Immunoglobulin M gene association with autoantibody reactivity and type 1 diabetes

Rolim, Inês; Duarte, Nádia; Barata, Gabriela; Costa, João; Gardete-Correia, L.; Boavida, José Manuel; Duarte, Rui A; Raposo, João Filipe; Peerally, Zulmira; Catarino, Manuela; Penha‐Gonçalves, Carlos

doi:10.1007/s00251-017-0999-1

Cited by 6 publications

(4 citation statements)

References 38 publications

(39 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…2; Table S2). This region, included within the immunoglobulin heavy chain (IGH) cluster (Lefranc et al 2009;Massari et al 2009;Matiasovic et al 2009;Bao et al 2010;Mineccia et al 2012;Hwang et al 2018;Martin et al 2018), harbours the immunoglobulin heavy constant mu (IGHM) gene, previously associated with autoantibody reactivity and T1D (Rolim et al 2017), and 36 novel ENSEMBL genes, predicted based on cDNA sequence information from dog, with 29 of them containing immunoglobulin-like domains (Table S2).…”

Section: Resultsmentioning

confidence: 99%

“…Recently, Rolim et al (2017) performed a human casecontrol study and a family-based cohort comprising a total of 240 T1D patients, 172 first-degree relatives and 130 unrelated healthy controls, and they proved that variants at the IGH cluster are genetic determinants of autoantibodies against pancreatic antigens and contribute to T1D susceptibility. Our results are in line with these findings and further support the idea that control of autoantibody generation by polymorphisms in the IGH cluster may be a component of the genetic susceptibility to DM not only in humans, but also in dogs.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Polymorphisms in canine immunoglobulin heavy chain gene cluster: a double‐edged sword for diabetes mellitus in the dog

et al. 2021

View full text Add to dashboard Cite

Insulin deficiency diabetes (IDD) in dogs is an endocrine disease similar to human type 1 diabetes. There are breeds more commonly affected, such as Yorkshire Terrier and Samoyed, suggesting an underlying genetic component. However, the genetic basis for canine diabetes mellitus (DM) is not fully established. We conducted both whole-genome scans for selection signatures and GWASs to compare the genomes of 136 dogs belonging to 29 breeds previously described at low or high risk for developing DM. Candidate variants were tested in dogs with a diagnosis of IDD and controls attending the Complutense Veterinary Teaching Hospital. The only genomic region under selection (CFA8:72 700 000-74 600 000; CanFam3.1) retrieved by our analyses is included in the immunoglobulin heavy chain gene cluster, which has already been related to human human type 1 diabetes susceptibility. This region contains two non-synonymous variants, rs852072969 and rs851728071, showing significant associations with high or low risk for IDD, respectively. The first variant, rs852072969, alters a protein poorly characterised in the dog. In contrast, rs851728071 was predicted to block the synthesis of an immunoglobulin variable (V) domain in breeds at low risk for DM. Although a large and diverse V gene repertoire is thought to offer a fitness advantage, we suggest that rs851728071 prevents the formation of an auto-reactive immunoglobulin V domain probably involved in the pathophysiology of IDD and, thus, decreases the risk for the disease. These results should be interpreted with caution until the functional roles of the proposed variants have been proved in larger studies.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Polymorphisms in canine immunoglobulin heavy chain gene cluster: a double‐edged sword for diabetes mellitus in the dog

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Nevertheless, reduced total plasma IgM has recently been reported in school aged children with type 1 diabetes 28 . Certain variants of the IGHM gene locus have been associated with an increased risk to type 1 diabetes 29 , 30 . Interestingly, in a plasma proteomic study of twins, both IGHM and its binding partner CD5L were reported among the top proteins, that were mostly affected by heritability 20 .…”

Section: Discussionmentioning

confidence: 99%

Serum APOC1 levels are decreased in young autoantibody positive children who rapidly progress to type 1 diabetes

Hirvonen,

Lietzén,

Moulder

et al. 2023

Sci Rep

View full text Add to dashboard Cite

Better understanding of the early events in the development of type 1 diabetes is needed to improve prediction and monitoring of the disease progression during the substantially heterogeneous presymptomatic period of the beta cell damaging process. To address this concern, we used mass spectrometry-based proteomics to analyse longitudinal pre-onset plasma sample series from children positive for multiple islet autoantibodies who had rapidly progressed to type 1 diabetes before 4 years of age (n = 10) and compared these with similar measurements from matched children who were either positive for a single autoantibody (n = 10) or autoantibody negative (n = 10). Following statistical analysis of the longitudinal data, targeted serum proteomics was used to verify 11 proteins putatively associated with the disease development in a similar yet independent and larger cohort of children who progressed to the disease within 5 years of age (n = 31) and matched autoantibody negative children (n = 31). These data reiterated extensive age-related trends for protein levels in young children. Further, these analyses demonstrated that the serum levels of two peptides unique for apolipoprotein C1 (APOC1) were decreased after the appearance of the first islet autoantibody and remained relatively less abundant in children who progressed to type 1 diabetes, in comparison to autoantibody negative children.

show abstract

“…IgM antibodies are involved in the recognition and elimination of precancerous and cancerous lesions, have been found to be upregulated in breast cancer [ 58 ] and were considered a biomarker for recurrence [ 59 ]. IGHM also retained a significant prognostic impact on the density of intratumoural CD20+ B cells [ 60 ] and was associated with type 1 diabetes [ 61 ]. IGHM is involved in oxidative stress and in skin regeneration [ 62 ], suggesting that it may be involved in cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

Screening differentially expressed genes between endometriosis and ovarian cancer to find new biomarkers for endometriosis

Gao

2021

Annals of Medicine

View full text Add to dashboard Cite

Aim Endometriosis is one of the most common reproductive system diseases, but the mechanisms of disease progression are still unclear. Due to its high recurrence rate, searching for potential therapeutic biomarkers involved in the pathogenesis of endometriosis is an urgent issue. Methods Due to the similarities between endometriosis and ovarian cancer, four endometriosis datasets and one ovarian cancer dataset were downloaded from Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified, followed by gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and protein–protein interaction (PPI) analyses. Then, we validated gene expression and performed survival analysis with ovarian serous cystadenocarcinoma (OV) datasets in TCGA/GTEx database, and searched for potential drugs in the Drug-Gene Interaction Database. Finally, we explored the miRNAs of key genes to find biomarkers associated with the recurrence of endometriosis. Results In total, 104 DEGs were identified in the endometriosis datasets, and the main enriched GO functions included cell adhesion, extracellular exosome and actin binding. Fifty DEGs were identified between endometriosis and ovarian cancer datasets including 11 consistently regulated genes, and nine DEGs with significant expression in TCGA/GTEx. Only IGHM had both significant expression and an association with survival, three module DEGs and two significantly expressed DEGs had drug associations, and 10 DEGs had druggability. Conclusions ITGA7 , ITGBL1 and SORBS1 may help us understand the invasive nature of endometriosis, and IGHM might be related to recurrence; moreover, these genes all may be potential therapeutic targets. KEY MESSAGE This manuscript used a bioinformatics approach to find target genes for the treatment of endometriosis. This manuscript used a new approach to find target genes by drawing on common characteristics between ovarian cancer and endometriosis. We screened relevant therapeutic agents for target genes in the drug database, and performed histological validation of target genes with both expression and survival analysis difference in cancer databases.

show abstract

Immunoglobulin M gene association with autoantibody reactivity and type 1 diabetes

Cited by 6 publications

References 38 publications

Polymorphisms in canine immunoglobulin heavy chain gene cluster: a double‐edged sword for diabetes mellitus in the dog

Polymorphisms in canine immunoglobulin heavy chain gene cluster: a double‐edged sword for diabetes mellitus in the dog

Serum APOC1 levels are decreased in young autoantibody positive children who rapidly progress to type 1 diabetes

Screening differentially expressed genes between endometriosis and ovarian cancer to find new biomarkers for endometriosis

Contact Info

Product

Resources

About