Combined T- and B-cell activation in childhood steroid-sensitive nephrotic syndrome.
BACKGROUND
Growing evidence shows that steroid-sensitive nephrotic syndrome (SSNS) is the result of a primary T-cell disturbance and leads to secondary anatomical and functional, however, not to immunological glomerular changes. In addition, immunoglobulin abnormalities in SSNS indicate a role of B-cell involvement.


METHODS
We therefore analyzed T- and B-cell activation markers in children with SSNS at different stages of the disease including different treatment regimens by measuring the soluble IL-2 receptor (sCD25) and the soluble low-affinity IgE receptor (sCD23), respectively. Seventy-five patients with SSNS (median age 8.0, range 2.5 - 18 years) were studied, 33 in relapse (RL) including 21 patients relapsing during alternate-day steroids (RL-SD). Forty-two patients were studied in remission (RM; 14 off treatment and 28 on alternate-day steroids (RM-AD)) and 22 age-matched children served as controls.


RESULTS
Serum concentrations of sCD25 were increased in RL (113.6 +/- 19.5 micromol/l) compared to RM (79.8 +/- 8 micromol/l, p < 0.02) and controls (74.8 +/- 0.9 micromol/l, p < 0.02). Patients with RL-SD did not have elevated sCD25. In relapse, sCD25 was inversely correlated with age (R = -0.36, p < 0.04) and positively correlated with total IgG (R = 0.37, p < 0.04). Urinary excretion of sCD25 was also significantly elevated in RL of SSNS compared to RM and controls (71.2 +/- 11.9 micromol/g creatinine vs. 39.1 +/- 4.8 and 32.0 +/- 4.2 micromol/g, p < 0.05). Serum levels of sCD 23 were significantly elevated in RL (6.22 +/- 0.65 microg/l) compared to RM (3.1 +/- 0.83 microg/l, p < 0.02) and to controls (3.4 +/- 0.93 microg/l). The highest values, however, were found in RL-SD (7.8 +/- 1.7 microg/l) vs. untreated RL (p < 0.007) and RM-AD (p < 0.002). In untreated RL there was a significant correlation of sCD23 and total IgE (R = 0.67, p < 0.02) and in RL-SD with total IgG (R = 0.45, p < 0.05). sCD23 and sCD25 were not correlated with each other.


CONCLUSIONS
These data document parallel abnormalities of both CD23-mediated B as well as CD25-mediated T-cell activation and suggest that SSNS is not solely a disorder of T-cell dysfunction.
Kemper
M J
MJ
Pediatric Nephrology, University Children's Hospital, Hamburg, Germany. Markus.Kemper@kispi.unizh.ch
Meyer-Jark
T
T
Lilova
M
M
Müller-Wiefel
D E
DE
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D008213:Lymphocyte Activation / Q000502:physiology*; D009404:Nephrotic Syndrome / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism*; D011446:Prospective Studies; D017455:Receptors, IgE / Q000097:blood* / Q000187:drug effects; D015375:Receptors, Interleukin-2 / Q000097:blood* / Q000187:drug effects; D012008:Recurrence; D012074:Remission Induction; D013256:Steroids / Q000008:administration & dosage*
D007074:Immunoglobulin G; D017455:Receptors, IgE; D015375:Receptors, Interleukin-2; D013256:Steroids