Proteins of TNF-α and IL6 Pathways Are Elevated in Serum of Type-1 Diabetes Patients with Microalbuminuria
Soluble cytokine receptors may play an important role in development of microalbuminuria (MA) in type-1 diabetes (T1D). In this study, we measured 12 soluble receptors and ligands from TNF-α/IL6/IL2 pathways in T1D patients with MA (n = 89) and T1D patients without MA (n = 483) participating in the...
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| Format: | Article |
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Frontiers Media S.A.
2018-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2018.00154/full |
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| author | Sharad Purohit Sharad Purohit Sharad Purohit Ashok Sharma Wenbo Zhi Shan Bai Diane Hopkins Leigh Steed Bruce Bode Stephen W. Anderson John Chip Reed R. Dennis Steed Jin-Xiong She Jin-Xiong She |
| author_facet | Sharad Purohit Sharad Purohit Sharad Purohit Ashok Sharma Wenbo Zhi Shan Bai Diane Hopkins Leigh Steed Bruce Bode Stephen W. Anderson John Chip Reed R. Dennis Steed Jin-Xiong She Jin-Xiong She |
| author_sort | Sharad Purohit |
| collection | DOAJ |
| description | Soluble cytokine receptors may play an important role in development of microalbuminuria (MA) in type-1 diabetes (T1D). In this study, we measured 12 soluble receptors and ligands from TNF-α/IL6/IL2 pathways in T1D patients with MA (n = 89) and T1D patients without MA (n = 483) participating in the PAGODA study. Twelve proteins in the sera from T1D patients with and without MA were measured using multiplex Luminex assays. Ten serum proteins (sTNFR1, sTNFR2, sIL2Rα, MMP2, sgp130, sVCAM1, sIL6R, SAA, CRP, and sICAM1) were significantly elevated in T1D patients with MA. After adjusting for age, duration of diabetes, and sex in logistic regression, association remained significant for seven proteins. MA is associated with increasing concentrations of all 10 proteins, with the strongest associations observed for sTNFR1 (OR = 108.3, P < 10−32) and sTNFR2 (OR = 65.5, P < 10−37), followed by sIL2Rα (OR = 12.9, P < 10−13), MMP2 (OR = 5.5, P < 10−6), sgp130 (OR = 5.2, P < 10−3), sIL6R (OR = 4.6, P < 10−4), and sVCAM1 (OR = 3.3, P < 10−4). We developed a risk score system based on the combined odds ratios associated with each quintile for each protein. The risk scores cluster MA patients into three subsets, each associated with distinct risk for MA attributable to proteins in the TNF-α/IL6 pathway (mean OR = 1, 13.5, and 126.3 for the three subsets, respectively). Our results suggest that the TNF-α/IL6 pathway is overactive in approximately 40% of the MA patients and moderately elevated in the middle 40% of the MA patients. Our results suggest the existence of distinct subsets of MA patients identifiable by their serum protein profiles. |
| first_indexed | 2024-04-12T02:38:54Z |
| format | Article |
| id | doaj.art-82fc48a28f0b41d788ad20a79bd9d95d |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-12T02:38:54Z |
| publishDate | 2018-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-82fc48a28f0b41d788ad20a79bd9d95d2022-12-22T03:51:23ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-01-01910.3389/fimmu.2018.00154314526Proteins of TNF-α and IL6 Pathways Are Elevated in Serum of Type-1 Diabetes Patients with MicroalbuminuriaSharad Purohit0Sharad Purohit1Sharad Purohit2Ashok Sharma3Wenbo Zhi4Shan Bai5Diane Hopkins6Leigh Steed7Bruce Bode8Stephen W. Anderson9John Chip Reed10R. Dennis Steed11Jin-Xiong She12Jin-Xiong She13Center for Biotechnology and Genomic Medicine, Augusta University, Augusta, GA, United StatesDepartment of Obstetrics and Gynecology, Medical College of Georgia, Augusta University, Augusta, GA, United StatesDepartment of Medical Laboratory, Imaging, and Radiologic Sciences, College of Allied Health Sciences, Augusta University, Augusta, GA, United StatesCenter for Biotechnology and Genomic Medicine, Augusta University, Augusta, GA, United StatesCenter for Biotechnology and Genomic Medicine, Augusta University, Augusta, GA, United StatesCenter for Biotechnology and Genomic Medicine, Augusta University, Augusta, GA, United StatesCenter for Biotechnology and Genomic Medicine, Augusta University, Augusta, GA, United StatesCenter for Biotechnology and Genomic Medicine, Augusta University, Augusta, GA, United StatesAtlanta Diabetes Associates, Atlanta, GA, United StatesPediatric Endocrine Associates, Atlanta, GA, United StatesSoutheastern Endocrine & Diabetes, Atlanta, GA, United StatesSoutheastern Endocrine & Diabetes, Atlanta, GA, United StatesCenter for Biotechnology and Genomic Medicine, Augusta University, Augusta, GA, United StatesDepartment of Obstetrics and Gynecology, Medical College of Georgia, Augusta University, Augusta, GA, United StatesSoluble cytokine receptors may play an important role in development of microalbuminuria (MA) in type-1 diabetes (T1D). In this study, we measured 12 soluble receptors and ligands from TNF-α/IL6/IL2 pathways in T1D patients with MA (n = 89) and T1D patients without MA (n = 483) participating in the PAGODA study. Twelve proteins in the sera from T1D patients with and without MA were measured using multiplex Luminex assays. Ten serum proteins (sTNFR1, sTNFR2, sIL2Rα, MMP2, sgp130, sVCAM1, sIL6R, SAA, CRP, and sICAM1) were significantly elevated in T1D patients with MA. After adjusting for age, duration of diabetes, and sex in logistic regression, association remained significant for seven proteins. MA is associated with increasing concentrations of all 10 proteins, with the strongest associations observed for sTNFR1 (OR = 108.3, P < 10−32) and sTNFR2 (OR = 65.5, P < 10−37), followed by sIL2Rα (OR = 12.9, P < 10−13), MMP2 (OR = 5.5, P < 10−6), sgp130 (OR = 5.2, P < 10−3), sIL6R (OR = 4.6, P < 10−4), and sVCAM1 (OR = 3.3, P < 10−4). We developed a risk score system based on the combined odds ratios associated with each quintile for each protein. The risk scores cluster MA patients into three subsets, each associated with distinct risk for MA attributable to proteins in the TNF-α/IL6 pathway (mean OR = 1, 13.5, and 126.3 for the three subsets, respectively). Our results suggest that the TNF-α/IL6 pathway is overactive in approximately 40% of the MA patients and moderately elevated in the middle 40% of the MA patients. Our results suggest the existence of distinct subsets of MA patients identifiable by their serum protein profiles.http://journal.frontiersin.org/article/10.3389/fimmu.2018.00154/fullinflammationcytokinescytokine receptorsdiabetesmicroalbuminuria |
| spellingShingle | Sharad Purohit Sharad Purohit Sharad Purohit Ashok Sharma Wenbo Zhi Shan Bai Diane Hopkins Leigh Steed Bruce Bode Stephen W. Anderson John Chip Reed R. Dennis Steed Jin-Xiong She Jin-Xiong She Proteins of TNF-α and IL6 Pathways Are Elevated in Serum of Type-1 Diabetes Patients with Microalbuminuria Frontiers in Immunology inflammation cytokines cytokine receptors diabetes microalbuminuria |
| title | Proteins of TNF-α and IL6 Pathways Are Elevated in Serum of Type-1 Diabetes Patients with Microalbuminuria |
| title_full | Proteins of TNF-α and IL6 Pathways Are Elevated in Serum of Type-1 Diabetes Patients with Microalbuminuria |
| title_fullStr | Proteins of TNF-α and IL6 Pathways Are Elevated in Serum of Type-1 Diabetes Patients with Microalbuminuria |
| title_full_unstemmed | Proteins of TNF-α and IL6 Pathways Are Elevated in Serum of Type-1 Diabetes Patients with Microalbuminuria |
| title_short | Proteins of TNF-α and IL6 Pathways Are Elevated in Serum of Type-1 Diabetes Patients with Microalbuminuria |
| title_sort | proteins of tnf α and il6 pathways are elevated in serum of type 1 diabetes patients with microalbuminuria |
| topic | inflammation cytokines cytokine receptors diabetes microalbuminuria |
| url | http://journal.frontiersin.org/article/10.3389/fimmu.2018.00154/full |
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