that connects their reactivities.

     

Assessment of Microvolt T‐Wave Alternans in High‐Risk Patients with the Congenital Long‐QT Syndrome

Background: Microvolt T‐wave alternans (MTWA) has been used for arrhythmogenic risk stratification in cardiac disease conditions associated with increased risk of sudden cardiac death. Macroscopic T‐wave alternans has been observed in patients with congenital long‐QT syndrome (LQTS). The role of MTWA testing in patients with LQTS has not been established. Objective: To determine the diagnostic value of MTWA testing in high‐risk patients with LQTS. Methods and results: We assessed MTWA in 10 consecutive LQTS index patients who survived cardiac arrest or had documented torsade de pointes tachycardia and 6 first‐degree family members with congenital LQTS which had been genotyped in 13 of 16 subjects (7 index patients, 6 family members). No LQTS‐causing mutation was identified in 3 index patients with overt QT prolongation. MTWA was assessed during standardized bicycle exercise testing using the spectral method and yielded negative (n = 8) or indeterminate (n = 2) results in index patients, respectively. Similarly, all first‐degree family members tested MTWA negative except for one indeterminate result. Two genotype positive family members could not be tested (two children—4 and 9 years of age). Conclusion: In patients with congenital LQTS, free from structural heart disease and with a history of life‐threatening cardiac arrhythmias, assessment of MTWA does not yield diagnostic value. Hence, determination of MTWA in lower risk LQTS patients without spontaneous arrhythmic events is likely not to be useful for arrhythmia risk stratification.     

T‐cell‐rich B‐cell lymphoma of the spleen presenting with severe hypersplenism

We report a 19‐year‐old woman who was presented with B‐symptoms, massive splenomegaly, hepatomegaly and hypersplenism. She underwent diagnostic/therapeutic splenectomy. Microscopically, the spleen showed a vaguely micronodular and diffuse proliferation of lymphoid cells in the white pulp that also involved the red pulp. On immunohistochemical staining, this proliferation consisted predominantly of CD3⁺, CD7⁺ small T cells with the presence of a minor populat?on of CD15^?,CD30^?, CD20⁺ large atypical B cells. A liver biopsy also showed a similar morphology to that seen in the spleen. After splenectomy, only the pancytopenia improved. A combined immunochemotherapy regimen (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone) was utilized, which resulted in a complete remission.     

Point‐of‐care ultrasound with pocket‐size devices in emergency department

Point‐of‐care ultrasound is a useful tool for clinicians in the management of patients. Particularly in emergency department, the role of point‐of‐care ultrasound is strongly increasing due to the need for a rapid assessment of critically ill patients and to speed up the diagnostic process. Hand‐carried ultrasound devices are particularly useful in emergency setting and allow rapid assessment of patient even in prehospital setting. This article will review the role of point‐of‐care ultrasonography, performed with pocket‐size devices, in the management of patients presenting with acute onset of undifferentiating dyspnea, chest pain, and shock in emergency department.