Major histocompatibility complex antigens in steroid-responsive nephrotic syndrome

An increased frequency of specific major histocompatibility complex (MHC) class I, II and III antigens in children with steroid-responsive nephrotic syndrome (SRNS) has been reported. This frequency distortion, in some cases, is thought to affect the outcome of the disorder. We studied the phenotypic frequency of HLA antigens-A,-B, and-DR, as well as complement proteins Bf and C4 in an unrelated population of 25 SRNS children. Complete MHC haplotypes were also derived for four families in which 8 individuals developed SRNS. HLA-DR8, with a relative risk of 4.8, showed the strongest association with SRNS. Nonetheless, the 95% confidence intervals of this and the relative risks for all other antigens fell below 1.0. No common haplotype was found in SRNS patients in whom complete family studies were available, and disease and inheritance of the MHC were discordant in two of these families. In this study of well-characterized SRNS patients we were unable to discover a clear association between this disorder and the MHC.     

Atopy,serum IgE,and interleukin-13 in steroid-responsive nephrotic syndrome

Earlier studies have demonstrated a strong association of steroid-responsive nephrotic syndrome (SRNS), atopy, and elevated serum IgE levels. Interleukin (IL-13) gene expression is significantly increased in children with SRNS in relapse. As interferon (IFN)-, IL-13, and IL-4 have regulatory effects on IgE synthesis, we examined the relationship between intracellular cytokine production and serum IgE levels in children with SRNS, in order to further define the reported association with atopy. The median serum IgE levels in nephrotic patients in relapse with (492 U/ml) or without atopy (561 U/ml) were significantly higher than those in remission (221 U/ml, P<0.002 or 90 U/ml, P<0.001, respectively) and non-atopic controls (177 U/ml) (P<0.001). The percentage of CD3+ IL-13-producing cells was significantly higher in nephrotic children in relapse, and correlated with the serum IgE levels during the active phase of the disease (r=0.90, P<0.001). These data suggest that the elevated serum IgE levels during relapses of SRNS were the result of upregulation of IL-13. This probably reflects some common immune activation following various stimuli, rather than a direct association with atopy.     

Familial steroid-responsive nephrotic syndrome and HLA antigens in Bengali children

We investigated the major histocompatibility complex class I and II loci in three Bengali families with nine children affected with steroid-sensitive nephrotic syndrome (SSNS). A sequence-specific primer (SSP) of DNA typing method was used to detect human leukocyte antigens (HLA). The unaffected siblings and their parents were also studied. Similar to previous reports, there was a high frequency of HLA-DR7.1 (DRB1*0701), DR53 (DR B4*01011-0104) and DQ2 (DQB2*0201-3) antigens in the affected children. However, there was a similar finding in the unaffected children and their parents. HLA-DR7.1 probably was not a causative factor, since it had no predictive value for the occurrence or the severity of SSNS in the affected families. Siblings with identical HLA typing behaved differently (they either had or did not have SSNS). In these families there was no correlation between predisposition to the nephrotic syndrome and the genetic determinant responsible for HLA.     

Increased HLA-A*11 in Chinese children with steroid-responsive nephrotic syndrome

Human leukocyte antigen (HLA) associations have been frequently reported in childhood steroid-responsive nephrotic syndrome (SRNS) in other populations. The aim of this study was to characterize the immunogenetic background of Singaporean Chinese patients with childhood SRNS. We determined the HLA class I (HLA-A* and HLA-B*) as well as class II (HLA-DRB1*, HLA-DQB1*) gene polymorphisms using the polymerase chain reaction-sequence specific oligonucleotide (PCR-SSO) technique, in patients with SRNS (n=64) and normal controls (n=236 for HLA-A*, n=80 for HLA-B*, HLA-DRB1* and HLA-DQB1*). The frequency of HLA-A*11 allele was significantly higher in the SRNS patients compared to controls (78.1% vs 54.2%, respectively; relative risk, RR=3.01, Pc=0.011). However, there was no significant difference in the allele frequencies of HLA-B*, HLA-DRB1* and HLA-DQB1* between the SRNS patients and controls, unlike that in previous studies. Our data suggest that the immunogenetic background of Singaporean Chinese with childhood SRNS was different from that in other populations. As HLA-A*11 has been strongly associated with other autoimmune diseases, it is conceivable that the HLA-A*11-specific motif may play a role in the development of the abnormal T-cell-mediated immune response that may be responsible for triggering the proteinuria seen in SRNS. Received: 24 April 2001 / Revised: 14 November 2001 / Accepted: 18 November 2001     

家族性激素反应性肾病综合征一家系报告及文献复习

目的 报道家族性激素反应性肾病综合征，分析其临床病理特点及家族发病的特点，及其与NPHS2基因的关系。方法 分析患者临床及病理表现特点，并对其家族成员患病情况进行调查；与文献报告的家族性激素反应性肾病综合征对比。运用高效液相色谱(DHPLC)的方法检测该家系NPHS2基因突变。结果 该家族的患病情况符合文献报告的家族性激素反应性肾病综合征的定义，临床表现为肾病综合征，病理改变为肾小球微小病变，对足量的强的松治疗反应敏感，易复发，但发病年龄较国际上报道的中位年龄高。同国外同类报道一样，该家族中未发现NPHS2突变。结论 首次在国内报告家族激素反应性肾病综合征。该疾病在此家系中的发生与NPHS2无明显关系.     

Long-term linear growth of children with severe steroid-responsive nephrotic syndrome

The present study was designed to evaluate the risk of permanent linear growth impairment in a selected group of 42 children with steroid-dependent nephrotic syndrome (SDNS) and 14 children with frequently relapsing nephrotic syndrome (FRNS). Longitudinal height measurements were available in all patients from the onset of the disease for a mean follow-up of 11.7±3.5 years. During the prepubertal period, patients lost 0.49±0.6 height SD score (HtSDS) (P<0.001). Twenty-three patients have reached their final height with an average loss of 0.92±0.8 HtSDS from the onset of their disease (P<0.001) and 0.68±0.7 from their target HtSDS (P<0.001). The pubertal growth spurt was mildly delayed in male but not female patients. Steroid therapy, calculated as the mean duration of prednisone (PDN) treatment or as the average cumulative PDN dose, was the only predictor of poor growth evolution. Partial catch-up growth occurred after PDN withdrawal. Children with early onset NS and adolescent patients, who were still receiving PDN after the age of 9 years in girls and 11 years in boys, were at higher risk for HtSDS loss. In conclusion, children with severe steroid-responsive NS are at risk of permanent growth retardation secondary to prolonged courses of steroid treatment.     

Urotensin-II levels in children with minimal change nephrotic syndrome

Human urotensin-II (hU-II) is the most potent mammalian vasoconstrictor identified to date. Although it is expressed mainly in the brain and spinal cord, it is also detected in other tissues, such as the kidney. It has been speculated that U-II might be an important physiological mediator of vascular tone and blood pressure in humans. To our knowledge, no studies have investigated the level of U-II in children with minimal change nephrotic syndrome (MCNS). Considering the renal synthesis and vasoactive role of U-II, we aimed to measure the plasma and urinary levels of U-II in children with MCNS, and investigate the correlation with other clinical and laboratory findings. Twenty-six children with clinical MCNS, ranging in age from 2 to 7 years, were compared with 16 healthy age- and sex-matched controls. The median age of the children was 4.73±2.36 years. U-II level was measured by RIA. Plasma U-II concentrations (pg/ml) were decreased during relapse (20.11±14.43 in relapse, 38.94±23.86 in remission, P <0.05), whereas urinary U-II levels (pg/mg urinary creatinine) were significantly higher in relapse than in remission (37.31±28.43 in relapse, 31.09±21.10 in remission, P <0.05). We could not detect any relationship between U-II levels and other clinical and laboratory parameters. Our data indicate that the important changes in plasma and urinary U-II levels during relapse may be the result of heavy proteinuria rather than playing a role in mediating the clinical and laboratory manifestations of MCNS in children.