Clinical characteristics and autoantibody pattern in newly diagnosed adult‑onset autoimmune diabetes

Paschke, Anna; Grzelka, Agata; Zawada, Agnieszka; Zozulińska‐Ziółkiewicz, Dorota

doi:10.20452/pamw.1831

Cited by 7 publications

(8 citation statements)

References 8 publications

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“…21,33,34 The rs4251719*A -rs2306630*A--rs2107538*A CCL5 haplotype associated with low RANTES production protects from type 1 diabetes, an autoimmune disorder which shares several genetic and pathophysiologic features with AAD. 21,35 To summarize, this study demonstrates for the first time elevated serum RANTES levels in patients with AAD and confirms previous reports about the functional role of the rs2107538 CCL5 variant, which may alter circulating RANTES levels. Further studies, especially in asymptomatic individuals at high risk of AAD, such as adrenal autoantibody -positive first--degree relatives, are warranted to evaluate if this chemokine might be a useful biomarker or even a therapeutic target at early stages of autoimmune adrenal insufficiency.…”

Section: Methodssupporting

confidence: 89%

Elevated serum RANTES chemokine in autoimmune Addison’s disease

Fichna¹,

Żurawek²,

Budny³

et al. 2018

Polish Archives of Internal Medicine

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INTRODUCTION Regulated on activation, normal T‑cell expressed and secreted chemokine (RANTES), the product of the CCL5 gene, is involved in trafficking immune cells into the inflammation site. It acts as coactivator of T cells and promotes polarization of the immune response towards the Th1 profile. In autoimmune Addison disease (AAD), the adrenal cortex is gradually destroyed by adrenal‑specific immune cell infiltration. RANTES might be implicated in autoimmune adrenal failure through recruitment and activation of the immune cells. Furthermore, the promoter CCL5 variant, rs2107538, seems to be associated with autoimmune endocrine conditions: diabetes and thyroid disease. OBJECTIVES Our analysis was designed to evaluate the prevalence of rs2107538 and serum RANTES levels in AAD. PATIENTS AND METHODS rs2107538 was genotyped using TaqMan technology in 239 individuals with AAD and 542 controls, while serum RANTES levels were evaluated by an enzyme‑linked immunosorbent assay in 114 patients with AAD and 111 healthy age- and sex‑matched individuals. RESULTS No differences were found in rs2107538 genotype or allele frequencies between patients and controls (P = 0.53 and P = 0.39, respectively), and no association was detected with age at AAD onset (P = 0.14). Serum RANTES levels were elevated in patients with AAD compared with controls (mean [SD], 59.2 [30.3] ng/ml vs 45.5 [20.4] ng/ml, P = 0.001). Healthy carriers of various rs2107538 genotypes demonstrated differences in serum RANTES levels (P = 0.02), whereas AAD patients did not (P = 0.26). No correlation was found between circulating RANTES levels and age, AAD duration, serum autoantibodies, hydrocortisone dose, and body mass (P >0.05). CONCLUSIONS This study demonstrates for the first time elevated serum RANTES levels in AAD and confirms that rs2107538 may affect serum chemokine levels.

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Section: Methodssupporting

confidence: 89%

Elevated serum RANTES chemokine in autoimmune Addison’s disease

Fichna¹,

Żurawek²,

Budny³

et al. 2018

Polish Archives of Internal Medicine

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“…47 In addition, the higher prevalence of multiple autoantibodies in younger patients may be a possible cause for disease onset earlier in life. 48 A recent study, however, showed no differences in age at diagnosis, duration of diabetes, or ethnic distribution was observed between GADA-negative and positive patients. 49 Both BMI and WC of our LADA patients were significantly lower than Type 2 DM, which is in agreement with those reported for European and Asian populations.…”

mentioning

confidence: 90%

Latent Autoimmune Diabetes in Adults (LADA) and its Metabolic Characteristics among Yemeni Type 2 Diabetes Mellitus Patients

Al-Zubairi¹,

AL-Habori²,

Saif-Ali³

2021

DMSO

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Purpose: Although there is ample data about the prevalence of diabetes in the Middle East, little is known about the prevalence and features of autoimmune diabetes in this region. The aim of this study was to investigate the prevalence and metabolic characteristics of latent autoimmune diabetes in adults (LADA) amongst Yemeni Type 2 DM patients. Patients and Methods: In this cross-section study, 270 Type 2 DM patients aged 30-70 years were recruited from the National Diabetes Center, Al-Thowra Hospital, Sana'a city, during the period November 2015 to August 2016. All Type 2 DM patients were diagnosed within 5 years and who did not require insulin for a minimum of 6 months following diagnosis. Levels of glutamic acid decarboxylase autoantibodies (GADA) were measured in all patients, and LADA was diagnosed in patients testing positive for anti-GAD antibodies. Further, biochemical analysis was carried out including fasting blood glucose (FBG), glycated haemoglobin (HbA1c), insulin, and lipid profile. Insulin resistance (HOMA-IR) and β-cell function (HOMA-β) were calculated. Results:The prevalence of LADA, as defined by GADA-positive, amongst patient with Type 2 DM was 4.4%; with no significant difference in the prevalence between male (5.8%) and female (3.4%). LADA patients were younger than GADA-negative Type 2 DM. Body mass index, waist circumference, insulin and HOMA-β were significantly lower in LADA patients, whereas triglyceride, cholesterol, HDL-c and HOMA-IR were non-significantly lower with respect to Type 2 DM. In contrast, FBG and HbA1c were significantly higher in LADA patients. Moreover, the prevalence of metabolic syndrome was significantly lower in LADA as compared with Type 2 DM. Only 2 out of the 12 GADA-positive (16.7%) were on insulin treatment at the time of the study. Conclusion:The prevalence of LADA in Yemeni Type 2 DM is lower than many of those reported in the literature, with no gender preference. Metabolic syndrome was significantly lower in LADA patients. Patients with LADA share insulin resistance with Type 2 DM but display a more severe defect in β-cell function, thus highlighting the importance of an early diagnosis of LADA, to correctly treat LADA patients, allowing safe and effective therapies.

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“…[35–38]. We can take evidence from published literature or clinical observations of autoimmunity linked with above mentioned disease pathogenesis and look whether the underlining cause of autoimmunity lies within gut bacterial peptides.…”

Section: Discussionmentioning

confidence: 99%

Gut bacterial peptides with autoimmunity potential as environmental trigger for late onset complex diseases: In–silico study

2017

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Recent evidences suggest that human gut microbiota with major component as bacteria can induce immunity. It is also known that gut lining depletes with ageing and that there is increased risk of autoimmune and inflammatory disorders with ageing. It is therefore likely that both may be correlated as depletion of gut lining exposes the gut bacterial antigens to host immune mechanisms, which may induce immunity to certain bacterial proteins, but at the same time such immunity may also be auto-immunogenic to host. This autoimmunity may make a protein molecule nonfunctional and thereby may be involved in late onset metabolic, autoimmune and inflammatory disorders such as, Diabetes, Rheumatoid Arthritis, Hyperlipidemias and Cancer. In this in-silico study we found a large number of peptides identical between human and gut bacteria which were binding to HLA-II alleles, and hence, likely to be auto-immunogenic. Further we observed that such autoimmune candidates were enriched in bacterial species belonging to Firmicutes and Proteobacteria phyla, which lead us to conclude that these phyla may have higher disease impact in genetically predisposed individuals. Functional annotation of human proteins homologous to candidate gut-bacterial peptides showed significant enrichment in metabolic processes and pathways. Cognitive trait, Ageing, Alzheimer, Type 2 diabetes, Chronic Kidney Failure (CKF), Chronic Obstructive Pulmonary Disease (COPD) and various Cancers were the major diseases represented in the dataset. This dataset provides us with gut bacterial autoimmune candidates which can be studied for their clinical significance in late onset diseases.

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Clinical characteristics and autoantibody pattern in newly diagnosed adult‑onset autoimmune diabetes

Cited by 7 publications

References 8 publications

Elevated serum RANTES chemokine in autoimmune Addison’s disease

Elevated serum RANTES chemokine in autoimmune Addison’s disease

Latent Autoimmune Diabetes in Adults (LADA) and its Metabolic Characteristics among Yemeni Type 2 Diabetes Mellitus Patients

Gut bacterial peptides with autoimmunity potential as environmental trigger for late onset complex diseases: In–silico study

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