Gheorghiu Mihaela, Trandafir Maria-Florina, Savu Octavian, Pasarica Daniela, Bleotu Coralia
Pathophysiology and Immunology Department, "Carol Davila" University of Medicine and Pharmacy, 020021 Bucharest, Romania.
"N.C. Paulescu" National Institute of Diabetes, Nutrition and Metabolic Diseases, 020475 Bucharest, Romania.
J Clin Med. 2025 Apr 8;14(8):2556. doi: 10.3390/jcm14082556.
The case we present is part of a large study that we conducted on hemodialysis patients with type 2 diabetes mellitus (T2DM) and which set the following objectives: studying changes in the intestinal microbiota, innate and acquired immune response capacity, and tissue regeneration. (1) For the genetic study of the gut microbiota, special techniques that are not based on cultivation were used since most of the species in the intestinal flora are not cultivable. (2) The immunological study had two targets: innate immunity (inflammation) and adaptive immunity (we chose to address the cellular immune response because, unlike the humoral one, it is insufficiently studied in this category of associated pathologies). As markers for innate immunity (inflammation), the following were determined: IL-6, sIL-6R, IL-1β, TNFα, IL-10, and NGAL. TNFβ/LTα was determined as a marker for adaptive immunity (the cellular immune response). (3) The study of tissue regeneration capacity was performed using NT-3 (this is the first study to do so) and VEGFβ (another marker that is scarce in this category of patients) as markers. All the aforementioned compounds were determined from serum samples, utilizing Merck Millipore ELISA kits for IL-6, IL-1β, IL-10, NT-3, and VEGF β, and Elabscience ELISA kits for IL-6R, TNFα, TNFβ, and NGAL. We were very surprised to find unexpected immunological changes and tissue regenerative capacity in one of the patients studied, an 82-year-old female patient diagnosed with insulin-dependent T2DM with multiple complications, including end-stage renal disease (ESRD). The patient showed a huge capacity for tissue regeneration, combined with amplification of immunological capacity, in comparison to patients in the same group (T2DM and ESRD) and to those in the control group (ESRD). Thus, extremely elevated serum concentrations of IL-1β, IL-6, IL-10, and TNF-β, as well as the tissue regeneration indicators NT-3 and VEGFβ, were obtained in comparison to all other members of the patient group. At the same time, serum levels of the soluble IL-6 receptor (sIL6-R) and TNFα were greatly reduced compared to the test group's mean. All the data obtained during our research were corroborated with those from the specialized literature and entitle us to support the hypothesis that the cause of these unexpected behaviors is the genetically conditioned overproduction (possibly acquired post-infection) of IL-6, along with its predominant anti-inflammatory and pro-regenerative signaling through the membrane-bound receptor IL-6R.
我们呈现的这个病例是我们针对2型糖尿病（T2DM）血液透析患者开展的一项大型研究的一部分，该研究设定了以下目标：研究肠道微生物群的变化、先天性和获得性免疫反应能力以及组织再生情况。（1）对于肠道微生物群的基因研究，采用了不基于培养的特殊技术，因为肠道菌群中的大多数物种无法培养。（2）免疫学研究有两个目标：先天性免疫（炎症）和适应性免疫（我们选择研究细胞免疫反应，因为与体液免疫不同，在这类相关病症中对其研究不足）。作为先天性免疫（炎症）的标志物，测定了以下指标：IL-6、sIL-6R、IL-1β、TNFα、IL-10和NGAL。TNFβ/LTα被测定为适应性免疫（细胞免疫反应）的标志物。（3）使用NT-3（这是首次这样做的研究）和VEGFβ（这类患者中另一种稀缺的标志物）作为标志物来研究组织再生能力。所有上述化合物均从血清样本中测定，使用默克密理博ELISA试剂盒检测IL-6、IL-1β、IL-10、NT-3和VEGFβ，使用Elabscience ELISA试剂盒检测IL-6R、TNFα、TNFβ和NGAL。我们非常惊讶地发现在所研究的一名患者中出现了意想不到的免疫变化和组织再生能力，该患者是一名82岁的女性，被诊断为胰岛素依赖型T2DM，伴有多种并发症，包括终末期肾病（ESRD）。与同一组（T2DM和ESRD）的患者以及对照组（ESRD）的患者相比，该患者表现出巨大的组织再生能力，同时免疫能力增强。因此，与患者组的所有其他成员相比，该患者血清中IL-1β、IL-6、IL-10和TNF-β以及组织再生指标NT-3和VEGFβ的浓度极高。与此同时，与测试组的平均值相比，可溶性IL-6受体（sIL6-R）和TNFα的血清水平大幅降低。我们在研究过程中获得的所有数据都得到了专业文献数据的证实，这使我们能够支持这样一种假设，即这些意外行为的原因是IL-6的基因决定的过量产生（可能是感染后获得的），以及它通过膜结合受体IL-6R进行的主要抗炎和促再生信号传导。
