We investigated whether serum levels of insulin growth factor-1 (IGF-1) and insulin growth factor binding protein-3 (IGFBP-3) are valuable in predicting clinical outcomes or are correlated with other laboratory findings in children with Henoch-Schönlein purpura (HSP).
We examined 27 children who were consecutively admitted to our hospital with HSP between January 2011 and February 2012. Blood tests (C-reactive protein, white blood cell count, platelet count, erythrocyte sedimentation rate, albumin, immunoglobulin A, complement C3, antineutrophil cytoplasmic antibody, IGF-1, IGFBP-3) and urine tests were performed upon admission. IGF-1 and IGFBP-3 were resampled in the recovery phase. Controls included 473 children whose IGF-1 and IGFBP-3 were sampled for evaluating their growth, at the outpatient department of pediatric endocrinology in our hospital. IGF-1 and IGFBP-3 were compared between the HSP children and controls, and between the acute and recovery phases in HSP children. The ability of these values to predict clinical outcomes including renal involvement was analyzed using bivariate logistic regression analysis (BLRA).
IGF-1 and IGFBP-3 were not different between the HSP children and controls (148.7±117.6 vs. 69.2±96.9,
We concluded that IGF-1 and IGFBP-3 do not predict clinical outcomes of HSP, including renal involvement, in this study.
The long term prognosis of Henoch-Schönlein purpura (HSP) is determined by the degree of renal involvement [
Yildiz B et al. [
Ru L et al. [
In the present study, we aimed to investigate whether serum levels of IGF-1 and IGFBP-3 have values worthy of predicting clinical outcomes or are correlated with other laboratory findings in HSP children.
This study included 27 children who were consecutively admitted to our hospital with HSP between January 2011 and Febrary 2012. The diagnostic criteria of HSP were as follows: palpable purpura (mandatory criterion) in the presence of at least one of the following four features: 1) diffuse abdominal pain, 2) any biopsy showing predominant IgA deposition, 3) arthritis or arthralgia (acute, any joint), and 4) renal involvement (any hematuria and/or proteinuria). The criteria of admission were as follow: severe abdominal pain, gastrointestinal bleeding, arthalgia with limitation of joint motion and joint swelling, or painful scrotal swelling. Intraveous methylprednisolone (1-2 mg/kg devided by three times) was administered on admission. Once one or two days after their critical symptoms were resolved, they discharged with oral prednisolone (solondo 1-1.5 mg/kg devided by three times), which was tapered off over 2-3 weeks. The dates of follow-up visit were one week, one month, and three months after discharge on schedule and urinalysis was done at every visit. Nephritis was defined by the presence of persistent microscopic hematuria at least more than three times, gross hematuria or association with proteinuria (urine protein to creatinine ratio >0.2).
Laboratory tests at admission included complete blood cell counts, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), serum albumin, blood urea nitrogen, serum creatinine, C3, serum IgA, antinuclear antibody, IGF-1, IGFBP-3, and urine analyses. At recovery phase when patients revisited after discharge, IGF-1 and IGFBP-3 were resampled. Written informed consent was obtained from parents of enrolled patients prior to blood tests. The CHA University Institutional Review Board approved this study including the consent procedure (CHA IRB No. BD 2011-136D).
Controls included 473 children among 581 children who sampled IGF-1 and IGFBP-3 for the evaluation of their growth at the outpatient department of pediatric endocrinology in our hospital from January 2008 to october 2015. One hundred eight of 581 children were excluded in order to match the mean age and sex ratio of controls with HSP patients. Their data were collected retrospectively.
All blood and urine data of HSP children were collected prospectively. The level of IGF-1 and IGFBP-3 were compared between HSP children and controls, and between acute and recovery phase in HSP children. Also, we investigated whether their levels were correlated with clinical presentations and those severity, and they could predict their clinical outcomes including nephritis.
All variables were presented as the mean±standard deviation., and continuous variables were analyzed using the student’s t-test. Qualitative variables and correlations were analyzed using the Pearson chi-squared test and Pearson correlation coefficient (two-tailed probability), respectively. Non-parametric variables were analyzed using Spearman’s rank correlation coefficient. To investigate the ability of IGF-1 and IGFBP-3 to predict a clinical outcome in children with HSP, bivariate logistic regression analysis (BLRA) was used. Statistical analysis was performed using SPSS statistics 20 (SPSS Inc, Chicago, IL). Statistical significance was defined as
The demographic characteristics of children with HSP were shown in
There was no difference in the mean age and sex ratio between HSP children and controls (72.5±31.5 months vs. 74.1±24.2 months,
Age of HSP children was positively correlated with the duration of steroid use and serum IgA (
Serum IGF-1 was positively correlated with IGFBP-3, serum hemoglobin, age, total period of persistent purpura, total duration of steroid use, and total duration of nephritis (
Serum IGFBP-3 was positively correlated with serum hemoglobin, serum albumin, age, and total duration of nephritis (
Follow-up sampling of IGF-1 and IGFBP-3 was done in 8 HSP patients.
By BLRA, no variable including IGF-1 and IGFBP-3 (
HSP is a common multisystemic type of vasculitis associated with IgA mediated immune reaction with yet incompletely understood pathogenesis. Vessel inflammation and endothelial injury caused by IgA mediated immune reaction characterized by excessive production of proinflammatory cytokines, including interleukin (IL)-1, IL-6, IL-8, and tumor necrosis factor (TNF)-α, are possibly involved in HSP pathogenesis as demonstrated in the etiology of HSP [
There have been no other known predictor of the poor prognosis as well as the development of HSPN in HSP patients, except IGF-1, IGFBP-3, and genetic susceptibility reported in a few articles on the literature search. In this study, by BLRA as well as correlation coefficient, the duration of AP before visit and serum IgA were significant predictors of the presence of proteinuria in HSP children.
IGF-1 is a polypeptide growth factor that plays a significant role in cellular growth and survival, regarding pathological states in particular [
Although the actual cause of the endothelial damage in HSP is not well known, increasing evidence suggests that the activated neutrophils injure endothelial cells through the generation of reactive oxygen species which has been implicated as likely candidates [
However, in this study, either IGF-1 or IGFBP-3 could not be a relavant factor to predict any clinical outcome including proteiuria or nephritis. Furthemore, the increase of these levels at recovery phase in HSP children was not significant. Therefore, IGF-1 and IGFBP-3 were not useful markers to predict clinical outcomes including renal involvement in HSP children.
Recently, Ge W et al. [
The present study has the following limitations: (1) the size of study population was small; (2) the severity of HSP nephritis in this study was milder than in other related studies; (3) the data of contol were collected retrospectively, and (4) there were no data of comparative laboratory findings in controls except IGF-1 and IGFBP-3.
In conclusion, IGF-1 and IGFBP-3 levels do not predict clinical outcomes of HSP, including renal involvement in this study.
Clinical Courses of Children with Henoch-Schölein Purpura (HSP), and Comparison of Insulin Growth factor-1 (IGF-1) and Insulin Growth Factor Binding Protein-3 (IGFBP-3) between Children with HSP and Controls
HSP | Control | ||
---|---|---|---|
N | 27 | 473 | |
Age (months) | 72.5±31.5 | 74.1±24.2 | 0.740 |
M:F | 13:14 | 231:242 | >0.05 |
Blood | |||
IGF-1 (ng/mL) | 148.7±117.6 | 169.2±96.9 | 0.290 |
IGFBP-3 (ng/mL) | 3,465.9±1,290.9 | 3,597.2±1,127.6 | 0.560 |
IgA (mg/dL) | 197.5±115.8 | ||
Complement 3 (mg/dL) | 139.2±30.7 | ||
CRP (mg/dL) | 1.1±1.5 | ||
Hgb (g/dL) | 12.8±1.1 | ||
Platelet (/mm3) | 375.3±117.6K | ||
Albumin (g/dL) | 4.2± 0.4 | ||
Clinical courses | |||
Ass. with prev. infection (N) | 14 | ||
Adm. duration (days) | 4.9±3.2 | ||
Steroid use (weeks) | 3.6±2.7 | ||
Follow-up (months) | 10.9±12.3 | ||
Purpura at adm. (N) | 27 | ||
Duration of purpura (weeks) | 3.5±5.4 | ||
Abd. pain at adm. (N) | 13 | ||
Duration of abd. pain before adm. (days) | 1.3±2.5 | ||
Arthralgia at adm. (N) | 17 | ||
Multiple joint involvement (N) | 5 | ||
Duration of arthralgia before adm. (days) | 1.5±2.7 | ||
Scrotal swelling (N) | 2 | ||
Nephritis (N) | 7 | ||
Treatment of nephritis (N) | 2 | ||
Duration of microscopic hematuria (months) | 2.78±8.3 | ||
c-ANCA positive (N) | 2 | ||
FANA positive (N) | 6 |
The laboratory examination results are expressed as mean and standard deviation.
Abbreviations: N, number of patients; M, male; F, female; CRP, C-reactive protein; Hgb, hemoglobin; K, x1,000; Ass. with prev. infection, associated with previous infection; Adm., admission; ANCA, anti-neutrophil cytoplasmic antibody; FANA, fluorescent antinuclear antibody test.
Follow-up of Insulin Growth Factor-1 (IGF-1) and Insulin Growth Factor Binding Protein-3 (IGFBP-3) in Henoch-Schönlein Purpura Children
At admission | Follow-up | ||
---|---|---|---|
Number of patients | 27 | 8 | |
IGF-1 (ng/mL) | 148.7±117.6 | 205.6±94.9 | 0.940 |
IGFBP-3 (ng/mL) | 3,465.9±1315.5 | 4,516.3±916.9 | 0.120 |
Interval between two samples (days) | 43.6±17.7 |
The laboratory examination results are expressed as mean±standard deviation.
The Results of Bivariate Logistic Regression Analyses for Insulin Growth Factor (IGF-1) and Insulin Growth Factor Binding Protein-3 (IGFBP-3) to Predict Clinical Outcomes in Children with Henoch-Schölein Purpura
IGF-1 |
IGFBP-3 |
|||
---|---|---|---|---|
OR | OR | |||
Previous viral infection | 0.163 | 0.994 | 0.059 | 0.999 |
Abdominal pain (AP) | 0.939 | 1.000 | 0.595 | 1.000 |
Arthralgia | 0.130 | 0.994 | 0.208 | 1.000 |
AP+arthralgia | 0.162 | 0.990 | 0.266 | 1.000 |
Multiple joint involvement | 0.345 | 0.993 | 0.293 | 0.999 |
Hematochezia | 0.448 | 0.994 | 0.507 | 1.000 |
Nephritis | 0.221 | 1.005 | 0.142 | 1.000 |
AP+arthralgia+nephritis | 0.390 | 0.991 | 0.735 | 1.000 |
Proteinuria | 0.906 | 1.001 | 0.572 | 1.000 |