A survey of plasma IgA, IgG, IgM in pediatric patients with primary nephritic syndrome

Journal of military pharmaco-medicine n o 1-2020 159 A SURVEY OF PLASMA IgA, IgG, IgM IN PEDIATRIC PATIENTS WITH PRIMARY NEPHRITIC SYNDROME Nguyen Thi Thu Hien1; Pham Van Tran2; Le Viet Thang2 SUMMARY Objectives: To survey plasma IgA, IgG and IgM concentrations and their association with some features in pediatric patients with primary nephritic syndrome. Subjects and methods: A cross-sectional study was performed on 94 subjects, including 61 children with primary nephrotic syndrome and 33 healthy controls. All subjects were assessed for plasma IgA, IgG and IgM levels by means of turbidity immunoassay. Results: The median levels of plasma IgA, IgG, IgM were 1.08; 2.23; 1.84 g/L. The rate of patients decreased IgA, IgG, IgM level compared with the control group was 3.3; 88.5 and 0%. IgG concentrations were closely correlated, IgM was inversely correlated with serum albumin, p < 0.01. IgG levels were inversely related to proteinuria 24 h, p < 0.01. Conclusion: Decreased IgG level was common in patients with primary nephritic syndrome.. * Keywords: Primary nephrotic syndrome; Serum IgA, IgG, IgM concentration; Children. INTRODUCTION Nephritic syndrome (NS) is a syndrome that includes clinical and biochemical symptoms that occur in both adults and children. The nephritic syndrome is characterized by edema (many patients have serious cavity effusion), much proteinuria and selection with urinary albumin accounts for > 80%, reduced blood protein and blood albumin and dyslipidemia. Renal syndrome often appears suddenly, unexplained, is essentially the process of glomerular membrane damage, causing protein to be released much of urine. The process of glomerular membrane damage takes place in a special nature, causing the protein to escape, mainly albumin to the urine. Other disorders of NS are manifestations of albumin drainage. In children, NS is often primary, involving changes in the levels of immunoglobulin including IgA, IgG and IgM and genetic factors. Changing levels of immune immunoglobulin are associated with high urinary protein excretion and deposition of these immunoglobulin in the glomerulus [5, 6]. Determination of these immunoglobulin levels in patients with primary nephritic syndrome is necessary for clinicians. From the above reasons, we carried out the topic: - To study plasma concentrations of IgA, IgG, IgM in children with NS. - To find the relationship between IgA, IgG, IgM and serum albumin, proteinuria 24 hours in primary NS in children. 1. Phu Tho Medical College 2. 103 Military Hospital Corresponding author: Nguyen Thi Thu Hien (bshienpt@gmail.com) Date received: 18/12/2019 Date accepted: 15/01/2020 Journal of military pharmaco-medicine n o 1-2020 160 SUBJECTS AND METHODS 1. Subjects. Subjects of study included 94 children, divided into 2 groups: - Disease group: Including 61 children with primary nephritic syndrome diagnosed and treated in the Department of Nephrology and Urology, Central Pediatric Hospital. - Control group: 33 healthy children. * Inclusion criteria: - Pediatric patients aged 06 months and older were diagnosed with primary NS according to the criteria of Japanese and International Nephrology Association on childhood kidney disease: Proteinuria ≥ 50 mg/kg/24 hours, blood albumin ≤ 25 g/L, blood protein ≤ 56 g/L. - Being allowed by parents to participate in the study * Exclusion criteria: - Congenital NS: detectable NS < 3 months after birth. - Patients with acute diseases such as fever virus, pneumonia, bronchitis... - The patient was suspected of having a surgical disease. 2. Methods. - Study design: Cross-sectional descriptions, case-control studies. - Investigating medical history: Pregnancy history, previous renal diseases and other illness. - Physical examination: Laboratory. - Tests: Complete blood count (CBC), biochemical blood test. - Collecting 24 hour urine for proteinuria quantification. - In pediatric patients, NS is mostly caused by minimal lesions, only a small percentage of the patients had glomerulo- nephritis. - Measurement of IgA, IgG and IgM levels: Briefly, a venous blood sample was taken (from each subject) into an anticoagulant coated tube and then plasma was separated into another test tube. Ig levels in plasma were measured by turbidimetric immunoassay. A value of an Ig level was considered normal if it is within a quartile of the control values. Elevated values of Ig level are defined as those greater than upper limit of the controls an decreased values as those below the lower limit of a quartile of the controls. - Data is processed by SPSS 22.0 software. The graph is automatically drawn on the computer. Journal of military pharmaco-medicine n o 1-2020 161 RESULTS AND DISCUSSION 1. Characteristics of the children and concentrations of IgA, IgG, IgM in children with primary NS. Table 1: Comparison of age, gender between the study group and control one. Study group (n = 61) Control group (n = 33) Characteristics n Ratio % n Ratio % Average ages 6.32 ± 3.36 7.12 ± 2.66 p > 0.05 < 5 30 49.2 8 24.2 5 - <10 23 37.7 19 57.6 Age group 10 - < 16 8 13.1 6 18.2 Male 41 67.2 20 60.6 Sex Female 20 32.8 13 39.4 The average age of the group of patients in our study was 6 years, which was not different from the control group (control group was 7 years old). The proportion of female patients in the study was 32.8%, male accounted for 67.2%. There was no difference between the male and female proportions of the study group and the control group. Our results were in line with those reported in other studies: Nguyen Thi Yen et al (2012), Pham Van Dem et al (2016), El Mashad G.M et al (2017)) [2, 3, 7]. However, the study results showed that the age of our NS patients was lower than that of Youssef D.M et al (2011) [8]. Table 2: Characteristics of protein concentration, blood albumin and proteinuria (n = 61). Characteristics Patients Ratio (%) Reduction rate < 56 g/L 44 72.1 Protein (g/L) Average level 49.88 ± 12.08 Reduction rate < 25 g/L 48 78.7 Albumin (g/L) Average level 24.73 ± 10.7 Median (quartet) 8.79 (5.31 - 17.58) 24-hour proteinuria (g) Min - max 3.59 - 46.1 Characteristics of blood albumin, protein and 24-hour proteinuria showed very low average protein and albumin concentrations, whereas the average proteinuria was very high. Our findings were similar to those reported by other authors. In adults as well Journal of military pharmaco-medicine n o 1-2020 162 as children, the mechanism of urinary protein excretion is related to three processes: glomerular membrane damage, membrane charge disorders and hemodynamic disorders in glomerular vascular coils. In pediatric patients, NS is mostly caused by minimal lesions, only a small percentage has glomerulonephritis. With minimal trauma, major structural changes are epithelial swelling (the podocytes) and the leg system of these cells. This lesion leads to glomerular membrane structure that loses stability, resulting in a wide filter hole and causing protein extravasation, high proteinuria, mainly albumin [9, 10]. In this study, 24-hour proteinuria in the children patient was the highest (46.1 grams). Table 3: Comparison of IgA, IgG and IgM levels in the study and control group. Index Control group (n = 33) Study group (n = 61) p Median 1.09 (0.89 - 1.44) 1.08 (0.85 - 1.38) Min 0.52 0.26 IgA (g/L) Max 2.92 2.86 > 0.05 Median 10.61 (9.79 - 12.82) 2.23 (1.11 - 5.33) Min 8.52 0.48 IgG (g/L) Max 18.5 11.09 < 0.001 Median 1.29 (1.15 - 2.02) 1.84 (1.38 - 2.23) Min 0.57 0.59 IgM (g/L) Max 4.07 3.44 < 0.01 Comparing the levels of immunoglobulin, we found that there was no similar change in these immunoglobulins. The average concentration of IgA in plasma in children was lower than that in healthy children, but there was no significant difference. By contrast, the average plasma IgG concentration was lower, IgM was higher than the control group with statistical significance with p < 0.05. Table 4: Percentage of patients with increased, decreased IgA, IgG, IgM compared to the control group. Index Number of patients Ratio % Increase 0 0.0 IgA (g/L) Decrease 2 3.3 Increase 0 0.0 IgG (g/L) Decrease 54 88.5 Increase 0 0.0 IgM (g/L) Decrease 0 0.0 (Limitation of Igs’s levels: IgA: 0.52 - 2.91g/L; IgG: 8.52 - 18.49 g/L; IgM: 0.57 - 4.03 g/L). Journal of military pharmaco-medicine n o 1-2020 163 The proportion of patients with reduced IgA levels was 3.3%, IgG decreased by 88.5% and IgM decreased by 0% compared to the control group. When compared with the results by the authors in the country, we had not recorded a notice, but compared to the study by foreign authors, we found similarities. The study by Youssef D.M et al (2011) [8] on 2 groups: 27 pediatric patients including 16 patients with corticosteroids resistance of average age of 12.3 years, 11 patients with sensitivity to corticosteroids, the average age of 11.6 years, compared to 20 healthy children the average age was 12.1 years. The results showed that plasma concentrations of IgA, IgG and IgM were 2.4; 11.8 and 1.5 g/L while concentration in our study was 1.25; 11.57 and 1.55 g/L. In the group of diseases, IgA and IgG levels were also lower, IgM levels were also higher. For this reason, we believed that reducing the concentration of IgA and IgG in pediatric patients was reasonable because the amount of IgA, IgG was eliminated through the urinary tract and deposited in the glomerular so the blood’s Ig concentration decreased. In contrary, with large dimension IgM, as well as very little IgM deposited in the glomerulus, the concentration may increase slightly. 2. Relation between of IgA, IgG, IgM levels and albumin, proteinuria 24 hours in children with primary NS. Table 5: Correlated concentrations of Igs with blood albumin levels. Albumin (g/L) Index of correlation assessment r p Correlation equation IgA (g/L) 0.214 > 0.05 - IgG (g/L) 0.794 < 0.001 IgG = 0.228*albumin - 2.029 IgM (g/L) -0.35 < 0.01 IgM = 2.38 - 0.02*albumin There was a favourable correlation and contrary correlated with a low level between plasma IgG concentration, IgM and serum albumin, p < 0.01. IgG = 0.228*albumin - 2.029 0 2 4 6 8 10 12 0 10 20 30 40 50 Albumin (g/L) Ig G (g/ L) Chart 1: Correlation of IgG concentration with blood albumin concentration (n = 61). IgG concentrations were positively correlated with close levels of serum albumin, r = 0.794, p < 0.001. Journal of military pharmaco-medicine n o 1-2020 164 IgM = 2.38 - 0.02*albumin 0 1 2 3 4 0 10 20 30 40 50 Albumin (g/L) Ig M (g/ L) Chart 2: Correlation of IgM concentration with albumin concentration (n = 61). IgM concentrations had a low inverse correlation with blood albumin, r = -0.35, p < 0.01. Table 6: Correlation of concentrations of Igs with 24-hour proteinuria (n = 61). 24-hour proteinuria (g) Index of correlation assessment r p Correlation equation IgA (g/L) -0.24 > 0.05 - IgG (g/L) -0.432 < 0.01 IgG = 5.231 - 0.122*proteinuria 24h IgM (g/L) 0.119 > 0.05 - There was a negative correlation between low levels of plasma IgA and IgG levels with 24-hour proteinuria in pediatric patients with NS, p < 0.01. IgG = 5.231 - 0,122*proteinuria 24h 0 2 4 6 8 10 12 0 10 20 30 40 50 Proteinuria 24h (g) Ig G (g/ L) Chart 3: Correlation of IgG concentration with 24h proteinuria (n = 61). IgG concentrations had a low inverse correlation with 24-hour proteinuria, r = -0.432, p < 0.01. Journal of military pharmaco-medicine n o 1-2020 165 On finding the correlation concentration of IgA, IgG and IgM with blood albumin concentration and 24-hour proteinuria, we found a correlation between the concentration of immunoglobulin IgG and IgM with these quantities. Explaining this correlation, we believe that it is related to the mechanism of protein loss in urine and the synthesis of albumin from the liver. Thus, the concentration of immunoglobulin is closely related to the process of proteinuria in patients with primary NS. CONCLUSION Survey of plasma concentrations of IgA, IgG and IgM of 61 patients with primary NS, compared with 33 healthy children, we draw some comments: - The average concentration of IgA, IgG, IgM in the group of patients was 1.08 2.23; 1.84 g/L, respectively. The proportion of pediatric patients reduced the concentration of IgA, IgG, IgM compared to the control group was 3.3; 88.5 and 0%. - IgG concentration had a positive correlation with close level, IgM was inversely correlated with low level of blood albumin concentration, p < 0.01. Concentrations of IgG had a low inverse correlation with 24-hour proteinuria, p < 0.01. REFERENCES 1. Vũ Thị Thơm, Nguyễn Quỳnh Hương, Phạm Văn Đếm và CS. 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