Hubungan Kadar Vitamin D (25(OH)D) Terhadap Sel T Helper 17, T Regulator, Rasio T Helper 17 Terhadap T Regulator, dan Skor SLEDAI Anak dengan Lupus Eritematosus Sistemik

Monica, Charity and Dr. dr. Harjoedi Adji Tjahjono,, Sp.A(K) and Dr. dr. Wisnu Barlianto,, Sp.A(K), MSi.Med (2023) Hubungan Kadar Vitamin D (25(OH)D) Terhadap Sel T Helper 17, T Regulator, Rasio T Helper 17 Terhadap T Regulator, dan Skor SLEDAI Anak dengan Lupus Eritematosus Sistemik. Magister thesis, Universitas Brawijaya.

Abstract

Dua tabung ungu dikirim ke laboratorium medik Fakultas Kedokteran Universitas Brawijaya Malang untuk diperiksakan persentase T helper 17 dan T regulator. Satu tabung kuning diperiksakan di laboratorium sentral RSUD Dr. Saiful Anwar Malang untuk diperiksakan kadar vitamin D (25(OH)D) serta kadar ANA serta anti-dsDNA pasien. Analisis dilakukan dengan membandingkan pasien dengan kadar vitamin D yang cukup dibandingkan dengan pasien dengan kadar vitamin D yang kurang (insufisiensi atau defisiensi). Uji analisis komparatif dilakukan dengan uji Chisquare untuk data nominal, dan uji T-test tidak berpasangan atau Mann-Whitney bila data berdistribusi tidak normal untuk data numerik. Uji korelasi antara kadar vitamin D dengan sel T helper 17, T regulator, rasio T helper 17 terhadap T regulator, dan skor SLEDAI menggunakan uji korelasi Spearman. Uji analisis dianggap signifikan bila nilai p0,05. Analisis dilakukan dengan software SPSS statistic 25 for windows. Usia rata-rata subjek adalah 13.463.28 tahun. Mayoritas subjek berjenis kelamin perempuan, yaitu sebanyak 30 subjek adalah perempuan dan hanya 2 subjek laki-laki. Rerata kadar vitamin D 20.2910.22 ng/mL dengan mayoritas pasien memiliki kadar vitamin D yang abnormal, yaitu 25 dari 32 pasien (78.12%). Hanya 8 pasien memiliki kadar vitamin D yang cukup. Rerata persentase sel T helper 17 adalah 12.5413.26, persentase sel T regulator adalah 9.177.35, dan rerata rasio sel T helper 17 terhadap T regulator adalah 1.731.72. Rerata skor SLEDAI adalah 13.885.46. Mayoritas pasien, yaitu 27 pasien termasuk ke dalam kategori derajat aktivitas penyakit sedang-berat (skor 7) dan sebanyak 5 pasien termasuk ke dalam kategori derajat aktivitas penyakit ringan (skor 6). Tidak terdapat perbedaan signifikan pada rerata persentase T helper 17 pada kelompok vitamin D abnormal (insufisiensi dan defisiensi) dibanding kelompok vitamin D yang cukup, yaitu sebesar 12.9914.39 dibanding 11.189.81 (uji Mann-Whitney p= 0.881). Uji korelasi Spearman menunjukkan tidak terdapat hubungan antara kadar vitamin D dengan persentase T helper 17 (r= 0.069, p= 0.708). Terdapat perbedaan signifikan pada persentase T regulator pada kelompok vitamin D abnormal dibanding kelompok vitamin D yang cukup, yaitu 7.566.59 vs 147.81 (uji Mann-Whitney p= 0.018). Uji korelasi Spearman menunjukkan terdapat hubungan antara kadar vitamin D dengan persentase T regulator dengan kekuatan yang lemah (r= 0.402, p= 0.023). Terdapat perbedaan signifikan pada rasio T helper 17 terhadap T regulator pada kelompok vitamin D abnormal dibanding kelompok vitamin D yang cukup, yaitu 2.041.87 vs 0.80.52 (uji Mann-Whitney p= 0.029). Uji korelasi Spearman menunjukkan terdapat hubungan negatif yang lemah antara kadar vitamin D dengan rasio T helper 17 terhadap T regulator (r= -0.441, p= 0.012). Kemudian, uji chi-square derajat aktivitas penyakit (SLEDAI) berdasarkan status vitamin D menunjukkan perbedaan yang signifikan antar dua kelompok (p= 0.029). Uji korelasi Spearman menunjukkan terdapat hubungan berbanding terbalik yang signifikan dan sangat kuat antara kadar vitamin D dengan skor SLEDAI (r= -0.958 dan p= 0.000). Uji path analysis menunjukkan bahwa tidak terdapat hubungan yang signifikan antara x kadar vitamin D dengan skor SLEDAI melalui baik persentase T helper 17, T regulator, maupun rasio T helper 17 terhadap T regulator. Berdasarkan hasil tersebut, dapat disimpulkan bahwa terdapat hubungan yang signifikan antara kadar vitamin D dengan sel T regulator, rasio T helper 17 terhadap T regulator, dan skor SLEDAI pasien anak dengan lupus eritematosus sistemik.

English Abstract

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease in children with clinical symptoms involving various organ systems. This disease progresses with more severe disease activity, higher morbidity and mortality in children than in adults. The incidence of childhood-onset SLE ranges from 0.36 to 2.5 per 100,000 children per year. The etiology of SLE is said to be multifactorial, including genetic risk factors, epigenetic mechanisms, and environmental triggers. Systemic lupus erythematosus is characterized by the production of antibodies that attack the body itself, namely anti-nuclear antibodies (ANA), anti-phospholipid antibodies, anti-Smith, and anti-ribonucleoprotein. These autoantibodies then cause overproduction of proinflammatory cytokines and cause dysregulation of the innate and adaptive immune systems. Various T cell dysfunctions occur in SLE patients, such as abnormalities in the selection or activation of T cells, premature aging of T cells, and an imbalance in the ratio of T helper 17 to regulatory T cells. An increase in the ratio of T helper 17 cells compared to regulatory T cells is said to play a role in increasing the degree of activity of several autoimmune diseases, one of which is SLE through the SLEDAI (Systemic Lupus Erythematosus Disease Activity Index 2000) score. Children with SLE are susceptible to vitamin D deficiency due to various things such as photosensitive nature, renal complications, and the treatment of SLE itself. Research conducted by Terrier B et al.'s in SLE patients with vitamin D deficiency shows that vitamin D supplementation stimulates an increase in naïve CD4+ T cells and regulatory T cells, and conversely decreases effector T helper 1 and T helper 17 cells. Several studies show that vitamin D deficiency or lower vitamin D levels is associated with a higher degree of disease activity or SLEDAI score. This study aims to determine the relationship between vitamin D (25(OH)D) levels and T helper 17 cells, T regulators, the ratio of T helper 17 to T regulators, and the SLEDAI score of children with systemic lupus erythematosus. This study was a cross-sectional study on 32 pediatric patients with systemic lupus erythematosus in the outpatient and inpatient pediatric clinics at RSUD Dr. Saiful Anwar Malang from January to May 2022. Subjects were pediatric patients aged 6-18 years and diagnosed with systemic lupus erythematosus based on the 2012 SLICC criteria. Blood samples were taken in 3 tubes for each patient, namely 2 purple tubes containing 2 cc of blood each and 1 yellow tube containing 3 cc of xii blood. The two purple tubes were sent to the medical laboratory of the Faculty of Medicine, Brawijaya University Malang to check the percentage of T helper 17 and T regulator. The yellow tube was examined at the central laboratory of RSUD Dr. Saiful Anwar Malang to have the patient's vitamin D (25(OH)D) levels and ANA and anti-dsDNA levels checked. The analysis was carried out by comparing patients with sufficient vitamin D levels compared to patients with insufficient vitamin D levels (insufficiency or deficiency). Comparative analysis tests were carried out using the Chi-square test for nominal data, and the unpaired T-test or Mann-Whitney test was used if the numerical data was not normally distributed. Correlation Test between vitamin D levels and T helper 17 cells, T regulators, the ratio of T helper 17 to T regulators, and SLEDAI scores was conducted using the Spearman correlation test. The analysis test is considered significant if the p value is 0.05. The analysis was carried out using SPSS statistics 25 for windows software. The average age of the subjects was 13.463.28 years. The majority of the subjects were female, 30 subjects were female and only 2 subjects were male. The mean vitamin D level was 20.2910.22 ng/mL with the majority of patients having abnormal vitamin D levels, namely 25 of 32 patients (78.12%). Only 8 patients had adequate vitamin D levels. The average percentage of T helper 17 cells was 12.5413.26, the percentage of T regulatory cells was 9.177.35, and the average ratio of T helper 17 cells to T regulators was 1.731.72. The mean SLEDAI score was 13.885.46. The majority of patients, namely 27 patients, fell into the moderate-severe disease activity category (score 7) and 5 patients fell into the mild disease activity category (score 6). The Mann-Whitney comparison test showed that there was no significant difference in the percentage of T helper 17 based on vitamin D levels (p= 0.881), with mean percentage of T helper 17 in the abnormal (insufficiency or deficiency) vs normal vitamin D group was 12.9914.39 compared to 11.189.81. The Spearman correlation test showed that there was no relationship between vitamin D levels and the percentage of T helper 17 (r= 0.069, p= 0.708). The Mann-Whitney comparison test showed that there was a significant difference in the percentage of T regulator based on vitamin D levels, with mean percentage of regulatory T cells in the sufficient vitamin D group was higher 147.81 compared to 7.566.59 in the abnormal group (p value = 0.018). The Spearman correlation test showed that there was a weak relationship between vitamin D levels and the percentage of T regulators (r= 0.402, p= 0.023). The Mann-Whitney comparison test showed that there was a significant difference in the ratio of T helper 17 to T regulator based on vitamin D levels, with mean ratio of T helper 17 to T regulator in the abnormal vitamin D group was higher 2.041.87 compared to 0.80.52 in the sufficient group (p= 0.029). The Spearman correlation test showed that there was a weak negative relationship between vitamin D levels and the ratio of T helper 17 to T regulator (r= -0.441, p= 0.012). Then, the Chi-Square comparison test of disease activity (SLEDAI) based on vitamin D status showed a significant difference within two groups (p= 0.029). The Spearman correlation test showed that there was a significant and very strong inverse relationship between vitamin D levels and xiii SLEDAI scores (r= -0.958 and p= 0.000). The path analysis test showed that there was no significant relationship between vitamin D levels and SLEDAI scores through either the percentage of T helper 17, T regulator, or the ratio of T helper 17 to T regulator. Based on these results, it can be concluded that there is a significant relationship between vitamin D levels and regulatory T cells, the ratio of T helper 17 to T regulator, and the SLEDAI score of pediatric patients with systemic lupus erythematosus.

Item Type: Thesis (Magister)
Identification Number: 042306
Uncontrolled Keywords: Kadar vitamin D, T helper 17, T regulator, rasio T helper 17 terhadap T regulator, Vitamin D levels, T helper 17, T regulators, ratio of T helper 17 to T regulator
Divisions: Profesi Kedokteran > Spesialis Ilmu Kesehatan Anak, Fakultas Kedokteran
Depositing User: Unnamed user with username ihwan
Date Deposited: 10 Jan 2024 08:38
Last Modified: 10 Jan 2024 08:38
URI: http://repository.ub.ac.id/id/eprint/207641
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