Serum VEGF-A and VEGFR-1 levels in patients with adult immunoglobulin A vasculitis.

AIM: Immunoglobulin A vasculitis (IgAV) is classified as a leukocytoclastic vasculitis characterized by immune deposits in endothelial walls of small vessels causing vascular endothelial injury. The aim of the present study is to evaluate levels of vascular endothelial growth factor-A (VEGF-A) and VEGF receptor-1 (VEGFR-1) levels in adult IgAV patients. METHOD: Thirty-seven adult IgAV patients admitted to the Rheumatology Clinic meeting the IgAV American College of Rheumatology (ACR) criteria and 32 control subjects were enrolled in the study. Disease activity was categorized as "remission" or "active" according to Birmingham Vasculitis Activity Score (BVAS). Serum VEGF-A, VEGFR-1 levels and VEGFR-1/VEGF-A ratio were evaluated in patient and control groups. RESULTS: Serum median VEGF-A, VEGFR-1 and VEGFR-1/VEGF-A ratios were significantly higher in the patient group when compared to controls (235.9 [155-308.4] pg/mL vs. 78.8 [29.7-210.3] pg/mL, 400 [277.2-724.3] pg/mL vs. 31.5 [12.5-214.4] pg/mL and 1.85 [0.57-2.97] vs. 0.46 [0.38-0.63] respectively, all P values <.001). VEGFR-1 had the strongest predictive value with a cut-off value of 0.6 with 75% sensitivity and 73% specificity (P < .001). CONCLUSION: This study is the first report indicating elevated serum VEGF-A, VEGFR-1, and more importantly VEGFR-1/VEGF-A ratio can be good representatives of the inflammatory processes together with vascular endothelial injury in adult IgAV patients. VEGFR-1 seems to be a more important indicator of the ongoing inflammation.

Serum levels of galactose-deficient IgA1 in Chinese children with IgA nephropathy, IgA vasculitis with nephritis, and IgA vasculitis.

OBJECTIVE: IgA nephropathy (IgAN) and IgA vasculitis with nephritis (IgAV-N) are related diseases. Galactose-deficient IgA1 (Gd-IgA1) plays an important role in the pathology of IgAV-N and IgAN, so we aim to compare the serum levels of Gd-IgA1 in Chinese pediatric patients with IgAN, IgAV-N, and IgAV. METHODS: We retrospectively enrolled 52 patients with IgAN, 57 patients with IgAV-N, 26 patients with IgAV, and 40 healthy children. The serum levels of Gd-IgA1 were measured at the time of biopsy using a lectin-based ELISA method. RESULTS: Gd-IgA1 levels in IgAV-N patients and IgAN patients were higher than in healthy controls (303.94 ± 39.37 U/ml, 314.91 ± 47.79 U/ml vs. 273.57 ± 48.29 U/ml, P < 0.001), and Gd-IgA1 levels in IgAV-N patients were higher than in IgAV patients (303.94 ± 39/ml vs. 286. 21 ± 38.81 U/ml, P = 0.059), but the latter result is not statistically significant. The Gd-IgA1 levels in IgAV patients were comparable with those in healthy controls (286.21 ± 38.81 U/ml vs. 273.57 ± 48.29 U/ml, P = 0.267). Among the four groups, we did not observe significant correlations of Gd-IgA1 levels with eGFR, proteinuria, or the MEST-C score. CONCLUSION: Serum Gd-IgA1 maybe involved in the pathogenesis of the IgAV-N and IgAN. However, we found no statistically significant correlation between Gd-IgA1 levels and clinical and pathological features.

Analysis of the association between kidney injury biomarkers concentration and nephritis in immunoglobulin A vasculitis: A pediatric cohort study.

OBJECTIVE: The aim of this study was to investigate the clinical course, selected biochemical parameters and concentrations of renal injury biomarkers such as neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1) and liver-fatty acid binding protein (L-FABP) in patients with immunoglobulin A vasculitis (IgAV) to identify the markers associated with nephritis in the course of the disease (IgAVN). METHODS: The study involved 29 children with IgAV and 34 healthy controls. Eleven (38%) patients had renal involvement (IgAV-N) and 18 (62%) did not exhibit nephritis (IgAV-noN). Initial laboratory tests, determining the concentrations of NGAL, KIM-1 and L-FABP in serum and urine, were conducted on children from the study group in an acute phase of IgAV as well as after an average of 6 months, during a follow-up visit. The interconnection between renal involvement, anthropometric measurements, epidemiological data, laboratory parameters and levels of examined biomarkers have been thoroughly evaluated. RESULTS: The serum and urine levels of NGAL, KIM-1 and L-FABP were significantly higher in children with an acute phase of IgAV as compared to the control group (P < .001) and markedly lower during follow-up retesting in comparison with the values obtained at inclusion (P < .001). However, the concentration of none of the evaluated biomarkers correlated with nephrological indices. Among all examined parameters, only male subjects were associated with nephritis (P = .017). CONCLUSIONS: We have established no evident association between the concentrations of NGAL, KIM-1 and L-FABP and nephritis in the course of IgAV in children. Additionally, we confirmed a significant male predominance in patients with nephritis.

Procalcitonin and C-reactive Protein Levels as Biomarkers to Determine Gastrointestinal Involvement in Adult Henoch-Schönlein Purpura Patients.

OBJECTIVE: To investigate the association of procalcitonin (PCT) and C-reactive protein (CRP) levels with gastrointestinal (GI) involvement in adult HSP patients. METHOD: A retrospective study using clinical data and serum PCT and CRP levels from 121 adult HSP patients was performed. RESULTS: The proportion of male HSP patients with GI involvement was significantly higher compared to patients without GI involvement. PCT and CRP levels in adult HSP patients with GI involvement were higher compared to patients without GI involvement (P < 0.05); Among the patients with GI involvement, those with GI hemorrhage had significant higher PCT and CRP levels (P < 0.05); the median PCT value was lower compared to the threshold value for systemic infection. There was a positive correlation between PCT and CRP levels in HSP patients with GI involvement and GI bleeding (P < 0.05). ROC curve analysis demonstrated that the PCT and CRP cutoff levels of 0.07 ng/ml and 29.35 mg/L respectively had optimal diagnostic efficacy for GI bleeding in adult HSP patients. CONCLUSION: Elevated serum PCT and CRP levels were significantly associated with GI involvement in adult HSP patients, especially for GI bleeding. PCT levels correlated well with CRP levels.

A cross-sectional analysis of clinicopathologic similarities and differences between Henoch-Schönlein purpura nephritis and IgA nephropathy.

INTRODUCTION: Recent studies noted that Henoch-Schönlein purpura nephritis (HSPN) and IgA nephropathy (IgAN) share the feature of galactose-deficient IgA1 (Gd-IgA1)-oriented pathogenesis, although there are distinct clinical differences. We aimed to clarify the clinicopathologic differences between these 2 diseases. METHODS: We cross-sectionally analyzed adult patients with HSPN (n = 24) or IgAN (n = 56) who underwent renal biopsy (RB) between 2008 and 2018 at Showa University Hospital. Serum Gd-IgA1 (s-Gd-IgA1) levels at the time of RB were compared among study groups using enzyme-linked immunosorbent assay (ELISA) with anti-human Gd-IgA1-specific monoclonal antibody (KM55). We also immunohistochemically stained paraffin-embedded sections for glomerular Gd-IgA1 (g-Gd-IgA1)-deposition using KM55. Serum inflammatory cytokines were measured using ELISA. RESULTS: Glomerular endothelial injury with subendothelial IgA deposition was significant in patients with HSPN. Serum IL-8, MCP-1, TNF-α, and IL-6 levels were significantly higher in patients with HSPN than IgAN. Levels of s-Gd-IgA1 were comparable among patients with HSPN and IgAN, and a similar degree of g-Gd-IgA1-deposition was detected in both diseases. Furthermore, g-Gd-IgA1-deposition was evident in patients with histopathologically advanced HSPN or IgAN. In HSPN, significant positive correlations between s-Gd-IgA1 levels and crescent formation or IL-6 elevation were confirmed, and g-Gd-IgA1 intensity showed a significant positive correlation with MCP-1 and a tendency to positively correlate with IL-8. Meanwhile, patients with IgAN showed no correlation between inflammatory cytokines and both-Gd-IgA1. Moreover, most g-Gd-IgA1-positive areas were not double stained with CD31 in HSPN. CONCLUSIONS: Although assessing both-Gd-IgA1 alone was insufficient to distinguish between HSPN and IgAN, patients with HSPN showed considerable glomerular capillaritis with subendothelial IgA deposition and significant elevation of serum inflammatory cytokines. Furthermore, such glomerular subendothelial IgA deposition might not contain Gd-IgA1, and factors associated with Gd-IgA1 were inconsistent among these 2 diseases. Thus, developmental mechanisms for IgAN might not apply to HSPN completely, and these 2 diseases still have different aspects.

Función predictiva del índice de neutrófilos/linfocitos y del volumen plaquetario medio en la púrpura de Henoch-Schönlein relacionada con compromiso renal y gastrointestinal / Predictive role of neutrophil to lymphocyte ratio and mean platelet volume in Henoch-Schönlein purpura related gastrointestinal and renal involvement

Antecedentes: La púrpura de Henoch-Schönlein (PHS) es una vasculitis sistémica de vasos pequeños. El objetivo fue evaluar el índice de neutrófilos/linfocitos (INL) en sangre y el volumen plaquetario medio (VPM) en la PHS e investigar la relación con el compromiso renal y gastrointestinal.Métodos: Se incluyeron niños con PHS y controles sanos. Se evaluaron concentración de hemoglobina, recuento de leucocitos, recuento de trombocitos, INL, VPM, velocidad de sedimentación globular y proteína C-reactiva.Resultados: El INL fue significativamente mayor en los pacientes con PHS con hemorragia gastrointestinal (p < 0,001). El valor ideal de corte del INL para predecir la hemorragia gastrointestinal fue 2,05, con 93 % de sensibilidad y 62 % de especificidad. El VPM fue significativamente mayor en los pacientes con PHS con compromiso renal (p = 0,027).Conclusiones: El INL en sangre y el VPM podrían ser útiles para identificar el compromiso renal y gastrointestinal en la PHS

Background: Henoch-Schönlein purpura (HSP) is a systemic small-vessel vasculitis that occurs mainly in children. The aim was to evaluate the blood neutrophil-to-lymphocyte ratio (NLR) and mean platelet volume (MPV) in patients with HSP and to investigate the relationship with gastrointestinal and renal involvement.Methods: Children with HSP and healthy individuals as controls were included. Hemoglobin level, white blood cell count, platelet count, NLR, MPV erythrocyte sedimentation rate and C-reactive protein were evaluated.Results: There were 71 HSP children and 74 controls. NLR was significantly higher in HSP patients with gastrointestinal bleeding than without gastrointestinal bleeding (p < 0,001). The optimal cutoff value of NLR for predicting gastrointestinal bleeding was 2.05, with 93 % sensitivity and 62 % specificity. MPV was significantly higher in HSP patients with renal involvement than without renal involvement (p = 0,027).Conclusions:Blood NLR and MPV may be useful markers to identify gastrointestinal and renal involvement in HSP patients.

Hemotologic Indices for Predicting Internal Organ Involvement in Henoch-Schönlein Purpura (IgA vasculitis).

Henoch-Schönlein purpura is the most common vasculitis of childhood. This study investigated the values of hematologic indices that can help predict internal organ involvement. The study included 112 patients followed up between January 2007 and May 2017 and 81 healthy children. Leukocyte, neutrophil, monocyte, lymphocyte and platelet counts, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and C-reactive protein (CRP) levels were compared between patients with and without internal organ involvement. Overall, 57 (50.8%) patients had internal organ involvement. Leukocyte, neutrophil, and monocyte counts, NLR, and CRP levels were significantly higher in patients with internal organ involvement than in patients without internal organ involvement. There was no difference between the groups in terms of lymphocyte count, platelet count, and PLR. The cutoff values were found to be ≥10.8×10/L [area under the curve (AUC), 0.734] for leukocyte, ≥6.0×10/L (AUC, 0.665) for neutrophil, ≥0.710×10/L (AUC, 0.681) for monocyte, ≥3.95×10/L (AUC, 0.609) for NLR, and 2.41 mg/dL (AUC, 0.635) for CRP. Logistic regression analysis revealed that leukocyte count is a risk factor for internal organ involvement. Leukocyte, neutrophil, monocyte counts, NLR, and CRP levels are useful in predicting internal organ involvement in the acute phase of Henoch-Schönlein purpura. Leukocyte count is an important risk factor for internal organ involvement and its predictive value is more reliable than the other hematologic indices.

Changes of inflammatory mediators and oxidative stress indicators in children with Henoch-Schönlein purpura and clinical effects of hemoperfusion in the treatment of severe Henoch-Schönlein purpura with gastrointestinal involvement in children.

BACKGROUND: To explore the changes of inflammatory and oxidative stress responses in Henoch-Schönlein purpura (HSP) children, and further analyzed the therapeutic effects and mechanisms of hemoperfusion (HP) on HSP with severe gastrointestinal (GI) involvement. METHODS: There were 200 children with HSP were divided into three groups according to their clinical manifestations: 60 in HSP without GI and renal involvement group, 60 in HSP with GI involvement group, and 80 in HSPN group. The HSP with GI involvement group was subdivided into conventional treatment (n = 30) and HP (n = 30) groups. Thirty children who visited the department of children healthcare for healthy physical examinations from January to December 2017 were set as healthy control group. The IL-6 and TNF-α levels were detected by chemoluminescence method. The MDA, SOD and T-AOC levels were determined by thiobarbituric acid colorimetric method, hydroxylamine method and chemical colorimetry. RESULTS: Compared with healthy group, IL-6, TNF-α and MDA levels in HSP were increased in each group, while SOD and T-AOC were decreased (P = 0.000). IL-6, TNF-α and MDA levels in the HSPN group were the highest, SOD and T-AOC levels were the lowest (P = 0.000). Compared with those before treatment, IL-6, TNF-α and MDA levels in the conventional and HP groups were decreased and SOD and T-AOC levels were increased (P = 0.000). The changes in HP group were more significant than those in conventional group (P < 0.047). Compared with conventional group, glucocorticoid dosage and the occurrence rate of hematuria and/or proteinuria within 3 months were lower in HP group. (P = 0.000, 0.004). CONCLUSIONS: Inflammatory and oxidative stress may be involved in the acute phase of HSP children. The intensity of inflammatory and oxidative stress responses were related to the degree of renal involvement. HP can reduce glucocorticoid dosage and the rate of renal involvement in children with severe HSP with GI involvement. The mechanism may be related to the fact that HP can effectively remove IL-6, TNF-α, MDA in HSP children.

Do practical laboratory indices predict the outcomes of children with Henoch-Schönlein purpura?

Objectives: Henoch Schönlein Purpura (HSP) is the most common systemic vasculitis of childhood and often has a self-limiting course. We aimed to study whether practical laboratory parameters at the diagnosis predict disease course including recurrence and nephritis in addition to severe gastrointestinal involvement in children with HSP. Methods: This retrospective cohort study included 214 HSP patients, 43.5% (n = 93) female and 56.5% (n =121) male, who were diagnosed in our department. Laboratory parameters before treatment, including neutrophil, lymphocyte and platelet counts, mean platelet volume (MPV), neutrophil-to-lymphocyte (NLR), and platelet-to-lymphocyte ratios (PLR) were obtained retrospectively. Age at diagnosis, duration of follow-up, gender, preceding infections, medications, arthritis and arthralgia, abdominal pain, severe GI involvement, invagination, renal involvement and presence of nephritis, outcomes, and presence of recurrences were retrospectively recorded from medical files. Severe GI involvement was determined as severe colicky abdominal pain, bowel edema in ultrasonography or overt GI bleeding. A relapse was defined as a new flare of cutaneous lesions or other manifestations in a patient at least four asymptomatic weeks after the initial HSP episode. Results: Mean age at diagnosis was 7.6 ± 3.1 years. Biopsy-proven nephritis was found in 16 (7.5%) patients. Severe GI involvement was present in 77 (36%) patients, whereas only 12 (5.6%) patients were diagnosed with intussusception and in 29 (13.5%) patients, HSP recurred. Neutrophil count and NLR were found higher in HSP patients with severe gastrointestinal involvement and biopsy-proven nephritis. Additionally, only platelet count was lower and MPV was higher in patients with recurrent HSP. Conclusion: Elevated neutrophil count and NLR may be relevant markers for severe GI involvement and nephritis, whereas platelet count and MPV were the only laboratory parameters associated with disease recurrence.

Significance of histological crescent formation in patients with IgA vasculitis (Henoch-Schönlein purpura)-related nephritis: a cohort in the adult Chinese population.

BACKGROUND: IgA vasculitis (IgAV, formerly Henoch-Schönlein purpura) is a type of systemic vasculitis. This study aimed to explore the clinicopathological features, treatment and renal outcomes of adult IgAV-related nephritis (Henoch-Schönlein purpura nephritis) patients with different degrees of crescent formation. METHODS: Adult patients with biopsy-proven IgAV-related nephritis in Nanjing Jinling Hospital were enrolled and divided into three groups as follows: control (no crescents, n = 257), group 1 (crescents < 25%, n = 381), and group 2 (crescents ≥25%, n = 60). The clinicopathological features, treatment and renal outcomes were compared among the three groups. RESULTS: There were no significant differences in gender and age at biopsy among the three groups. Groups with more crescents had shorter renal durations and higher prevalence of macroscopic hematuria, proteinuria and nephrotic syndrome than the control group. The presence of renal insufficiency at biopsy was similar, whereas laboratory findings indicated that patients with ≥25% crescents had higher levels of serum creatinine and blood urea nitrogen than the control and group 1. Histologically, the incidence of glomeruli-Bowman's capsule adhesion and capillary necrosis were proportional to the degree of crescent formation. Patients with more crescents received more positive immunosuppressive therapies. During follow-up, the levels of proteinuria and hematuria were in remission after treatment, and patients without crescents had lower levels of proteinuria. At the last follow-up, the renal function had deteriorated in the control and group 1, whereas the levels of serum creatinine at biopsy and last follow-up were similar in group 2. There was a significant difference in renal survival from end-stage renal disease (ESRD) or 50% decline in renal function among the three groups (log-rank, P = 0.030). However, no association between crescent formation and renal outcomes was found after adjusting potential confounders. CONCLUSIONS: Adult IgAV-related nephritis patients with more crescents had more-severe renal manifestations and worse treatment responses, whereas the proportions of crescents were not associated with higher risks for ESRD or 50% decline in renal function. A more suitable pathological classification standard is needed to predict renal prognosis.

Clinical significance of serum and mesangial galactose-deficient IgA1 in patients with IgA nephropathy.

INTRODUCTION: Galactose-deficient IgA1 (Gd-IgA1) is a critical pathogenic factor for IgA nephropathy (IgAN), but its value as a disease-specific biomarker remains controversial. We aimed to clarify the clinical significance of Gd-IgA1 in patients with IgAN. METHODS: We retrospectively reviewed 111 patients who were diagnosed with IgAN based on the findings of renal biopsies (RB) at Showa University Hospital since 2007. Serum Gd-IgA1 (s-Gd-IgA1) at the time of RB was compared among 111 IgAN patients, 18 Henoch-Schönlein purpura nephritis (HSPN) patients, 29 lupus nephritis (LN) patients, 28 ANCA-associated vasculitis (AAV) patients, and 13 minimal change disease (MCD) patients using ELISA with an anti-human Gd-IgA1-specific monoclonal antibody (KM55). We also immunohistochemically stained paraffin-embedded sections for mesangial Gd-IgA1 (m-Gd-IgA1) deposition using KM55. RESULTS: Although levels of s-Gd-IgA1 were comparable among IgAN and HSPN, s-Gd-IgA1 levels were significantly elevated in patients with IgAN compared with LN, AAV and MCD (IgAN vs. HSPN, LN, AAV, and MCD: 16.2 ± 9.1 vs. 14.2 ± 10.8, p = 0.263; 12.7 ± 9.4, p = 0.008; 13.1 ± 7.3, p = 0.059; and 8.2 ± 4.8 µg/mL, p<0.001, respectively). Mesangial-Gd-IgA1 deposition was specifically detected in IgAN or HSPN. The increase in s-Gd-IgA1 significantly correlated with m-Gd-IgA1 positivity in patients with IgAN, and s-Gd-IgA1 elevation and m-Gd-IgA1 deposition were evident in patients with histopathologically advanced IgAN. Moreover, s-Gd-IgA1 levels were significantly higher in IgAN patients with glomerular sclerosis and tubulo-interstitial lesions. Mesangial-Gd-IgA1 intensity negatively correlated with eGFR in IgAN. Multivariate analysis selected s-Gd-IgA1 elevation as a significant risk factor for a 30%-reduction in eGFR in IgAN (HR, 1.37; 95% CI, 1.02-1.89; p = 0.038). CONCLUSIONS: Although IgAN and HSPN remain difficult to differentiate, s-Gd-IgA1 elevation and m-Gd-IgA1 deposition are reliable diagnostic factors that reflect IgAN severity. Serum-Gd-IgA1 could serve as a predictor of renal outcomes in IgAN. Thus, Gd-IgA1 could be significant biomarker for patients with IgAN.

Clinical significance of the serum biomarker index detection in children with Henoch-Schonlein purpura.

OBJECTIVE: To explore a panel of serum biomarkers for laboratory diagnosis of pediatric Henoch-Schönlein purpura (HSP). METHODS: The blood white blood cells (WBC) and serum levels of serum amyloid A (SAA), interleukin 6 (IL-6), immunoglobulin A (IgA), immunoglobulin G (IgG), immunoglobulin M (IgM), immunoglobulin E (IgE), C-reactive protein (CRP), complement component 3 (C3), complement component 4 (C4), and ASO (anti-streptolysin O) were detected in 127 patients with Henoch-Schonlein purpura (HSP), 110 cases of septicemia patients, and 121 healthy volunteers. The diagnostic ability of biomarkers selected from HSP and septicemia patients was analyzed by ROC curve. By designing the calculation model, the biomarker index was calculated for laboratory diagnosis of HSP and differential diagnosis between HSP and septicemia. RESULTS: The levels of serum WBC, CRP, IL-6 and SAA in the septicemia patients were significantly higher than those in the control group (p<0.05). Compared with the healthy individuals, serum levels of WBC, CRP, IL-6, SAA, IgA and IgM were significantly increased in patients with HSP (p<0.05). The area under the curve (AUC) of SAA, IgA, IgM, WBC, IL-6, and CRP in the patients with HSP was 0.964, 0.855, 0.849, 0.787, 0.765, and 0.622, respectively. The values of SAA, IgA, IgM, WBC, IL-6, and CRP in septicemia patients were 0.700, 0.428, 0.689, 0.682, 0.891, and 0.853, respectively. Biomarker index=SAA+IgA/4000+IgM/4000×0.4CRPmean valueCRPi. The biomarker index in HSP patients was significantly higher than that of the healthy controls. However, the biomarker index in septicemia patients was significantly lower than the control. CONCLUSION: The biomarker index of HSP patients is higher than that of the control group. While in the infectious disease represented by septicemia, it is decreased. The detection of biomarker index could exclude the interference of infection as the auxiliary examination to HSP patients.

A single-center analysis of Henoch-Schonlein purpura nephritis with nephrotic proteinuria in children.

BACKGROUND: In children with Henoch-Schonlein purpura nephritis (HSPN), the degree of proteinuria has been proven to be not only a sign of kidney damage, but also an accelerator of kidney disease progression. Nephrotic proteinuria at disease onset has been proposed as a predictor of a poor renal outcome. This study aims to assess the clinical and pathological features of HSPN with nephrotic proteinuria in a single center. METHODS: One hundred thirty-seven patients with HSPN who visited Shanghai Children's Hospital from January 2009 to December 2013 were retrospectively reviewed. The patients were divided into 2 groups based on the 24-h urinary protein levels: nephrotic proteinuria group (NP group: 24-h urinary protein ≥50 mg/kg) and non-nephrotic proteinuria group (NNP group: 24-h urinary protein <50 mg/kg). In addition, data regarding their sex, age, clinical features, renal pathology, and prognosis were collected. RESULTS: (1) There were 34 boys and 20 girls in the NP group with a mean age of 8.39 ± 2.85 years. The peak age of incidence was 6 to 11 years (72.22%). (2) There were 8 cases (14.81%) with joint symptoms and 9 cases (16.67%) with gastrointestinal symptoms in the NP group. According to the analysis of the laboratory test results, the serum albumin and IgG levels of the NP group were significantly lower than that of the NNP group (35.04 ± 8.45 in the NP group vs. 41.55 ± 4.46 in the NNP group, P < 0.0001; 7.68 ± 3.12 in the NP group vs. 9.53 ± 2.74 in the NNP group, P < 0.001, respectively); their blood urea nitrogen and cystatin C levels increased significantly (P < 0.05). (3) The majority of the pathological changes in the NP group were above the International Study of Kidney Disease in Children (ISKDC) grade III (62.97%). The NP group patients with tubulointerstitial injurie with grade 2 and above (50%) were prioritized. Immune complex deposition in the NP group was dominated by IgA. (4) The prognosis of the NP group was in complete remission (A), and their cases did not develop into end-stage renal disease; their prognosis was also associated with clinical classification (P < 0.01) but was not related to pathologic grading and tubulointerstitial injury (P > 0.05). CONCLUSION: The serum albumin and IgG levels of the NP group were significantly lower; however, their blood urea nitrogen and cystatin C levels were higher. The ISKDC grades were mainly above grade III. The prognosis of the NP group was associated with clinical classification and improved after a timely and early treatment.

[Clinical Significance of Serum Midkine in Children with Henoch-Schonlein Purpura].

OBJECTIVE: To investigate the clinical significance of serum midkine (MK) in children with henoch-schnlein purpura(HSP). METHODS: One hundred and six children with HSP admitted in our hospital from March 2013 to March 2016 were enrolled in HSP group, but then 80 healthy volunteers were used as control. MK, interleukin-2 (IL-2), IL-4, IL-6, IL-10, tumor necrosis factor (TNF), interferon γ (IFN-γ) and IL-17 in peripheral blood were measured by ELISA, biochemical indicators including white blood cell count (WBC), platelet (Plt), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), D-dimer, immunoglobulin A (IgA), IgE, IgG, IgM and other clinical data were recorded and analyzed. RESULTS: Among 106 cases of henoch-schonlein purpura, 42 patients combined with renal failure (isolated hematuria in 4 cases, 17 cases of isolated proteinuria, hematuria and proteinuria in 21 cases). Midkine level in children with HSP was significantly higher than that in the control group [291.70(248.50-396.41) pg/ml vs 217.30(198.98-243.65) pg/ml)](P<0.05); the MK level in group of HSP with nephritis was higher than that in group of HSP without nephritis [326.58(266.58-459.25) pg/ml vs 280.72(233.67-384.36) pg/ml] (P<0.05). IL-4, IL-6, IL-17, TNF and IFN-γ levels in children with HSP were higher than those in the control group(P<0.05), but IL-10 level was lower than that in control group. IL-2 level was not significantly different between 2 groups. Cytokines levels in HSP nephritis group and HSP without renal involvement were not significantly different. Pearson correlation analysis showed that midkine level positively correlated with IL-4, IL-6, IL-17, IgA and IgE (P<0.05). By ROC curve analysis, the AUC of midkine was 0.902, 95% CI 0.841-0.963 (P<0.001), threshold 295.50 pg/ml. The sensitivity and specificity of midkine for predicting Henoch-Schonlein purpura nephritis were 80.60% and 88.30% respecitvely. CONCLUSION: Plasma MK plays an important role in the development of Henoch-Schonlein purpura and Henoch-Schonlein purpura nephritis. Plasma MK can be used as an effective indicator for early diagnosis and prediction of HSP and renal damage.

Histopathological and immunological changes during the acute and recovery phase in Henoch-Schönlein purpura rabbit model.

Henoch-Schönlein purpura (HSP) is a systemic vasculitis mediated by autologous immune complex. Animal models of HSP are scarce. Here, we describe the characteristics of HSP rabbit model in the acute and recovery phase. First, we constructed the HSP rabbit models, and then assessed immunologic indicators of models by enzyme-linked immunosorbent assay and immunoturbidimetry. Histomorphological characteristics were analyzed by haematoxylin-eosin, immunofluorescence and special staining. In the acute stage (24 h) after antigen challenge, the model group rabbits featured skin ecchymosis and abnormal laboratory examination results. Three weeks following the allergic reaction, purple spots improved markedly, and edema and blood seeping decreased, but obvious inflammation was present in the skin, kidneys, joints, gastrointestinal, lung and liver. Serological results of CD4, CD/CD8, IL-2, IL-4, and TNF-α, IgA, IgG, TropI, Alb and T were still abnormal. IgA and C3 expressed in skin and kidney and eosinophils expressed in skin and lungs were increased. The rabbit model can mimic human HSP lesions in symptoms, pathology, and immunology and may provide valuable insight into the pathogenesis of HSP and serve as a tool for future therapeutic development targeting HSP.

Differences in pathological characteristics and laboratory indicators in adult and pediatric patients with Henoch-Schönlein purpura nephritis.

We aimed to investigate the differences in renal histopathological changes and laboratory parameters between adult and pediatric patients with Henoch-Schönlein purpura nephritis (HSPN), and to analyze the correlation between laboratory parameters and renal histopathological grading. A total of 139 patients diagnosed with HSPN between September 2010 and December 2014 at the First Hospital of Jilin University, China, were retrospectively reviewed. The clinical and pathological characteristics were examined and compared between the adult and the pediatric patients. A majority of adult (75.0%) and pediatric (66.2%) patients were categorized as pathological grade III HSPN. Adults having crescent lesions, interstitial fibrosis and renal artery involvement significantly outnumbered child counterparts (all P<0.05). Pathological grading showed a positive correlation with 24-h urine protein (r=0.307, P=0.009), microalbuminuria (r=0.266, P=0.000) and serum globulin (r=0.307, P=0.014), and a negative correlation with serum albumin (r=0.249, P=0.037) in pediatric patients with HSPN. Among adult patients with HSPN, histopathological grading showed a positive correlation with 24-h urine protein (r=0.294, P=0.015), microalbuminuria (r=0.352, P=0.006), α1-microglobulin (r=0.311, P=0.019) and immunoglobulin G (r=0.301, P=0.023) in urine, and serum creatinine (r=0.292, P=0.018). Further, a negative correlation between serum albumin and pathological grading was also observed (r=0.291, P=0.018). In conclusion, the severity of renal pathological lesions in HSPN patients is well reflected by the levels of proteinuria. Adult patients have more severe renal histopathological changes than pediatric patients.

The significance of tubulointerstitial lesions in childhood Henoch-Schönlein nephritis.

BACKGROUND: Little information is currently available on the development of tubulointerstitial lesions in children with Henoch-Schönlein nephritis (HSN). To identify the impact of the development of tubulointerstitial changes in HSN, we retrospectively analyzed renal biopsies obtained from children with HSN. METHODS: Twenty-eight children with HSN from whom serial renal biopsies had been obtained before and after immunosuppressive therapy were enrolled in the study. The patients were divided into two groups according to the observed change in tubulointerstitial lesion development: group I (n = 15), with stable or improved tubulointerstitial lesions, and group II (n = 13), with worsened tubulointerstitial lesions. Group II patients had longer duration of proteinuria than group I patients (3.7 ± 3.7 years vs. 1.7 ± 1.7 years, p = 0.052). RESULTS: The change in serum albumin level was negatively correlated with the change in tubulointerstitial scores before and after treatment (γ = -0.444, p = 0.018). Group II patients showed a significant decrease in immunoglobulin G (IgG) and IgA deposits after treatment (p = 0.039 and 0.003, respectively), while group II patients did not (p = 0.458 and 0.506, respectively). CONCLUSIONS: Although the International Study of Kidney Disease in Children classification of HSN does not include tubulointerstitial lesions, they can progress during treatment and could have significant clinical implications in association with the duration of proteinuria.