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Antigen-based vs. systemic immunomodulation in type 1 diabetes: the pros and cons.

ABSTRACT: In type 1 diabetic patients insulin-producing pancreatic ?-cells are destroyed by an orchestrated immune process involving self-reactive auto-antigen-specific CD4? and CD8? T cells. Efforts to reverse or prevent this destructive immunological cascade have led to promising results in animal models, however, the transition to the clinic has yet been unsuccessful. In addition, current clinical studies lack reliable biomarkers to circumscribe end-point parameters and define therapeutic success. Here, we give a current overview of both antigen-specific and non-specific systemic immunomodulatory approaches with a focus on the therapies verified or under evaluation in a clinical setting. While both approaches have their advantages and disadvantages, rationally designed combination therapies may yield the highest therapeutic efficacy. In order for future strategies to be effective, new well-defined biomarkers need to be developed and the extrapolation process of dose, timing and frequency from in vivo models to patients needs to be carefully reconsidered.

SUBMITTER: Robert S

PROVIDER: S-EPMC4204023 | biostudies-literature | 2013 Mar-Apr

REPOSITORIES: biostudies-literature

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Antigen-based vs. systemic immunomodulation in type 1 diabetes: the pros and cons.

Robert Sofie S Korf Hannelie H Gysemans Conny C Mathieu Chantal C

Islets 20130301 2

In type 1 diabetic patients insulin-producing pancreatic β-cells are destroyed by an orchestrated immune process involving self-reactive auto-antigen-specific CD4⁺ and CD8⁺ T cells. Efforts to reverse or prevent this destructive immunological cascade have led to promising results in animal models, however, the transition to the clinic has yet been unsuccessful. In addition, current clinical studies lack reliable biomarkers to circumscribe end-point parameters and define therapeutic success. Here ...[more]

PMID: 23648893

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Project description:ObjectivesLong-term effects of gastric bypass (GBP) surgery have been presented in observational and randomised studies, but there are only limited data for persons with obesity and type 2 diabetes mellitus (T2DM) regarding postoperative complications.DesignThis is a nationwide observational study based on two quality registers in Sweden (National Diabetes Register, NDR and Scandinavian Obesity Surgery Register, SOReg) and other national databases.SettingAfter merging the data, we matched individuals with T2DM who had undergone GBP with those not surgically treated for obesity on propensity score, based on sex, age, body mass index (BMI) and calendar time. The risks of postoperative outcomes (rehospitalisations) were assessed using Cox regression models.ParticipantsWe identified 5321 patients with T2DM in the SOReg and 5321 matched controls in the NDR, aged 18-65 years, with BMI >27.5 kg/m² and followed for up to 9 years.Primary and secondary outcome measuresWe assessed risks for all-cause mortality and hospitalisations for cardiovascular disease, severe kidney disease, along with surgical and other medical conditions.ResultsThe results agree with the previously suggested lower risks of all-cause mortality (49%) and cardiovascular disease (34%), and we also found positive effects for severe kidney disease but significantly increased risks (twofold to ninefold) of several short-term complications after GBP, such as abdominal pain and gastrointestinal conditions, frequently requiring surgical procedures, apart from reconstructive plastic surgery. Long-term, the risk of anaemia was 92% higher, malnutrition developed approximately three times as often, psychiatric diagnoses were 33% more frequent and alcohol abuse was three times as great as in the control group.ConclusionsThis nationwide study confirms the benefits and describes the panorama of adverse events after bariatric surgery in persons with obesity and T2DM. Long-term postoperative monitoring and support, as better selection of patients by appropriate specialists in interdisciplinary settings, should be provided to optimise the outcomes.

Dataset Information

Antigen-based vs. systemic immunomodulation in type 1 diabetes: the pros and cons.

Publications

Antigen-based vs. systemic immunomodulation in type 1 diabetes: the pros and cons.

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