Urine Proteomic Analysis of Differences Between Patients With Hyperthyroidism Before and After Carbimazole Treatment

Abstract Background: Hyperthyroidism, characterised by increased circulating thyroid hormone (TH) levels, alters the body’s metabolic and systemic haemodynamic balance and directly influences renal function However, the underlying mechanisms and metabolic implications of these changes are not well understood. Objective: In the present study we aimed to study the changes occurring in the urinary proteome of patients with hyperthyroidism before and after treatment. The levels of the excreted proteins in the urine were studied using an untargeted 2D DIGE MALDI TOF proteomic approach with network analysis. Methods: The study included 9 age matched patients with mean age 38.6 ± 12.1 years with newly diagnosed hyperthyroidism. The patients were evaluated at baseline and after receiving treatment with carbimazole. Urine samples were obtained from the same patient at baseline (hyperthyroid state) with serum FT4 levels of 35.4 + 9.9 pmol/L and TSH 0.014 + 0.014 mIU/L (mean + SD), and post treatment with anti-thyroid drugs (euthyroid state) with levels of FT4 17.0 + 2.8 pmol/L and TSH 0.6 + 0.5 mIU/L (mean + SD). Results: Alterations in the abundance of urinary proteins, analyzed by Progenesis software, revealed statistically significant differential abundance in a total of 40 spots corresponding to 33 proteins, 26 up and 7 down (≥1.5-fold change, ANOVA, p ≤ 0.05). The proteins identified in the study are known to regulate processes related to cellular metabolism, transport, acute phase response. The urinary proteins upregulated with hyperthyroidism included serotransferrin, transthyretin, serum albumin, ceruloplasmin, α1B glycoprotein, syntenin-1, nesprin, and glutamilnyl peptide cyclotransferase while the 3 notable down regulated proteins were plasma kallikrein, protein glutamine gamma-glutamyl transferase and serpin B3. Bioinformatic analysis using Ingenuity Pathway Analysis (IPA) identified dysregulation of pathways related to cellular compromise, inflammatory response, cellular assembly and organization and identified the involvement of the APP and AKT signaling pathways via their interactions with interleukins as the central nodes. Conclusion: The urine proteomic profiling between the hyperthyroid and euthyroid states demonstrates alteration in the protein levels involved in acute phase response and in maintaining an individual’s haemodynamic state.

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Proteomics Profiling of the Urine of Patients with Hyperthyroidism after Anti-Thyroid Treatment

Molecules ◽

10.3390/molecules26071991 ◽

2021 ◽

Vol 26 (7) ◽

pp. 1991

Author(s):

Hicham Benabdelkamel ◽

Afshan Masood ◽

Aishah A. Ekhzaimy ◽

Assim A. Alfadda

Keyword(s):

Bioinformatic Analysis ◽

Gamma Glutamyl Transferase ◽

Urinary Proteins ◽

Systemic Hemodynamic ◽

2D Dige ◽

Proteomic Approach ◽

Significant Difference ◽

Before And After ◽

Thyroid Hormone Levels ◽

Glutamyl Transferase

Hyperthyroidism, which is characterized by increased circulating thyroid hormone levels, alters the body’s metabolic and systemic hemodynamic balance and directly influences renal function. In this study, the urinary proteome of patients with hyperthyroidism was characterized using an untargeted proteomic approach with network analysis. Urine samples were collected from nine age-matched patients before and after carbimazole treatment. Differences in the abundance of urinary proteins between hyperthyroid and euthyroid states were determined using a 2D-DIGE coupled to MALDI-TOF mass spectrometry. Alterations in the abundance of urinary proteins, analyzed via Progenesis software, revealed a statistically significant difference in abundance in a total of 40 spots corresponding to 32 proteins, 25 up and 7 down (≥1.5-fold change, ANOVA, p ≤ 0.05). The proteins identified in the study are known to regulate processes associated with cellular metabolism, transport, and acute phase response. The notable upregulated urinary proteins were serotransferrin, transthyretin, serum albumin, ceruloplasmin, alpha-1B-glycoprotein, syntenin-1, and glutaminyl peptide cyclotransferase, whereas the three notable downregulated proteins were plasma kallikrein, protein glutamine gamma-glutamyl transferase, and serpin B3 (SERPINB3). Bioinformatic analysis using ingenuity pathway analysis (IPA) identified the dysregulation of pathways associated with cellular compromise, inflammatory response, cellular assembly, and organization and identified the involvement of the APP and AKT signaling pathways via their interactions with interleukins as the central nodes.

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Proteomic approach to identify acute phase response-related proteins with low molecular weight in loach skin following injury

PROTEOMICS ◽

10.1002/pmic.200300864 ◽

2004 ◽

Vol 4 (12) ◽

pp. 3989-3997 ◽

Cited By ~ 19

Author(s):

Xuanxian Peng ◽

Yajun Wu ◽

Jingan Chen ◽

Sanying Wang

Keyword(s):

Molecular Weight ◽

Acute Phase ◽

Acute Phase Response ◽

Phase Response ◽

Low Molecular Weight ◽

Proteomic Approach ◽

Related Proteins

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Characteristics Associated with Acute-Phase Response following First Zoledronic Acid Infusion in Brazilian Population with Osteoporosis

Journal of Osteoporosis ◽

10.1155/2021/9492883 ◽

2021 ◽

Vol 2021 ◽

pp. 1-7

Author(s):

Bruno S. A. Ferreira ◽

Bernardo M. da Cunha ◽

Luciana P. Valadares ◽

Larissa A. Moreira ◽

Frederico G. A. Batista ◽

...

Keyword(s):

Zoledronic Acid ◽

Acute Phase ◽

Acute Phase Response ◽

Laboratory Data ◽

Phase Response ◽

Symptom Duration ◽

Acid Infusion ◽

Hydroxyvitamin D ◽

Oral Bisphosphonate ◽

Before And After

We aimed to evaluate characteristics associated with acute-phase response (APR) following first zoledronic acid infusion in a Brazilian cohort. This retrospective cohort study enrolled all adults with osteoporosis who underwent a first zoledronic acid infusion at our centre between June 2015 and June 2019. Clinical demographics (age, sex, diabetes, smoking, body mass index, and previous oral bisphosphonate use) and laboratory data (calcium, parathyroid hormone, renal function, and serum 25-hydroxyvitamin D and carboxy-terminal crosslinked telopeptide of type 1 collagen [CTX], both before and after infusion) were compared between patients with and without APR. We evaluated association magnitude between the presence of APR and clinical variables through logistic regression. This study enrolled 400 patients (women, 80%). APR was observed in 24.5% (n = 98) of patients. The mean symptom duration in days was 3.5 ± 2.8. Patients with APR were younger (67 ± 12 vs. 71 ± 11 years; p = 0.001 ), used oral bisphosphonates less frequently (34% × 50%; p = 0.005 ), and had greater baseline CTX (0.535 ng/mL [0.375, 0.697] × 0.430 [0.249, 0.681]; p = 0.03 ) and ΔCTX (−69 [−76; −50] × −54 [−72; −23]; p = 0.002 ) than those without APR. The other variables were similar between the groups. Only ΔCTX was associated (OR, 0.62; 95% CI 0.41–0.98) with APR after accounting for age and bisphosphonate use. APR occurred in 24.5% of the cohort. Younger age and absence of prior oral bisphosphonate use were associated with APR following first zoledronic acid infusion. APR was associated with ΔCTX (but no other variables) after adjusting for these factors.

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