Important denominator between autoimmune comorbidities: a review of class II HLA, autoimmune disease, and the gut

Berryman, Meghan A.; Ilonen, Jorma; Triplett, Eric W.; Ludvigsson, Johnny

doi:10.3389/fimmu.2023.1270488

Cited by 7 publications

(5 citation statements)

References 143 publications

(237 reference statements)

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“…The primary function of HLA-DR is to present peptide antigens, potentially foreign in origin, to the immune system for the purpose of eliciting or suppressing T-helper responses that eventually lead to the production of antibodies against the same peptide antigen [56]. In the instance of an infection, the peptide is bound into a DR molecule and presented to a few T-cell receptors found on T-helper cells.…”

Section: Resultsmentioning

confidence: 99%

Immunological Profile and Markers of Endothelial Dysfunction in Elderly Patients with Cognitive Impairments

Goncharov,

Popova,

Kudryavtsev

et al. 2024

IJMS

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The process of aging is accompanied by a dynamic restructuring of the immune response, a phenomenon known as immunosenescence. Further, damage to the endothelium can be both a cause and a consequence of many diseases, especially in elderly people. The purpose of this study was to carry out immunological and biochemical profiling of elderly people with acute ischemic stroke (AIS), chronic cerebral circulation insufficiency (CCCI), prediabetes or newly diagnosed type II diabetes mellitus (DM), and subcortical ischemic vascular dementia (SIVD). Socio-demographic, lifestyle, and cognitive data were obtained. Biochemical, hematological, and immunological analyses were carried out, and extracellular vesicles (EVs) with endothelial CD markers were assessed. The greatest number of significant deviations from conditionally healthy donors (HDs) of the same age were registered in the SIVD group, a total of 20, of which 12 were specific and six were non-specific but with maximal differences (as compared to the other three groups) from the HDs group. The non-specific deviations were for the MOCA (Montreal Cognitive Impairment Scale), the MMSE (Mini Mental State Examination) and life satisfaction self-assessment scores, a decrease of albumin levels, and ADAMTS13 (a Disintegrin and Metalloproteinase with a Thrombospondin Type 1 motif, member 13) activity, and an increase of the VWF (von Willebrand factor) level. Considering the significant changes in immunological parameters (mostly Th17-like cells) and endothelial CD markers (CD144 and CD34), vascular repair was impaired to the greatest extent in the DM group. The AIS patients showed 12 significant deviations from the HD controls, including three specific to this group. These were high NEFAs (non-esterified fatty acids) and CD31 and CD147 markers of EVs. The lowest number of deviations were registered in the CCCI group, nine in total. There were significant changes from the HD controls with no specifics to this group, and just one non-specific with a maximal difference from the control parameters, which was α1-AGP (alpha 1 acid glycoprotein, orosomucoid). Besides the DM patients, impairments of vascular repair were also registered in the CCCI and AIS patients, with a complete absence of such in patients with dementia (SIVD group). On the other hand, microvascular damage seemed to be maximal in the latter group, considering the biochemical indicators VWF and ADAMTS13. In the DM patients, a maximum immune response was registered, mainly with Th17-like cells. In the CCCI group, the reaction was not as pronounced compared to other groups of patients, which may indicate the initial stages and/or compensatory nature of organic changes (remodeling). At the same time, immunological and biochemical deviations in SIVD patients indicated a persistent remodeling in microvessels, chronic inflammation, and a significant decrease in the anabolic function of the liver and other tissues. The data obtained support two interrelated assumptions. Taking into account the primary biochemical factors that trigger the pathological processes associated with vascular pathology and related diseases, the first assumption is that purine degradation in skeletal muscle may be a major factor in the production of uric acid, followed by its production by non-muscle cells, the main of which are endothelial cells. Another assumption is that therapeutic factors that increase the levels of endothelial progenitor cells may have a therapeutic effect in reducing the risk of cerebrovascular disease and related neurodegenerative diseases.

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Section: Resultsmentioning

confidence: 99%

Immunological Profile and Markers of Endothelial Dysfunction in Elderly Patients with Cognitive Impairments

Goncharov,

Popova,

Kudryavtsev

et al. 2024

IJMS

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“…However we can not rule out the interplay between genetic predisposition and enviromental factors as well the participation of other genes outside the HLA region [ 33 , 34 ]. Recently the participation of the dysbiosis in this pathogenic process has been pointed out [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

Prevalence of autoimmune diseases in an admixed population of patients with type 1 diabetes: a multicenter study in Brazil

Gomes,

Braga,

Drummond

et al. 2024

Diabetol Metab Syndr

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Background/objectives The primary aim of this study was to evaluate the prevalence of autoimmune diseases (AIDs) and its associated factors in an admixed Brazilian population of patients with type 1 diabetes (T1D). The secondary one was to determine the relationship between AIDs and the occurrence of diabetes-related chronic complications (DRCC). Methods This cross-sectional, nationwide survey was conducted in 13 public clinics in 11 Brazilian cities. Overall, 1,760 patients were included; 967 females (55.9%), 932 (54%) Caucasians, aged 29.9 ± 11.9 years, age at diagnosis 14.8 ± 8.9 years, diabetes duration 15.5 ± 9.3 years and 12.2 ± 3.8 years of school attendance. AIDs were retrieved from medical records or self-report and stratified as follows: absence of AIDs, only autoimmune thyroid disease (AITD), and other AIDs including the combination with AITD (hyper or hypothyroidism). Results The prevalence of AIDs was 19.5% being AITDs (16.1%), the most frequently found. A higher prevalence of hypertension, dyslipidemia and overweight or obesity was found in patients who had exclusively AITDs. A higher prevalence of diabetic retinopathy (DR) was observed in patients with AITDs and patients with other AIDs in combination with AITDs. Chronic kidney disease (CKD) was more prevalent in patients with only AITDs. Lower levels of HbA1C, were observed in patients with isolated AITDs or with other AIDs, regardless of the presence of AITD. Hierarchical multivariate analysis, showed that AIDs were associated with female gender, older age, and longer diabetes duration, self-reported color-race (White and Brown), geographic region (Brazilian North/Northeast region) and higher anti-TPO levels (≥ 35 UI/ml). Conclusions In conclusion, Brazilian patients with T1D, belonging to a highly ethnically admixed population, had an important prevalence of AIDs, mostly AITDs, that was associated with female gender, self-reported color-race, older age and longer diabetes duration. Moreover, these patients also had a higher prevalence of DRCC. Even though we highlight the importance of investigating the presence of AIDs at diagnosis and at regular intervals, it is unclear whether screening and early detection of additional AIDs may improve the clinical outcomes in individuals with T1D. Future prospective studies are necessary to establish the interplay between T1D, AIDs and DRCC.

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“…Analyses in children with a double diagnosis also demonstrated a strong positive correlation between GAL-1 and composite estimates of several cytokines, with the strongest positive correlation found when combining IL-1β, IL-6, and TNF-α, but also a positive correlation to Th1-associated IFN-γ and the T1D-associated immune marker visfatin. T1D and CeD share several common risk factors, including common risk-associated human leukocyte antigen (HLA)-haplotypes, and microbiotic alterations in the gut [ 49 ]. However, there are both common and unique risk factors for T1D and CeD, and it may be that children with a double diagnose present certain HLA-haplotypes and lack of gut microbiota diversity to a larger degree than those with only one diagnosis.…”

Section: Discussionmentioning

confidence: 99%

Galectin-1 correlates with inflammatory markers and T regulatory cells in children with type 1 diabetes and/or celiac disease

Fryk,

Wilsson,

Tompa

et al. 2023

Clinical and Experimental Immunology

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Type 1 diabetes (T1D) and celiac disease (CeD) are common autoimmune diseases in children where the pathophysiology is not fully characterized. The autoimmune process involves a complex scenario of both inflammatory and regulatory features. Galectin-1 (GAL-1) has a wide range of biological activities e.g., interaction with immune cells. We examined the relationship between GAL-1 and soluble immune markers and T cell subsets in a cohort of children with T1D and/or CeD relative to healthy children. Galectin-1, together with several soluble immune markers (e g interleukins (IL)), tumor necrosis factor (TNF), acute phase proteins and matrix metalloproteinases (MMP) were measured in sera from children with T1D and/or CeD by fluorochrome (Luminex) technique using children without these diseases as a reference. Subgroups of T cells, including T regulatory (Treg) cells, were analyzed by flow cytometry. Association between GAL-1, pro-inflammatory markers and Treg cells differed depending on which illness combination was present. In children with both T1D and CeD, GAL-1 correlated positively with pro-inflammatory markers (IL-1β, -6 and TNF-α). Composite scores increased the strength of correlation between GAL-1 and pro-inflammatory markers, Th1-associated interferon (IFN)-γ, and T1D-associated visfatin. Contrary, in children diagnosed with exclusively T1D, GAL-1 was positively correlated to CD25hi and CD25hiCD101+ Treg cells. For children with only CeD, no association between GAL-1 and other immune markers was observed. In conclusion, the association observed between GAL-1, soluble immune markers and Treg cells may indicate a role for GAL-1 in the pathophysiology of T1D and, to some extent, also in CeD.

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Important denominator between autoimmune comorbidities: a review of class II HLA, autoimmune disease, and the gut

Cited by 7 publications

References 143 publications

Immunological Profile and Markers of Endothelial Dysfunction in Elderly Patients with Cognitive Impairments

Immunological Profile and Markers of Endothelial Dysfunction in Elderly Patients with Cognitive Impairments

Prevalence of autoimmune diseases in an admixed population of patients with type 1 diabetes: a multicenter study in Brazil

Galectin-1 correlates with inflammatory markers and T regulatory cells in children with type 1 diabetes and/or celiac disease

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