Serological short-chain fatty acid and trimethylamine N-oxide microbial metabolite imbalances in young adults with acute myocardial infarction.

Acute myocardial infarction (AMI) is associated with systemic inflammatory processes and metabolic alterations. Microbial-derived metabolites, such as short-chain fatty acids and trimethylamine N-oxide (TMAO), have emerged in recent years as key players in the modulation of inflammation, with potential implications for cardiovascular diseases. We performed a prospective observational study that monitored the serological concentration of bacterial metabolites in 45 young patients (<55 years) without cardiovascular risk factors but with AMI, at hospital admission and at 3 months of follow-up, and compared them with a control group. TMAO and acetate levels were significantly higher in AMI, whereas butyrate and propionate were significantly lower. The acetate/propionate ratio showed the most discrimination between AMI and controls by receiver operating characteristic analysis (area under the curve 0.769, P < 0.0001). A multivariate logistic regression model revealed that this ratio was independently associated with AMI. Short-chain fatty acid concentrations, but not TMAO, exhibited significant correlations with inflammatory and coagulation parameters. Three months after the acute AMI event, all metabolite levels returned to those observed in healthy controls except butyrate. In conclusion, our study reveals disturbances of the serological concentration of microbiota-derived metabolites in AMI that are also related to inflammatory and coagulation parameters. These findings highlight an interesting field of study in the potential role of microbial metabolites from gut in cardiovascular disease.

Development and validation of a clinical score for identifying patients with high risk of latent autoimmune adult diabetes (LADA): The LADA primary care-protocol study.

BACKGROUND: Latent autoimmune diabetes in adults (LADA) is a type of diabetes mellitus showing overlapping characteristics between type 1 Diabetes Mellitus and type 2 Diabetes Mellitus (T2DM), and autoimmunity against insulin-producing pancreatic cells. For its diagnosis, at least one type of anti-pancreatic islet antibody (GADAb is the most common) is required. Many authors recommend performing this measure in all newly diagnosed patients with DM, but it is not possible in Primary Health Care (PHC) due to its high cost. Currently, a relevant proportion of patients diagnosed as T2DM could be LADA. Confusing LADA with T2DM has clinical and safety implications, given its different therapeutic approach. The main objective of the study is to develop and validate a clinical score for identifying adult patients with DM at high risk of LADA in PHC. METHODS: This is an observational, descriptive, cross-sectional study carried out in Primary Care Health Centers with a centralized laboratory. All people over 30 years of age diagnosed with diabetes within a minimum of 6 months and a maximum of 4 years before the start of the study will be recruited. Individuals will be recruited by consecutive sampling. The study variables will be obtained through clinical interviews, physical examinations, and electronic medical records. The following variables will be recorded: those related to Diabetes Mellitus, sociodemographic, anthropometric, lifestyle habits, laboratory parameters, presence of comorbidities, additional treatments, personal or family autoimmune disorders, self-perceived health status, Fourlanos criteria, and LADA diagnosis (as main variable) according to current criteria. DISCUSSION: The study will provide an effective method for identifying patients at increased risk of LADA and, therefore, candidates for antibody testing. However, a slight participation bias is to be expected. Differences between participants and non-participants will be studied to quantify this potential bias.

Evaluation of the new Abbott®Alinity assay for the measurement of thyroglobulin antibodies in patients with differentiated thyroid carcinoma.

BACKGROUND: Measurement of antithyroglobulin antibodies (TgAb) is important in patients with differentiated thyroid carcinoma (DTC) with total thyroidectomy. These patients are monitored based on serum thyroglobulin (Tg) levels. TgAb is known to interfere with the measurement of Tg by immunoassay. This study evaluates a new methodology for the measurement of TgAb Alinity Abbott® and the concordance with other methods (first and second generation Advia Centaur Systems Siemens® and Phadia 250 Thermofisher®). METHODS: The technical characteristics of Alinity TgAb measurement methodology were analysed, with imprecision and repeatable studies. In order to assess concordance, a minimum of 69 and a maximum of 76 samples from patients with DTC and total thyroidectomy were processed in parallel by several TgAb measurement methodologies. Agreement rates were determined using kappa statistics. The correlation between the four methods was examined pairwise using McNemar test analysis. RESULTS: The coefficients of variation (standard deviation as a percentage of the mean % CV) for the Alinity Abbott kit reagent TgAb were within 10% included the functional sensitivity. On the other hand, the concordance analysis with the kappa index concluded substantial agreement. The McNemar test showed a significant difference between Alinity versus Centaur second generation (difference 8.33%, CI 95% 0.68-8.33, p = .0313). CONCLUSION: The new methodology for the measurement of TgAb meets the imprecision standards while presenting an adequate concordance agreement with other methodologies available in laboratories. It is important to define the functional sensitivity when reporting results so that they are as reliable as possible.

Revisiting immunological and clinical aspects of membranous nephropathy.

Idiopathic or primary membranous nephropathy (IMN) is one of the most frequent causes of nephrotic syndrome in adults and the elderly. It is characterized by a thickening of the wall of the glomerular capillaries due to the presence of immune complex deposits. 85% of membranous nephropathy cases are classified as primary or idiopathic (IMN). The rest are of secondary origin (SMN), caused by autoimmune conditions or malignant tumors as lung cancer, colon and melanomas. It is an organ-specific autoimmune disease in which the complement system plays an important role with the formation of the membrane attack complex (MAC; C5b-9), which produces an alteration of the podocyte structure. The antigen responsible for 70-80% of IMN is a podocyte protein called M-type phospholipase A2 receptor (PLA2R). More recently, another podocyte antigen has been identified, the "Thrombospondin type-1 domain-containing 7A" (THSD7A), which is responsible for 10% of the cases of negative IMN for anti- PLA2R.

Role of B Cell Profile for Predicting Secondary Autoimmunity in Patients Treated With Alemtuzumab.

Objective: To explore if baseline blood lymphocyte profile could identify relapsing remitting multiple sclerosis (RRMS) patients at higher risk of developing secondary autoimmune adverse events (AIAEs) after alemtuzumab treatment. Methods: Multicenter prospective study including 57 RRMS patients treated with alemtuzumab followed for 3.25 [3.5-4.21] years, (median [interquartile range]). Blood samples were collected at baseline, and leukocyte subsets determined by flow cytometry. We had additional samples one year after the first cycle of alemtuzumab treatment in 39 cases. Results: Twenty-two patients (38.6%) developed AIAEs during follow-up. They had higher B-cell percentages at baseline (p=0.0014), being differences mainly due to plasmablasts/plasma cells (PB/PC, p=0.0011). Those with no AIAEs had higher percentages of CD4+ T cells (p=0.013), mainly due to terminally differentiated (TD) (p=0.034) and effector memory (EM) (p=0.031) phenotypes. AIAEs- patients also showed higher values of TNF-alpha-producing CD8+ T cells (p=0.029). The percentage of PB/PC was the best variable to differentiate both groups of patients. Baseline values >0.10% closely associated with higher AIAE risk (Odds ratio [OR]: 5.91, 95% CI: 1.83-19.10, p=0.004). When excluding the 12 patients with natalizumab, which decreases blood PB/PC percentages, being the last treatment before alemtuzumab, baseline PB/PC >0.1% even predicted more accurately the risk of AIAEs (OR: 11.67, 95% CI: 2.62-51.89, p=0.0007). The AIAEs+ group continued having high percentages of PB/PC after a year of alemtuzumab treatment (p=0.0058). Conclusions: A PB/PC percentage <0.1% at baseline identifies MS patients at low risk of secondary autoimmunity during alemtuzumab treatment.​.

Comparison of 3 anti-PLA2R inmmunoassaysfor the diagnosis of idiopathic membranous nephropathy in an european population. A pilot study.

Membranous nephropathy (MN) is one of the most frequent causes of nephrotic syndrome. Renal biopsy is nowadays the gold standard for the diagnosis of MN. The presence of circulating PLA2R antibody is a very specific tool for the diagnosis of this disease, especially associated with primary or idiopathic MN (IMN), even though it can be also found in a small proportion of patients with secondary MN (SMN). This pilot study compares three different techniques for the detection of anti-PLA2R autoantibodies (immunofluorescence, ELISA immunoassay, and multiplex laser bead technology). Serum of 12 IMN and 9 SMN patients was obtained at diagnosis. Additionally, we employed serum samples of 15 healthy volunteers. From our patient cohort, we obtained a 7.75 RU/ml cut-off for the ELISA and 3104 MFI for the Luminex assays. The agreement between the three techniques improved considerably when applying the new cut-off points. As several authors have suggested, cut-offs may be calculated for each specific population instead of establishing global cut-off points. Patients with IMN showed significantly lower serum albumin levels and higher 24 h proteinuria compared to those with SMN. Analysis of ROC curves suggests that ELISA and LUMINEX assays are more useful than biochemical variables to differentiate patients with IMN and SMN. This pilot study contributes to confirming that the combination of ELISA and Luminex assays provide excellent sensitivity and specificity for the identification of IMN.

Anti-N-Methyl-D-Aspartate Encephalitis as Paraneoplastic Manifestation of Germ-Cells Tumours: A Cases Report and Literature Review.

Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is the most common form of autoimmune encephalitis, caused by the interaction between an antibody and its target, located on glutamate receptor type N-methyl-D-aspartate (NMDA) of neuronal surface. There is a wide spectrum of clinical features starting by a viral-like prodrome, followed by symptoms such as psychosis, aggressive behaviour, memory loss, seizures, movement disorders, and autonomic instability. Up to 50% of the affected young female patients have germ-cells tumours as ovarian teratoma, making it essential to establish an early diagnosis through detection of specific antibodies in serum and cerebrospinal fluid (CSF). This retrospective observational study was performed in patients whom positive anti-NMDA receptor antibodies have been tested, associated with clinical manifestations that suggest autoimmune encephalitis and a germ-cell tumour confirmed by pathology. Six patients have tested positive for anti-NMDA receptor antibodies associated with a germ-cell tumour and clinical manifestations of autoimmune encephalitis. Management includes aggressive immunosuppression and surgical removal.

Association of anti-Yo, anti-Hu and antiSOX1 antibodies in CSF in a patient with limbic and paralimbic encephalitis in the setting of small cell lung carcinoma: case presentation with review of the literatura

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