Janusz Maciejewski

Th1/Th2 balance and CD45-positive T cell subsets in primary nephrotic syndrome

Abstract T cells are involved in the pathogenesis of nephrotic syndrome (NS). The aim of the study was to determine whether the activity of T-helper-1 (Th1) and T-helper-2 (Th2) cells and the distribution of the lymphocyte subsets, namely CD45RA+CD4+ (”naive” helper T cells, suppressor-inducer), CD45RA+CD8+ (”naive” suppressor T cells, suppressor-effector), CD45RO+CD4+ (”memory” helper T cells), are predictive for steroid sensitivity in children with primary NS. These parameters were assessed at the onset of disease, before initiation of steroid therapy. Two groups of NS children were retrospectively formed according to steroid sensitivity (SS) or resistance (SR). The activity of Th1 and Th2 cells was defined by the production of interleukin-2 (IL-2), interferon-γ, IL-4, and IL-10 in the supernatants of CD4+ T cell cultures activated with autologous monocytes presenting tetanus toxoid (TT). Peripheral lymphocyte subsets were determined using double- or triple-color flow cytometry. In SS children with NS we found a decreased proliferative response of CD4+ T cells to TT stimulation, cytokine synthesis indicating the predominance of Th2 activity, and an increased percentage of activated suppressor-inducer (CD45RA+ CD4+CD25+, 5.18±0.8, P<0.001) and suppressor-effector (CD45RA+CD8+CD25+, 2.05±0.6, P<0.01) cells, with the concomitant reduction of activated memory cells (CD45RO+CD4+CD25+, 0.2±0.1, P<0.001). In children with SRNS we found an increased proliferative response of CD4+ T cells to TT, a rise in activated memory (CD45RO+CD4+CD25+, 3.82±0.7, P<0.01) and suppressor-inducer peripheral T cells (CD45RA+ CD4+CD25+, 3.85±0.6, P<0.01), but a low percentage of activated suppressor-effector (CD45RA+CD8+ CD25+, 0.5±0.2, P<0.05) T cells. We conclude that prior to treatment the distribution of lymphocyte subpopulations in peripheral blood together with Th1 and Th2 cell activity provides a useful tool for evaluating the likelihood of steroid sensitivity in patients with primary NS.

Increased apoptosis of peripheral blood lymphocytes in children with nephrotic syndrome.

Abstract Nephrotic syndrome is accompanied by and probably related to abnormal T-lymphocyte function. Decreased stimulation of survival factors and increased levels of ”dead signals” may lead to the malfunction of many cells, including lymphocytes. In our study, we investigated the process of apoptosis within T cells in children with a first attack of nephrotic syndrome (NS). We found that the number of apoptotic T cells is greater in these patients than in both children in remission from NS and in controls. The percentage of annexin-V-fluorescein isothiocyanate (FITC)-positive CD3+ cells was 27.30± 12.13% in children with a first attack of NS, 19.22± 15.16% (P=0.006) in children in remission and 16.20± 6.13% (P=0.004) in controls. The percentage of annexin-V-FITC-positive CD3+CD4+ cells was 7.35±7.72% in children with a first attack of NS, 3.80±3.75% (P=0.0001) in children in remission and 3.82±2.01% (P=0.0002) in controls. We conclude that abnormal number and function of T lymphocytes found in NS patients may be related to an increased apoptotic rate of circulating lymphocytes.

Familial, recurrent haemolytic-uraemic syndrome with hypocomplementaemia

We read with interest the report by Bogdanovic et al. [1] on haemolytic-uraemic syndrome (HUS) associated with Aeromonas hydrophila enterocolitis. Since July 1987, we have assessed 82 children with typical HUS. Stool specimens from each child with HUS were tested for the presence of multiple pathogens including verotoxin-producing Escherichia coli, Salmonella, Shigella, CampyIobacter, Yersinia and A. hydrophila. Oxidase testing was routinely performed on all stool isolates. Forty-five (55%) children had E. coli 0157 : H7, 2 (2%) children had A. hydrophila, and 1 child (1%) had Campylobacter in the stool. We concur with Bogdanovic et al. [1] thatA, hydrophila should be added to the list of bacteria that may trigger an episode of typical (D+) HUS and that oxidase testing should be routinely performed on all stool isolates in patients with HUS. Wm. Lane M. Robson 1 Alexander K. C. Leung 1 Cynthia L. Trevenen 2 Departments of I Pediatrics and 2 Pathology University of Calgary Alberta Childrens Hospital 300, 10601 Southport Road SW Calgary, Alberta T2W 3M6 Canada

A prospective study to determine the significance of ventricular late potentials in children with mitral valvar prolapse

We aimed prospectively to determine the incidence of ventricular arrhythmias and ventricular late potentials in children with mitral valvar prolapse, and to assess whether signal-averaged electrocardiography could identify which such children were at high risk of developing ventricular tachycardia. In all, we examined 151 children with mitral valvar prolapse, at an age of 12.2 +/- 3.1 years, and 164 healthy subjects aged 12.3 +/- 3.7 years. All children underwent 24-hour ambulatory Holter monitoring and echocardiography. The children with mitral valvar prolapse were followed prospectively for a mean of 64 months. There was a significantly higher prevalence of ventricular arrhythmias in those with prolapse than in the controls (p < 0.0001). Runs of ventricular tachycardia were observed in 3 children with mitral valvar prolapse compared with one from the control group. Late potentials were more frequently observed in the children with mitral valvar prolapse than in those who were healthy (p < 0.0001), and also in those with prolapse suffering ventricular arrhythmias compared with those without ventricular arrhythmias (p < 0.02). During follow-up, 24 children with prolapsing mitral valves developed non-sustained ventricular tachycardia, giving a frequency of 3.1/100 subject-years. The sensitivity of late potentials was low, at 52%, for the identification of children with mitral valvar prolapse who developed ventricular tachycardia, although the specificity was high at 90%. This gave a positive predictive value of 50%, and a negative predictive value of 91%. We conclude that prolapse of the mitral valve predisposes to the development of ventricular arrhythmias and late potentials in children. An abnormal signal-averaged electrocardiogram is a specific, but not very sensitive, predictor for the development of ventricular tachycardia in such children.