Effects of dexamethasone and gamma globulin combined with prednisone on the therapeutic effect and immune function of Henoch‐Schonlein purpura nephritis in children

Abstract Background Henoch‐Schonlein purpura nephritis (HSPN) is a serious complication of Henoch‐Schonlein purpura (HSP), which is usually treated with immunosuppressant and glucocorticoid. This study was designed to explore the effect of dexamethasone and gamma globulin combined with prednisone in the treatment of pediatric HSPN. Methods According to the treatment plan, 60 children treated with dexamethasone and gamma globulin were included in the control group, and the rest 55 children treated with dexamethasone and gamma globulin combined with prednisone were selected as the research group. The clinical manifestations, therapeutic effect, immune function, serum inflammatory factors, blood coagulation function, urine routine, renal function, and adverse reactions were compared between the two groups. Results The clinical manifestations of children in the research group were significantly better than those in the control group after treatment (P < .05). The total effective rate in the research group (94.55%) was markedly higher than that in the control group (76.67%) (P < .05). CD3+, CD4+, CD8+, IL‐10, PT, and APTT increased while CD4+/CD8+, IgA, IL‐8, TNF‐α, FIB, urine protein, urine red blood cell, Scr, and BUN decreased in both groups after treatment, and the changes of all the above indexes in the research group were significant than those in the control group (P < .05). The incidence of adverse reactions in the research group was remarkably superior to that in the control group (P < .05). Conclusion Dexamethasone and gamma globulin combined with prednisone can improve the immune function of children with HSPN and promote the recovery of renal function.


| INTRODUC TI ON
Henoch-Schonlein purpura (HSP) in children is a systemic inflammatory vascular disease with infection as the main inducement. In the initial stage, children with HSP often show extrarenal symptoms like skin purpura, joint pain, and hemorrhagic gastroenteritis and, in some cases, manifest as asymptomatic urine abnormalities. Generally, as the disease progresses, there will be renal injury of varying severity, glomerular damage, and interference with the reabsorption function of trace albumin. 1,2 While as a serious complication of HSP, Henoch-Schonlein purpura nephritis (HSPN) is a kind of systemic disease with impaired renal parenchyma, which is more prevalent in children. 3,4 In most cases, it can be diagnosed by the occurrence of hematuria or proteinuria in the course of disease within 6 months in clinic. 5 The pathological manifestations often change from necrotizing vasculitis to renal injury of varying degrees, persistent renal damage that eventually involves the whole body, and even renal failure. 6 Today, the pathogenesis of HSPN has not been accurately determined, but it has been clinically confirmed to be related to the disorder of cellular and humoral immunity. 7 Currently, immunosuppressive agents and glucocorticoid therapy for HSPN are widely used in clinical practice, but the treatment effect is still affected by factors such as poor tolerance and adverse reactions in children, leading to recurrence after drug withdrawal. 8 Studies have shown 9 that dexamethasone has a long-lasting inhibitory effect on monocyte-macrophages phagocytosis and destruction of antibody-attached platelets, which can improve capillary permeability and peripheral blood circulation, and ensure the smooth hematopoiesis of bone marrow. While gamma globulin can prevent the formation of vicious circle of platelet damage by blocking Fc receptor reduction in mononuclear phagocytic system and reducing the production of autoantibody. 10 However, at present, the combination therapy with the above two drugs cannot reach the satisfactory treatment effect in HSPN. As a new generation of anabolic steroids, prednisone has better anti-inflammatory and anti-immune biological efficacy than other glucocorticoids, but its application in HSPN still lacks relevant research. Therefore, this paper compared and analyzed the therapeutic effect of dexamethasone and gamma globulin combined with prednisone on children with HSPN, in order to find a better treatment for HSPN.

| General information
A total of 115 children with HSPN hospitalized in Cangzhou Central Hospital from July 2016 to August 2018 were selected as the research participants. Based on the treatment plan, 60 children treated with dexamethasone and gamma globulin were included in the control group, and the rest 55 children treated with dexamethasone and gamma globulin combined with prednisone were selected as the research group. Among them, there were 65 boys and 50 girls, and 24 cases of grade I, 54 cases of grade II, and 37 cases of grade III when classified by renal pathological grading, with an average age of 6.49 ± 1.42 years. There was no significant difference in age, gender, and other general information between the two groups (P > .05), suggesting comparability.

| Inclusion and exclusion criteria
Inclusion criteria are as follows: Children who met the clinical diagnostic criteria of HSPN. 11

| Outcome measures
(a) Clinical indicators such as the average renal involvement time, urinary protein excretion, and serum β2-microglobulin were recorded by peripheral blood test and urine test. (b) The treatment efficacy was evaluated. According to clinical symptoms (complete disappearance, disappearance, improvement, no improvement, or exacerbation), 24 hours proteinuria, and urinary red blood cells (negative, decrease by more than 50%, decrease by more than 25%, no change), the treatment efficacy was divided into cured, improved, effective, and ineffective. Total clinical effective rate = (cured + improved + effective)/total number of cases × 100%. 12

| Statistical methods
Statistical analysis was performed using statistical software SPSS 21.0 (ND Times Technology Co., Ltd., Beijing, China). The counting data were compared by chi-square test, while the measurement data were expressed as mean ± standard deviation, and intra-or intergroup comparisons were performed by t test. P < .05 indicated a statistically significant difference.

| Comparison of clinical manifestations between two groups of children with HSPN after treatment
After treatment, the average renal involvement time of (4.03 ± 0.67) weeks, urinary protein excretion of (347.35 ± 132.43) mg/d, and serum β2 microglobulin of (0.23 ± 0.07) mg/L) in the research group were dramatically better than those in the control group (P < .05). (Table 1).

| Comparison of therapeutic effects between the two groups of children treated by different treatment methods
The total effective rate in the research group was markedly higher than that in the control group (P < .05). (Table 2).

| Comparison of immune function between the two groups before and after treatment
There were no significant differences in the immune function indexes of CD3+, CD4+, CD8+, CD4+/CD8+, and IgA between the two groups before treatment. After treatment, the levels of CD3+, CD4+, CD8+ increased, while CD4+/CD8+ and IgA decreased in the two groups, and the extent of change in the research group was more obvious than that in the control group (P < .05). (Figure 1).

| Changes of serum inflammatory factors in the two groups before and after treatment
No marked differences were noticed in serum inflammatory factors levels represented by IL-8, IL-10, and TNF-α between the two groups before treatment (P > .05). After treatment, the levels of IL-8 and TNF-α in the two groups decreased, while IL-10 level increased, and the change in the research group was more significant than that in the control group (P < .05). (Figure 2).

| Changes of coagulation function in the two groups before and after treatment
Before treatment, there were no significant differences in coagulation function indexes between the two groups (P > .05). After treatment, FIB decreased while PT and APTT increased in the two groups, with a larger change extent in the research group (P < .05).

| Comparison of urine routine indexes between the two groups before and after treatment
The urine protein and urine red blood cell routine indexes did not identify any marked difference between the two groups before treatment (P > .05). While after treatment, the urine protein and urine red blood cell routine indexes dropped in both groups, and the change in the research group was more significant than that in the control group (P < .05). (Figure 4).

| Comparison of renal function indexes between the two groups before and after treatment
The renal function indexes of Scr and BUN did not differ significantly between the two groups before treatment, but the Scr and BUN in both groups decreased after treatment, and the change in the research group was more obvious than that in the control group (P < .05). (Figure 5).

| Comparison of adverse reactions between the two groups
The incidence of adverse reactions in the research group (9.09%) was remarkably lower than that in the control group (23.33%) (P < .05).

F I G U R E 1
Comparison of immune function indexes between the two groups before and after treatment. A, After treatment, the CD3 + level of children in both groups increased, and its change in the research group was more obvious than that in the control group. B, After treatment, the CD4 + level of children in both groups elevated, and its change in the research group was more significant than that in the control group. C, After treatment, the CD8 + level of children in both groups increased, and its change in the research group was more significant than that in the control group. D, After treatment, the ratio of CD4+/CD8+ decreased in both groups, and the change in the research group was more significant than that in the control group. E, After treatment, the IgA level of the two groups of children declined, and the IgA level in the research group changed more significantly than that in the control group. Note: * represents the comparison between the two groups, P < .05 gastrointestinal, and joint symptoms) for renal function impairment in HSP. As all the above factors can be analyzed from the aspects of inflammatory response and immunity, in this study, the combination of prednisone and the control drugs, dexamethasone, and gamma globulin were compared to observe the indicators influencing the improvement of prognosis in the two groups of children.
In vitro, the recovery degree of HSNP was compared mainly by objective phenomena such as urinary protein excretion and renal involvement time. The observation results showed that the research group was superior to the control group in clinical performance and treatment efficacy. In order to further explore the causes of different therapeutic effects, we specifically studied the changes in children's body during the treatment. It was found that there were no significant differences in inflammatory or immune indexes between the two groups of children before treatment, while the inflammatory and immune indexes were improved in both groups after treatment, and the extent of change in the research group was better than that in the control group.

In HSPN patients, the interaction between CD40 of T cells and interleukin cells produced by Th2 cells can stimulate the acti-
vation, synthesis of autoantibodies, and mass proliferation of B cells. 21 Dexamethasone can control the rate of platelet rise in the body and reduce the peak time of platelets, thus affecting the phagocytosis of immune cells in the body. 22 As to gamma globulin, it contains broad-spectrum IgG antibodies against bacteria or pathogens, and its immunoglobulin has a unique complex antibody immune network, which can produce certain anti-infection and immunomodulatory effects. Its injection can improve the level of specific antibodies such as IgG in the body, inhibit Th2 from activating Th1, restore the balance between the two, and ease the allergic reaction of the body. 23,24 While by reducing the possibility F I G U R E 2 Comparison of the changes of serum inflammatory factors between the two groups before and after treatment. A, After treatment, the IL-8 level of children in both groups decreased, and the change of IL-8 level in the research group was more significant than that in the control group. B, After treatment, the IL-10 level of children in both groups increased, and the change of IL-10 level in the research group was more significant than that in the control group. C, After treatment, the TNF-α level of children in both groups reduced, and the change of TNF-α level in the research group was more significant than that in the control group. Note: * represents the comparison between the two groups, P < .05

F I G U R E 3
Changes of coagulation function in the two groups before and after treatment. A, After treatment, the PT increased in both groups, and the increase in the research group was more significant than that in the control group. B, After treatment, the FIB reduced in both groups, and the decrease in the research group was more significant than that in the control group. C, After treatment, the APTT elevated in both groups, and the increase in the research group was more significant than that in the control group. Note: * represents the comparison between the two groups, P < .05 of hyperemia, prednisone prevents inflammatory cells from moving toward the inflammatory site, controls the response of inflammatory mediators and phagocytosis, and regulates the stability of lysosomal membrane and Th factors. 25 All these suggest that The results showed that the coagulation function of children in both groups improved after treatment, while that of the children F I G U R E 4 Comparison of urine routine indexes between the two groups before and after treatment. A, After treatment, the urine protein in both groups decreased within 24 h, and the change in the research group was more obvious than that in the control group. B, The urine red blood cells reduced in the two groups after treatment, and the decrease in the research group was more obvious than that in the control group. Note: * represents the comparison between the two groups, P < .05 F I G U R E 5 Comparison of renal function indexes between the two groups before and after treatment. A, After treatment, the Scr level decreased in the two groups, and the decrease in the research group was more obvious than that in the control group. B, After treatment, the BUN level reduced in both groups, and the decrease in the research group was more obvious than that in the control group. Note: * represents the comparison between the two groups, P < .05