Tetraspanin 7 autoantibodies in type 1 diabetes

Walther, Denise; Eugster, Anne; Jergens, Sibille; Gavrisan, Anita; Weinzierl, Christina; Telieps, Tanja; Winkler, Christiane; Ziegler, Anette G.; Bonifacio, Ezio

doi:10.1007/s00125-016-3997-1

Cited by 34 publications

(38 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This was done to reduce the likelihood of missing epitopes due to weak binding, but this selection may have introduced bias into the epitope identification. We did not, for example, identify binding to external domains of tetraspanin 7, whereas we previously found sera from individuals with type 1 diabetes to contain weak binding to these domains [7].…”

Section: Discussioncontrasting

confidence: 74%

“…Antibodies to truncated tetraspanin 7-NanoLuc fusion proteins were measured in 41 tetraspanin 7 antibody-positive serum samples from individuals with type 1 diabetes (median [range], 48.4 units/ml [5.3-342.0 units/ml]) and 20 islet autoantibody-negative serum samples [7]. Antibody binding >3 SDS was observed in serum from individuals with type 1 diabetes for the C1 (n = 16; 39%), C1-TM1 (n = 6; 15%), C1-TM1-E1 (n = 13, 32%), C1-TM1-E1-TM2 (n = 1; 2%), TM1-E1-TM2-C2 (n = 5; 12%), TM3-E2-TM4-C3 (n = 9; 22%), E2-TM4-C3 (n = 2; 5%), TM4-C3 (n = 6; 15%) and C3 (n = 8; 20%) proteins ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Participants Sera were obtained from individuals with newonset type 1 diabetes, and from islet autoantibody-negative participants in the TeenDiab cohort of prospectively followed first-degree relatives of individuals with type 1 diabetes [5,6] Tetraspanin 7 fragment and mutant proteins The truncated C1 (amino acid [AA] 1-16), C1-TM1 (AA 1-40), C1-TM1-E1-TM2 (AA 1-75), C1-TM1-E1 (AA 1-56), TM1-E1-TM2-C2 (AA 17-86), E1-TM1-C2 (AA 41-86), C2 (AA 76-86), TM2-C2-TM3-E2 (AA 57-213), C2-TM3-E2 (AA 76-213), TM3-E2-TM4-C3 (AA 87-249), E2-TM4-C3 (AA 113-249), TM4-C3 (AA 214-249) and C3 (AA 235-249) tetraspanin 7 fragments NH 2 -terminally fused to NanoLuc were constructed by PCR amplification from full-length tetraspanin 7 [7] and cloning into pCMV6-AC-IRES-GFP-Puro (Origene, Rockville, MD, USA) containing NanoLuc. Mutations at the C3 residues of the NanoLuc-TM3-E2-TM4-C3 construct were introduced using QuickChange Site-directed Mutagenesis (Agilent, Santa Clara, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Cytoplasmic ends of tetraspanin 7 harbour epitopes recognised by autoantibodies in type 1 diabetes

et al. 2019

Self Cite

View full text Add to dashboard Cite

Aims/hypothesis The beta cell protein tetraspanin 7 is a target of autoantibodies in individuals with type 1 diabetes. The aim of this study was to identify autoantibody epitope-containing regions and key residues for autoantibody binding. Methods Autoantibody epitope regions were identified by immunoprecipitation of luciferase-tagged single or multiple tetraspanin 7 domains using tetraspanin 7 antibody-positive sera. Subsequently, amino acids (AAs) relevant for autoantibody binding were identified by single AA mutations. Results In tetraspanin 7 antibody-positive sera, antibody binding was most frequent to tetraspanin 7 proteins that contained the NH 2 -terminal cytoplasmic domain 1 (C1; up to 39%) or COOH-terminal C3 (up to 22%). Binding to C3 was more frequent when the domain was expressed along with the flanking transmembrane domain, suggesting that conformation is likely to be important. Binding to external domains was not observed. Single AA mutations of C3 identified residues Y246, E247 and R239 as critical for COOH-terminal binding of 9/10, 10/10 and 8/10 sera tested, respectively. Mutation of cysteines adjacent to the transmembrane domain at either residues C235 or C236 resulted in both decreased (8/178 and 15/178 individuals, respectively; >twofold decrease) and increased (30/178 and 13/178 individuals, respectively; >twofold increase) binding in participant sera vs wild-type protein. Conclusions/interpretationWe hypothesise that conformation and, potentially, modification of protein terminal ends of tetraspanin 7 may be important for autoantibody binding in type 1 diabetes.

show abstract

Section: Discussioncontrasting

confidence: 74%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Cytoplasmic ends of tetraspanin 7 harbour epitopes recognised by autoantibodies in type 1 diabetes

et al. 2019

Self Cite

View full text Add to dashboard Cite

show abstract

“…In contrast, the β cell zinc transporter 8 (ZnT8) protein has been confirmed to be a target of autoantibodies (ZnT8A) in more than 50% of patients with type 1 diabetes , and tetraspanin 7 was identified as the 38‐kDa target of autoantibodies against glima . These autoantibodies were present in more than 30% of patients with type 1 diabetes .…”

Section: Historical Perspectivesmentioning

confidence: 99%

Birth and coming of age of islet autoantibodies

Bonifacio

Achenbach

2019

Clinical and Experimental Immunology

View full text Add to dashboard Cite

show abstract

“…Tetraspanin-7 is a newly confirmed T1DM autoantigen [23]. The autoantibody TSPAN7A is more frequently detected together with GADA, IA-2A, or ZnT8A than alone [24]. In this study, among 35 T1DM patients negative for GADA, IA-2A, and ZnT8A, 5 screened positive for TSPAN7A, indicating that T1DM may be associated with TSPAN7A alone in a minority of Chinese patients.…”

Section: Discussionmentioning

confidence: 53%

Organ-specific autoantibodies in Chinese patients newly diagnosed with type 1 diabetes mellitus

Pan

Shi

et al. 2020

Endocr J

View full text Add to dashboard Cite

This study aims to investigate the prevalence of islet autoantibodies and other organ-specific autoantibodies in type 1 diabetes mellitus (T1DM) patients and characterize their clinical features. Glutamic acid decarboxylase antibody (GADA), insulinoma antigen 2 antibody (IA-2A), zinc transporter 8 antibody (ZnT8A) and tetraspanin7 antibody (TSPAN7A) were assayed by radioligand or luciferase immunoprecipitation system assays in 205 newly diagnosed acute-onset T1DM patients and 170 healthy controls. Other organ-specific autoantibodies, including thyroid peroxidase antibody (TPOA), thyroglobulin antibody (TGA), tissue transglutaminase antibody (tTGA) and 21-hydroxylase antibody (21-OHA), were also measured. The prevalence of GADA, IA-2A, ZnT8A, TSPAN7A, TPOA, TGA and 21-OHA was higher in T1DM patients than in healthy controls. The combinational assay of various islet autoantibodies could increase the frequency of autoantibody positivity in T1DM to 85.4%. GADA+ IA-2A+ T1DM patients preferentially had TPOA and TGA, while IA-2A+ patients often had tTGA. Patients positive for two or more islet autoantibodies often had TPOA and TGA. BMI of multiple islet autoantibodypositive patients was lower than that of patients with single or no islet autoantibodies, and there were no significant differences in C-peptide and glycated hemoglobin between patients positive for islet autoantibodies combined with other organ-specific antibodies and noncombined patients. Younger female patients who were islet autoantibody positive were more likely to have TPOA and TGA. The frequency of Graves' disease was much higher in T1DM patients than in healthy controls. T1DM usually occurs together with other organ-specific autoantibodies. Measuring of other organ-specific autoantibodies will be beneficial for T1DM patients.

show abstract

Tetraspanin 7 autoantibodies in type 1 diabetes

Cited by 34 publications

References 7 publications

Cytoplasmic ends of tetraspanin 7 harbour epitopes recognised by autoantibodies in type 1 diabetes

Cytoplasmic ends of tetraspanin 7 harbour epitopes recognised by autoantibodies in type 1 diabetes

Birth and coming of age of islet autoantibodies

Organ-specific autoantibodies in Chinese patients newly diagnosed with type 1 diabetes mellitus

Contact Info

Product

Resources

About