Mucosal Immune Defence Gene Polymorphisms as Relevant Players in the Pathogenesis of IgA Vasculitis?

ITGAM-ITGAX (rs11150612, rs11574637), VAV3 rs17019602, CARD9 rs4077515, DEFA (rs2738048, rs10086568), and HORMAD2 rs2412971 are mucosal immune defence polymorphisms, that have an impact on IgA production, described as risk loci for IgA nephropathy (IgAN). Since IgAN and Immunoglobulin-A vasculitis (IgAV) share molecular mechanisms, with the aberrant deposit of IgA1 being the main pathophysiologic feature of both entities, we assessed the potential influence of the seven abovementioned polymorphisms on IgAV pathogenesis. These seven variants were genotyped in 381 Caucasian IgAV patients and 997 matched healthy controls. No statistically significant differences were observed in the genotype and allele frequencies of these seven polymorphisms when the whole cohort of IgAV patients and those with nephritis were compared to controls. Similar genotype and allele frequencies of all polymorphisms were disclosed when IgAV patients were stratified according to the age at disease onset or the presence/absence of gastrointestinal or renal manifestations. Likewise, no ITGAM-ITGAX and DEFA haplotype differences were observed when the whole cohort of IgAV patients, along with those with nephritis and controls, as well as IgAV patients, stratified according to the abovementioned clinical characteristics, were compared. Our results suggest that mucosal immune defence polymorphisms do not represent novel genetic risk factors for IgAV pathogenesis.

High Pretransplant BAFF Levels and B-cell Subset Polarized towards a Memory Phenotype as Predictive Biomarkers for Antibody-Mediated Rejection.

Antibody-mediated rejection (AbMR) is one of the leading causes of graft loss in kidney transplantation and B cells play an important role in the development of it. A B-cell activating factor (BAFF) is a cytokine involved in B cell ontogeny. Here, we analyzed whether B cell maturation and the effect of B cell soluble factors, such as BAFF could be involved in AbMR. Serum BAFF levels and B and T cell subpopulations were analyzed 109 kidney transplant patients before transplantation and at 6 and 12 months after kidney transplantation. Pretransplant serum BAFF levels as well as memory B cell subpopulations were significantly higher in those patients who suffered clinical AbMR during the first 12 months after kidney transplantation. Similar results were observed in the prospective analysis of patients with subclinical antibody-mediated rejection detected in the surveillance biopsy performed at 12 months after kidney transplantation. A multivariate analysis confirmed the independent role of BAFF in the development of AbMR, irrespective of other classical variables. Pretransplant serum BAFF levels could be an important non-invasive biomarker for the prediction of the development of AbMR and posttransplant increased serum BAFF levels contribute to AbMR.

Low-risk delisting strategy in highly sensitized patients without donor offers included in exchange donation programs. One single-center experience.

Donor exchange programs were designed to allocate organs for highly sensitized (HS) patients. The allocation algorithm differs slightly among countries and includes different strategies to improve access to transplants in HS patients. However, many HS patients with a calculated panel reactive of antibodies (cPRA) of 100 % remain on the waiting list for a long time. Some allocation algorithms assume immunological risk, including Imlifidase treatment, to increase the chance of transplantation in very HS patients. Here, we describe our unicenter experience of low-risk delisting strategy in 15 HS patients included in the Spanish donor exchange program without donor offers. After delisting, 7 out of 15 HS patients reduced the cPRA below 99.95 % and impacted the reduction of time on the waiting list (p = 0.01), where 5 out of 7 achieved transplantation. Within those HS that remained above 99.95 %, 1 out of 8 was transplanted. All the HS were transplanted with delisted DSA, and only one with DSA level rebounded early after transplantation. All HS transplanted after delisting maintain graft function. The transplant immunology laboratories are challenged to search intermediate risk assessment methods for delisting high HS patients.

Association of severe preeclampsia and vascular damage assessed by noninvasive markers of arterial stiffness.

BACKGROUND: Preeclampsia (PE) is a hypertensive disorder of pregnancy associated with high maternal and fetal morbidity and mortality and increased future risk of cardiovascular complications. OBJECTIVE: To analyze whether women who have had PE with severe features in their pregnancy have higher arterial stiffness (AS) parameters than those whose PE course was without signs of severity. METHODS: Sixty-five women who developed PE during their gestation were evaluated, divided into two groups: PE group without severe features or non-severe PE (n=30) and PE group with severe features or severe PE (n=35). Carotid-femoral pulse wave velocity (cfPWV), central augmentation index corrected to a heart rate of 75 beats per minute (AIxc75) and central augmentation pressure (cAP) were determined one month and six months postpartum. Comparison of proportions was carried out using the chi-square test, comparison of means between groups using the Student's t-test or the Mann-Whitney test, and comparison of means of the same group at different evolutionary moments, using the t-test or the Wilcoxon test. Correlation, with and between hemodynamic parameters, was carried out with Spearman's correlation coefficient and the association between demographic variables, personal history and hemodynamic parameters, and altered arterial stiffness parameters was carried out using linear and logistic regression models. RESULTS: Women with severe PE presented, both at 1 and 6 months postpartum, higher values of blood pressure, both central and peripheral, as well as AR and pulse amplification parameters, than those women whose PE was not severe. Central augmentation index (cAIx) values at 1 month and 6 months postpartum were higher, although not significantly, in the severe PE group compared to the non-severe PE group (24.0 (16.5-34.3) vs. 19.0% (14-29) and 24.0 (14.0-30.0) vs. 20.0% (12.3-26.8), respectively). Carotid-femoral pulse wave velocity (cfPWV) was significantly higher at both 1 and 6 months postpartum in the severe PE group compared to the non-severe PE group (10.2 (8.8-10.7) vs. 8.8m/s (8.3-9.6) and 10.0 (8.8-10.6) vs. 8.8m/s (8.3-9.3), respectively). Central systolic pressure and central pulse pressure amplification were also higher, although not significantly, in the severe PE group in comparison with the non-severe PE group. CONCLUSIONS: Women who have had severe PE have more pronounced arterial stiffness parameters than those in whom PE was not particularly severe. The determination of cAIx and cfPWV, as a strategy for the assessment of cardiovascular risk, should be evaluated among women who have had PE.

Increased induction of de novo serum ANCA and ANCA-associated vasculitis after mass vaccination against SARS-CoV-2.

Different immune-mediated diseases have been described after SARS-CoV-2 vaccination, with antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) being one of the possible side effects. In this study, a total of 35 patients presented ANCA for the first time during 2021, with the number during 2019 being 15. Twenty-seven out of thirty-five patients developed ANCA after vaccination. Two of them developed these antibodies after receiving the first dose (7.4%), and 25 patients developed ANCA after the second dose of the vaccine (92.6%), with BNT162b2 being the main vaccine received by these patients. In 97.1% of the patients who developed ANCA during 2021, the positivity of ANCA was accompanied by systemic involvement, with renal and respiratory tracts being the main organs affected. Therefore, an increase in the development of AAV has been observed during 2021 in comparison with 2019, which could be due to the administration of SARS-CoV-2 vaccine.

IgA Vasculitis: Influence of CD40, BLK and BANK1 Gene Polymorphisms.

CD40, BLK and BANK1 genes involved in the development and signaling of B-cells are identified as susceptibility loci for numerous inflammatory diseases. Accordingly, we assessed the potential influence of CD40, BLK and BANK1 on the pathogenesis of immunoglobulin-A vasculitis (IgAV), predominantly a B-lymphocyte inflammatory condition. Three genetic variants within CD40 (rs1883832, rs1535045, rs4813003) and BLK (rs2254546, rs2736340, rs2618476) as well as two BANK1 polymorphisms (rs10516487, rs3733197), previously associated with inflammatory diseases, were genotyped in 382 Caucasian patients with IgAV and 955 sex- and ethnically matched healthy controls. No statistically significant differences were observed in the genotype and allele frequencies of CD40, BLK and BANK1 when IgAV patients and healthy controls were compared. Similar results were found when CD40, BLK and BANK1 genotypes or alleles frequencies were compared between patients with IgAV stratified according to the age at disease onset or to the presence/absence of gastrointestinal or renal manifestations. Moreover, no CD40, BLK and BANK1 haplotype differences were disclosed between patients with IgAV and healthy controls and between patients with IgAV stratified according to the clinical characteristics mentioned above. Our findings indicate that CD40, BLK and BANK1 do not contribute to the genetic background of IgAV.

Non-Criteria Antiphospholipid Antibodies: Risk Factors for Endothelial Dysfunction in Women with Pre-Eclampsia.

The association between unconventional antiphospholipid antibodies and pre-eclampsia in patients without thrombotic manifestations and its relationship with endothelial dysfunction after delivery has been studied poorly. We included 157 pregnant women, 122 of them having developed pre-eclampsia (56 non-severe and 66 severe). The determination of classical and unconventional, as well as pulse wave velocity and ankle-brachial index were performed at three months after delivery. The prevalence of unconventional antiphospholipid antibodies was 22.9% and 54.9% in patients included in control and pre-eclampsia groups, respectively (p = 0.001). The most frequent antiphospholipid antibody was IgM anti-phosphatidylserine/prothrombin in both cohorts. The presence of IgM anti-phosphatidylserine/prothrombin showed an association with the development of pre-eclampsia (OR = 5.4; CI 95% (2.0-14.9), p = 0.001) with an AUC of 0.744 (p < 0.001). Likewise, IgM anti-phosphatidylserine/prothrombin exhibited a positive linear correlation with pulse wave velocity values (rho = 0.830; p < 0.001) and an association with the presence of pulse wave velocity altered values (OR = 1.33; CI95% (1.10-1.59), p = 0.002). With regard to ankle braquial index values, the presence of IgM anti-phosphatidylserine/prothrombin displayed a weak negative correlation (rho = -0.466; p < 0.001) and an association with altered ankle braquial index values (OR = 1.08; CI 95% (1.04-1.13), p < 0.001). In patients who developed preeclampsia, the presence of IgM anti-phosphatidylserine/prothrombin could be associated with endothelial dysfunction, causing alteration of cardiovascular parameters.

Epidemiology of hyperkalemia in chronic kidney disease. / Epidemiología de la hiperpotasemia en la enfermedad renal crónica.

BACKGROUND: Hyperkalaemia is a significant electrolyte imbalance in chronic kidney disease (CKD). Renin-angiotensin-aldosterone system inhibitors (RAASi) have beneficial cardio-renal properties, although they can often cause hyperkalaemia. OBJECTIVE: To examine the prevalence of hyperkalaemia in CKD, identify factors associated with its appearance and the relationship between hyperkalaemia and mortality. PATIENTS AND METHODS: Retrospective observational study on patients with CKD in the period 1971-2017. The population was categorised into 3groups: Group 1, patients with CKD without renal replacement therapy; Group 2, patients on haemodialysis; and Group 3, patients on continuous ambulatory peritoneal dialysis. RESULTS: A total of 2,629 patients were evaluated. The prevalence observed in the different groups was: 9.6%, 16.4% and 10.6%, respectively. Risk factors related to the appearance of hyperkalaemia in the CKD group were glomerular filtration rate (GFR) (P<.001), plasma creatinine (P<.001), plasma sodium (P<.001), haemoglobin (P=.028), diastolic blood pressure (P=.012), intake of ACE inhibitors and/or angiotensin ii receptor blockers (P=.008), treatment with metformin (P<.001) and diabetes (P=.045). Treatment with RAASi significantly increased hyperkalaemia as GFR decreased, as well as in patients with diabetes or heart failure. CONCLUSIONS: Hyperkalaemia is a frequent metabolic alteration in CKD patients that increases in the presence of drugs with beneficial cardio-renal properties (RAASi), which means that patients often lose the benefit associated with these drugs. New, recently-appearing non-absorbable compounds, which bind to potassium in the gastrointestinal tract, enhancing faecal excretion and thus maintaining the cardio-renal benefit of the RAASi, could be relevant in the progress of patients with CKD.

New oral anticoagulants in patients with chronic kidney disease. / Nuevos anticoagulantes orales en pacientes con enfermedad renal crónica.

Patients with chronic kidney disease (CKD) develop bleeding and thrombotic tendencies, so the indication of anticoagulation at the onset of atrial fibrillation (AF) is complex. AF is the most common chronic cardiac arrhythmia, and thromboembolism and ischemic stroke in particular are major complications. In recent years, new oral anticoagulant drugs have been developed, and they have shown superiority over the classical AVK in preventing stroke, systemic embolism and bleeding risk, constituting an effective alternative to those resources.

Investigation of iron deficiency in patients with congestive heart failure: A medical practice that requires greater attention. / Estudio de la deficiencia de hierro en pacientes con insuficiencia cardiaca congestiva: una práctica clínica que precisa mayor atención.

INTRODUCTION: Iron deficiency in congestive heart failure (CHF), with or without concomitant anaemia, is associated with health-related quality of life, NYHA functional class, and exercise capacity. Prospective, randomised studies have demonstrated that correcting iron deficiency improves the quality of life and functional status of patients with CHF, including those who do not have anaemia. OBJECTIVE: The aim of this study was to analyse how frequently these iron parameters are tested and thus determine the extent to which this quality improvement tool has been implemented in patients admitted with CHF. METHODS: Retrospective observational study of patients from a university hospital diagnosed with CHF on admission between 01/01/2012 and 11/06/2013. RESULTS: Iron parameters were tested in 39% (324) of the 824 patients analysed. There was no significant difference in age between the patients whose iron was tested and those whose iron was not tested, but the difference in terms of gender was significant (P=.007). Glomerular filtration rate and haemoglobin, were significantly lower in the group of patients whose iron was tested (P<.001). The proportion of patients with anaemia, renal failure or both was significantly higher in the group of patients who had iron tests (P<.001). Of the 324 patients whose iron parameters were tested, 164 (51%) had iron deficiency. There were no differences between patients with and without iron deficiency in terms of age or gender. The iron parameters in both groups, ferritin and transferrin saturation index were significantly lower among the patients with iron deficiency (P<.001). The glomerular filtration rate values were significantly lower in patients with no iron deficiency (P<.001). Significant differences were also observed between those with and without iron deficiency in the proportion of patients with renal failure (79 vs. 66%, respectively, P=.013), but not in terms of haemoglobin concentration. CONCLUSION: Congestive heart failure is very frequently associated with anaemia, iron deficiency and renal failure. Despite the fact that correcting iron deficiency is known to improve symptoms, testing of iron parameters in patients admitted with CHF is not performed as often as it should be.