A 1-year pilot study of intralymphatic injections of GAD-alum in individuals with latent autoimmune diabetes in adults (LADA) with signs of high immunity: No safety concerns and resemblance to juvenile type 1 diabetes

IF 5.4 2区医学 Q1 ENDOCRINOLOGY & METABOLISM Diabetes, Obesity & Metabolism Pub Date : 2023-08-14 DOI:10.1111/dom.15239

Ingrid K. Hals PhD, Chandima Balasuriya MD, Rosaura Casas PhD, Johnny Ludvigsson MD, Anneli Bj?rklund MD, Valdemar Grill MD

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Abstract

Aims

To test, for the first time in latent autoimmune diabetes in adults (LADA), the effects of autoantigen-specific immunotherapy by intralymphatic administration of aluminium-formulated recombinant human glutamic acid decarboxylase 65 (GAD-alum); specifically, to test if this treatment is safe, to test whether it induces a strong immunological response akin to a similar protocol in type 1 diabetes and to look for associations with preserved beta-cell function.

Materials and Methods

Three GAD-alum injections, 4 μg each, were administered 1 month apart into an inguinal lymph node in 14 people with newly diagnosed LADA (age 30-62 years) presenting with high levels of antibodies against glutamic acid decarboxylase (GADA). Adverse effects, immunological variables and beta-cell function were monitored, with detailed measurements at 5 and 12 months from baseline.

Results

Clinical adverse effects were minor and transient and measured laboratory variables were unaffected. All participants completed the study. Treatment raised levels of GADA, elicited strong effects on reactivity of peripheral blood mononuclear cells to GAD and raised cytokine/chemokine levels. Beta-cell function appeared stable preferentially in the seven participants carrying human leukocyte antigen (HLA) haplotypes DR3DQ2, as assessed by C-peptide glucagon tests (P < 0.05 vs. seven non-carriers).

Conclusion

Intralymphatic treatment with GAD-alum in LADA is without clinical or other safety concerns over a 12-month period. As in a similar protocol used in type 1 diabetes, treatment exerts a strong immunological impact and is compatible with protection of beta-cell function preferentially in HLA-DR3DQ2 LADA patients. These findings pave the way for a randomized controlled trial in this important subgroup of LADA patients.

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GAD明矾在有高免疫力迹象的成人潜在自身免疫性糖尿病（LADA）患者淋巴管内注射的1年试点研究：无安全问题，与青少年1型糖尿病相似

目的首次在成人潜伏性自身免疫性糖尿病（LADA）中，通过淋巴管内给药铝配制的重组人谷氨酸脱羧酶65（GAD明矾）来测试自身抗原特异性免疫疗法的效果；具体来说，测试这种治疗是否安全，测试它是否诱导类似于1型糖尿病类似方案的强烈免疫反应，并寻找与保留的β细胞功能的相关性。材料和方法三种GAD明矾注射液，4 μg，给药1 14名新诊断的LADA患者（年龄30-62岁）的腹股沟淋巴结间隔一个月年），呈现高水平的抗谷氨酸脱羧酶（GADA）抗体。监测不良反应、免疫变量和β细胞功能，并在5岁和12岁时进行详细测量月。结果临床不良反应轻微且为短暂性，实验室测量变量不受影响。所有参与者都完成了研究。治疗提高了GADA水平，对外周血单核细胞对GAD的反应性产生了强烈影响，并提高了细胞因子/趋化因子水平。通过C-肽胰高血糖素测试评估，携带人类白细胞抗原（HLA）单倍型DR3DQ2的7名参与者的β细胞功能优先稳定（P <； 0.05对七个非携带者）。结论GAD明矾在LADA的淋巴管内治疗12个月内没有临床或其他安全问题。与用于1型糖尿病的类似方案一样，治疗具有强大的免疫影响，并且优先与HLA-DR3DQ2 LADA患者的β细胞功能保护相容。这些发现为LADA患者这一重要亚组的随机对照试验铺平了道路。

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来源期刊

Diabetes, Obesity & Metabolism 医学-内分泌学与代谢

CiteScore

10.90

自引率

6.90%

发文量

319

审稿时长

3-8 weeks

期刊介绍： Diabetes, Obesity and Metabolism is primarily a journal of clinical and experimental pharmacology and therapeutics covering the interrelated areas of diabetes, obesity and metabolism. The journal prioritises high-quality original research that reports on the effects of new or existing therapies, including dietary, exercise and lifestyle (non-pharmacological) interventions, in any aspect of metabolic and endocrine disease, either in humans or animal and cellular systems. ‘Metabolism’ may relate to lipids, bone and drug metabolism, or broader aspects of endocrine dysfunction. Preclinical pharmacology, pharmacokinetic studies, meta-analyses and those addressing drug safety and tolerability are also highly suitable for publication in this journal. Original research may be published as a main paper or as a research letter.