Mortality risk factors in community-dwelling, subjectively healthy, Swiss older adults: update after 8-years follow-up.

BACKGROUND: Worldwide population is ageing, but little is known regarding risk factors associated with increased mortality in subjectively healthy, community-dwelling older adults. We present the updated results of the longest follow-up carried out on Swiss pensioners and we provide results on potential risk factors associated with mortality before the onset of the COVID-19 pandemic. MATERIALS AND METHODS: Within the SENIORLAB study, we collected demographic data, anthropometric measures, medical history, and laboratory parameters of 1467 subjectively healthy, community-dwelling, Swiss adults aged ≥ 60 years over a median follow-up of 8.79 years. The variables considered in the multivariable Cox-proportional hazard model for mortality during follow-up were selected based on prior knowledge. Two separate models for males and females were calculated; moreover, we fitted the old model obtained in 2018 to the complete follow-up data to highlight differences and similarities. RESULTS: The population sample included 680 males and 787 females. Age of participants ranged between 60 and 99 years. We experienced 208 deaths throughout the entire follow-up period; no patients were lost at follow-up. The Cox-proportional hazard regression model included female gender, age, albumin levels, smoking status, hypertension, osteoporosis and history of cancer within predictors of mortality over the follow-up period. Consistent findings were obtained also after gender stratification. After fitting the old model, female gender, hypertension, and osteoporosis still showed statistically significant independent associations with all-cause mortality. CONCLUSIONS: Understanding the predictors of a healthy survival can improve the overall quality of life of the ageing population and simultaneously reduce their global economic burden. TRIAL REGISTRATION: The present study was registered in the International Standard Randomized Controlled Trial Number registry: https://www.isrctn.com/ISRCTN53778569 (registration date: 27/05/2015).

Oral glucose tolerance test does not affect degree of hemoglobin glycation as measured by routine assay.

BACKGROUND: Hemoglobin A1c (HbA1c) is an accurate index of fluctuation in glycemia over the 2-3 months prior to quantitative assessment. During this time, hemoglobin (Hb) slowly glycates until it shows the properties of advanced glycation end-products. Glycation kinetics is intensified by prolonged glucose exposure. In subjects undergoing oral glucose tolerance testing (OGTT), immediately after ingestion, glucose is ostensibly transported by the glucose transporter 1 (GLUT1) to erythrocyte corpuscular hemoglobin. The earliest significant measurable level of hemoglobin glycation associated with this transportation is still not clear. SUBJECTS AND METHODS: We attempted to explore the early impact of short-term glucose load on HbA1c levels, because it is now known that transmembrane GLUT1-mediated glucose transport occurs immediately. A total of 88 participants (46 patients and 42 clinically healthy controls) underwent fasting plasma glucose quantitation during an OGTT. HbA1c, revealed by a monoclonal anti-glycation epitope antibody and adiponectin, was quantitated before (T0) and 2 hours (T120) after 80 g glucose ingestion. RESULTS: Wilcoxon test revealed that the HbA1c values did not significantly vary (P=0.15) during the OGTT, whereas glucose concentration varied strongly between T0 and T120. DISCUSSION: It is well known that quantitative estimation of HbA1c is informative for clinical care, independently of glucose level. The molecular mechanisms and dynamics by which glucose enters/exits red blood cells are incompletely known and may differ between individuals. We here show, for the first time, that HbA1c levels do not significantly increase during OGTT, supporting the view that non-enzymatic glycation of hemoglobin occurs slowly and that glycation during the 2 hours of an OGTT is insignificant.

A consideration of convalescent plasma and plasma derivatives in the care of Severely-ill patients with COVID-19.

The pathogenesis and immunopathological damage of severe forms of COVID-19 resemble acute autoimmune disease sparked by SARS-CoV-2, including an early systemic overproduction of proinflammatory cytokines. Such immunopathological features provide a rationale for the use of passive immunotherapy with convalescent plasma as a source of neutralizing anti-viral antibodies and of anti-inflammatory plasma components. While convalescent plasma therapy is now being evaluated in prospective clinical trials, we further consider the therapeutic potential of human hyper immune globulins, and of heterologous, engineered and monoclonal neutralizing antibodies as anti-viral agents to treat COVID-19. Good medical practice procedures are still needed and is why we also discuss the potential use of polyclonal polyspecific immunoglobulins (IVIG), a therapeutic plasma derivative, with potent anti-inflammatory activity, in severe forms of Covid-19.

Reference Intervals for Platelet Counts in the Elderly: Results from the Prospective SENIORLAB Study.

Currently, age- and sex-independent reference limits (RLs) are frequently used to interpret platelet counts in seniors. We aimed to define and validate reference intervals (RIs) for platelet counts within the framework of the prospective SENIORLAB study. Subjectively healthy Swiss individuals aged 60 years and older were prospectively included and followed for morbidity and mortality. Participants who had circumstances known to affect platelet counts were excluded. The obtained RIs were validated with indirect statistical methods. Frequencies of abnormal platelet counts in a population-based setting, including 41.5% of the entire age-specific population of the Principality of Liechtenstein, were compared by using age- and sex-independent RIs and the RLs obtained in the present study. For males (n = 542), 95% RIs for platelet counts were defined as follows: 150-300 × 109/L (60-69 years); 130-300 × 109/L (70-79 years); and 120-300 × 109/L (80 years and above). For females (n = 661), the consolidated age-independent 95% RI was 165-355 × 109/L. These RI values were validated by indirect RI determination of 51,687 (30,392 female/21,295 male) patients of the same age. Age- and sex-independent RIs exhibited imbalanced frequencies of abnormal platelet counts between the two sexes, which were corrected by introducing age- and sex-specific RLs. In conclusion, females have higher platelet counts than males. Whereas the upper RL for males remains constant, the lower RL decreases with age. We propose to abandon the practice of employing sex- and age-independent RL for platelet counts in the elderly.

Glycaemic patterns in healthy elderly individuals and in those with impaired glucose metabolism - exploring the relationship with nonglycaemic variables.

OBJECTIVE: The SENIORLABOR study data were explored (i) to examine the evolution during senescence of the differences between measured glycated haemoglobin (HbA1c) values and the values predicted by using regression to extrapolate from measured fructosamine levels; (ii) to scrutinise the relationship between the glycation gap and insulin resistance using a homeostasis model assessment, and between the glycation gap and a low-grade inflammation marker (C-reactive protein serum concentration); and (iii) to investigate the glycation gap ranges in relation to triglyceride levels and kidney function. SUBJECTS AND METHODS: A total of 1432 Swiss individuals aged >60 years and classified as healthy (547), prediabetic (701) or diabetic (184) based on their fasting plasma glucose and HbA1c values were included in the study. The glycation gap was evaluated and assigned to one of four categories: <−0.5; −0.5 to <0.0; 0.0 to ≤0.5; >0.5. RESULTS: In healthy and prediabetic participants, the homeostasis model assessment for estimation of insulin resistance (p <0.01), high-sensitivity C-reactive protein (p <0.001) and triglyceride (p = 0.02) values tended to increase with increasing glycation gap category and were highest in the glycation gap category >0.5. Homeostasis model assessment for estimation of insulin resistance, high-sensitivity C-reactive protein and triglyceride levels tended to increase with increasing glycation gap category and were highest in the glycation gap category >0.5. Significant differences (p <0.01) between glycation gap categories were seen among different high-sensitivity C-reactive protein concentration groups. Interestingly, in diabetic participants, homeostasis model assessment for estimation of insulin resistance values, triglyceride concentrations and estimation of glomerular filtration values all decreased with decreasing glycation gap category. In the group of participants with a glycation gap >0.5, high-sensitivity C-reactive protein values tended to increase with increasing glycation gap, whereas for participants with type 2 diabetes and in the glycation gap group >0.5, high-sensitivity C-reactive protein levels tended to decrease as the glycation gap increased. The percentage of participants with type 2 diabetes mellitus increased from 2% in the glycation gap category <−0.5 to 76% in the glycation gap category >0.5. In contrast, the percentage of healthy participants fell from 85% to 7%. CONCLUSION: This is the first time that a direct comparison of healthy, prediabetic and diabetic participants, all assessed under identical conditions and using identical methodology, has clearly demonstrated a different glycation gap pattern. Thus, we contribute evidence that the glycation gap might be of interest in the care of diabetic patients and their prophylaxis, while acknowledging that more studies are needed to confirm our findings. (Trial registration number ISRCTN53778569).

Osteoporosis, diabetes, and hypertension are major risk factors for mortality in older adults: an intermediate report on a prospective survey of 1467 community-dwelling elderly healthy pensioners in Switzerland.

BACKGROUND: Osteoporosis is an important morbidity factor for ageing populations in developed countries. However, compared to the amount of information available on diabetes and cardiovascular disease, little is known about the direct impact of osteoporosis on general mortality in older age. METHODS: We obtained data from a prospective population-based cohort of pensioners from the SENIORLAB study who were subjectively healthy. The inclusion criteria were an age of at least 60 years and Swiss residence. We assessed and analysed clinical measures, voluntary reports, and laboratory values. RESULTS: In total, 1467 subjects were included in the cohort. The mean follow-up time was 3.68 years (95% confidence interval, 3.64-3.71). The ages of the included participants ranged from 60 to 99 years. At follow-up, there were 1401 survivors, and 66 participants had died. According to the multivariate analysis (Cox regression), osteoporosis was the most important risk factor for all-cause mortality (hazard ratio, 4.46; 95% confidence interval, 1.82-10.91), followed by diabetes (hazard ratio, 2.17; 95% confidence interval, 1.04-4.52) and hypertension (hazard ratio, 1.81; 95% confidence interval, 1.09-3.03). CONCLUSIONS: Osteoporosis is a major risk factor for all-cause mortality in a subjectively healthy senior population, followed by type 2 diabetes mellitus and hypertension. Osteoporosis should be more actively diagnosed in healthy pensioners before they develop osteoporosis-associated health incidents. TRIAL REGISTRATION: The present study was registered in the International Standard Randomized Controlled Trial Number registry: ISRCTN53778569 .

Complement systems C4, C3 and CH50 not subject to a circadian rhythm.

BACKGROUND: The circadian fluctuations in the blood levels of selected components of the complement system are ill-defined. Some authors found nadir serum levels of C4 and C3 components, together with C3a at nighttime, while others reported insomnia when pro-inflammatory components exhibited increased serum levels. In this study, we quantitatively estimate the morning and evening daytime serum levels of CH50, C4, C3, put into context with C-reactive protein (CRP), cortisol, parathyroid hormone (PTH) and 25(OH)vitamin D at 07:00 A.M. and at 07:00 P.M. METHODS: Seven healthy adult women and 11 men who were voluntary participants agreed to a fasting venipuncture in the morning after having normally eaten through the day and in the evening. The C4 and C3 serum levels were measured on a Cobas (Roche Diagnostics, Switzerland) modular analyzer, CH50 was estimated using the COMPL300 enzyme-linked immunosorbent assay (ELISA) of Wieslab (Malmö, Sweden). CRP, 25(OH)vitamin D, PTH and cortisol concentrations were assessed with electro-chemiluminescence immunoassay (ECLIA) on the Roche Cobas 6000 platform; IgG was measured using nephelometry (Siemens, Germany). RESULTS: With the exception of higher PTH levels in the evening [3.12-5.46, 95% confidence interval (CI)] compared to the morning (2.93-4.65, 95% CI), the mean and median values of C4, C3, CH50 as well as CRP, PTH and 25(OH)vitamin D fell within the established reference intervals. Cortisol levels were measured as an internal positive control for diurnal fluctuations (morning: 294-522 nmol/L, 95% CI; evening: 106-136 nmol/L, 95% CI). CONCLUSIONS: The concentrations of the assessed complement components C4 and C3 as well as CH50 surrogate assay did not yield significantly different values between early morning and evening. This does not exclude their participation in the circadian metabolome; this pilot study with healthy participants suggests that patients with an autoimmune disease in remission can give their blood samples independently during daytime with or without fasting.

The cystatin C/creatinine ratio, a marker of glomerular filtration quality: associated factors, reference intervals, and prediction of morbidity and mortality in healthy seniors.

The ratio of cystatin C (cysC) to creatinine (crea) is regarded as a marker of glomerular filtration quality associated with cardiovascular morbidities. We sought to determine reference intervals for serum cysC-crea ratio in seniors. Furthermore, we sought to determine whether other low-molecular weight molecules exhibit a similar behavior in individuals with altered glomerular filtration quality. Finally, we investigated associations with adverse outcomes. A total of 1382 subjectively healthy Swiss volunteers aged 60 years or older were enrolled in the study. Reference intervals were calculated according to Clinical & Laboratory Standards Institute (CLSI) guideline EP28-A3c. After a baseline exam, a 4-year follow-up survey recorded information about overall morbidity and mortality. The cysC-crea ratio (mean 0.0124 ± 0.0026 mg/µmol) was significantly higher in women and increased progressively with age. Other associated factors were hemoglobin A1c, mean arterial pressure, and C-reactive protein (P < 0.05 for all). Participants exhibiting shrunken pore syndrome had significantly higher ratios of 3.5-66.5 kDa molecules (brain natriuretic peptide, parathyroid hormone, ß2-microglobulin, cystatin C, retinol-binding protein, thyroid-stimulating hormone, α1-acid glycoprotein, lipase, amylase, prealbumin, and albumin) and creatinine. There was no such difference in the ratios of very low-molecular weight molecules (urea, uric acid) to creatinine or in the ratios of molecules larger than 66.5 kDa (transferrin, haptoglobin) to creatinine. The cysC-crea ratio was significantly predictive of mortality and subjective overall morbidity at follow-up in logistic regression models adjusting for several factors. The cysC-crea ratio exhibits age- and sex-specific reference intervals in seniors. In conclusion, the cysC-crea ratio may indicate the relative retention of biologically active low-molecular weight compounds and can independently predict the risk for overall mortality and morbidity in the elderly.

Incidence of preeclampsia in pregnant Swiss women.

QUESTION UNDER STUDY: The epidemiology of preeclampsia in Switzerland is known only from a retrospective registry study. This analysis aimed to prospectively determine the incidence of preeclampsia in a cohort of pregnant women in Switzerland. METHODS: Pregnant women presenting at gestational week 11-14 at their obstetrician's office were consecutively included and prospectively followed-up until the end of pregnancy. Ultrasound characteristics, blood pressure measurements, body mass index, and personal history were recorded. Duration of pregnancy, occurrence of preeclampsia, birth weight and Apgar scores were recorded as outcomes. RESULTS: There were 1,300 pregnancies with follow-up available for analysis. Median age was 30 years (interquartile range [IQR] 27-33), median body mass index (BMI) 23.3 kg/m² (IQR 21.2-26.1), median systolic blood pressure 117 mm Hg (IQR 109-126) and median diastolic blood pressure 70 mm Hg (IQR 64-77). A total of 30 women developed preeclampsia, corresponding to an incidence of 2.31% (95% confidence interval [CI] 1.62%-3.28%). Of the women with preeclampsia, 6.66% (95% CI 2.04%-21.42%) had early-onset preeclampsia, 13.33% (95% CI 5.45%-29.83%) progressed to eclampsia, whereas 10% (95% CI 3.63%-28.75%) developed HELLP syndrome (haemolysis, elevated liver enzymes, low platelet count). Nulliparity and prior history of preeclampsia were more frequently seen in pregnancies with preeclampsia than in pregnancies without preeclampsia. BMI, as well as systolic and diastolic blood pressure were higher in pregnancies subsequently developing preeclampsia. CONCLUSION: The incidence of preeclampsia in Switzerland is in line with frequencies observed elsewhere in the world. Extrapolation to a national level indicates that about 1,911 (range 1,340-2,713) preeclampsia cases per year can be expected to occur in Switzerland.

The aging human recipient of transfusion products.

In this review the different mechanisms of aging and frailty such as DNA defects due to impaired DNA repair, inflammatory processes, disturbances of oxidative phosphorylation are discussed together with mechanisms of cell repair. Components of blood plasma, such as the growth-differentiation protein GDF11, were shown to enhance neurogenesis and to improve the vasculature in the animal cortex and to rejuvenate muscle tissue. Advances in laboratory assays allow to identify plasma proteins that may affect tissue regeneration. This new knowledge from animal research might affect transfusion practice in geriatric patients in the future. Provided it can be translated and confirmed in human research, blood products might no longer be considered only as oxygen carriers or drugs to improve hemostasis. In the present time blood transfusion (RBCs, plasma or platelets) should be directed by differentiated guidelines considering not only cut-off values of hemoglobin, platelet count or coagulation but also old age-specific biologic variation, comorbidities and the clinical context e.g. of bleeding.

The serum uromodulin level is associated with kidney function.

BACKGROUND: In chronic kidney diseases of various etiologies, the urinary excretion of uromodulin is usually decreased in parallel with the glomerular filtration rate. This study aimed to investigate whether serum uromodulin is associated with kidney function. METHODS: Within the framework of the Seniorlabor study, a subset of subjectively healthy individuals 60 years of age and older were included in the study. Serum uromodulin was measured with ELISA. The relationship between serum uromodulin and different stages of kidney function (i.e., cystatin C-based 2012-CKD-EPI eGFRCysC>90 mL/min/1.73 m2, 60-89 mL/min/1.73 m2, 45-59 mL/min/1.73 m2, and <45 mL/min/1.73 m2) was investigated. Furthermore, the relationship between serum uromodulin and other markers of kidney function (i.e., creatinine, cystatin C, and urea) was assessed. RESULTS: In total, 289 participants (140 males/149 females; mean age 71±7 years) were included in the study. There were significant differences in serum uromodulin among the four groups according to different kidney function stages (p<0.001). Serum uromodulin displayed inverse relationships with creatinine (r=-0.39), cystatin C (r=-0.42), and urea (r=-0.30) and, correspondingly, a positive relationship with eGFRCysC (r=0.38, p<0.001 for all). These associations remained intact when fitting a regression model that incorporated age, gender, body mass index, and current smoking status as covariates. CONCLUSIONS: Serum uromodulin behaves in a manner opposite that of the different conventional renal retention markers by displaying lower concentrations with decreasing kidney function. As uromodulin is produced by the cells of the thick ascending limb of the loop of Henle, lower uromodulin serum levels may reflect a reduction in number or function of these cells in chronic kidney disease.

Chronobiology and circadian rhythms establish a connection to diagnosis.

Circadian rhythms are synchronized by the light/dark (L/D) cycle over the 24-h day. A suprachiasmatic nucleus in the hypothalamus governs time keeping based on melanopsin messages from the retina in the eyes and transduces regulatory signals to tissues through an array of hormonal, metabolic and neural outputs. Currently, vague impressions on circadian regulation in health and disease are replaced by scientific facts: in addition to L/D cyling, oscillation is maintained by genetic (Clock, Bmal1, Csnk1, CHRONO, Cry, Per) programs, autonomous feedback loops, including melatonin activities, aerobic glycolysis intensity and lipid signalling, among others. Such a multifaceted influential system on circadian rhythm is bound to be fragile and genomic clock acitvities can become disrupted by epigenetic modifications or such environmental factors as mistimed sleep and feeding schedules albeit leaving the centrally driven melatonin-dependent pacemakter more or less unaffected.

Anti-red blood cell antibodies, free light chains, and antiphospholipid antibodies in intravenous immunoglobulin preparations.

BACKGROUND: Anti-red blood cell antibodies, free light chains (FLC) and prothrombotic proteins (PTP) may co-elute with intact immunoglobulin (IgG), and may be the cause of adverse reactions to intravenous immunoglobulin preparations (IVIG). OBJECTIVES: To investigate the presence of residual amounts of these components in IVIG and their effects on ABO blood group agglutination. METHODS: Iso-agglutinin anti-A and anti-B activity was determined with a direct hemagglutination assay of red blood cell (RBC) suspensions from 1% of 46 blood donors together with the serial dilutions of five IVIG (IV1, IV2, IV3, IV4, IV5). Anti-A1 monoclonal antibody was used to confirm reactivity with the A1-reference RBC. The selected IVIG were diluted to a final concentration of 25 mg/ml in 0.15 M NaCI and 0.01 M phosphate-buffered saline, pH 7.4, with or without a further twofold dilution in a low ionic strength solution. RESULTS: A variation up to fivefold in the titer strength of anti-A/B activity was observed between the IVIG preparations. A2-type RBC required higher IVIG inputs when tested in 0.15 M NaCl. The differences in FLC kappa and lambda concentrations were as high as > 400 mg/L among the various IVIG. Only IV1 had a significantly high level of antiphospholipid IgG antibodies (18 U/ml). We demonstrated the presence of anti-RBC antibodies, FLC and PTP in IVIG preparations. CONCLUSIONS: Our findings provide clear evidence that IVIG may harbor pathophysiological substrates with a potential risk for adverse effects such as iatrogenic hemolysis, FLC-associated disorders, and thromboembolism.

Serum concentrations of 25-hydroxyvitamin D and immunoglobulins in an older Swiss cohort: results of the Senior Labor Study.

BACKGROUND: Vitamin D and the components of humoral immunity play important roles in human health. Older people have lower 25-hydroxyvitamin D (25(OH)D) serum levels than younger adults. We aimed to determine the levels of 25(OH)D serum concentrations in healthy senior citizens and to study their relationship to the levels of components of humoral immunity. METHODS: A total of 1,470 healthy Swiss men and women, 60 years or older, were recruited for this study. A total of 179 subjects dropped out of the study because of elevated serum concentrations of C-reactive protein. Fasting blood sera were analyzed for 25(OH)D with the high-performance liquid chromatography (HPLC) and for parathyroid hormone (PTH), immunoglobulins and complement C4 and C3 concentrations with immunoassays. The percentage of participants in each of the four 25(OH)D deficiency groups--severely deficient (<10 ng/ml), deficient (10 to 20), insufficient (21 to 29 ng/ml) and normal (>=30 ng/ml)--were statistically compared. The relationship of the major components of the humoral system and age with 25(OH)D levels was also assessed. RESULTS: About 66% of the subjects had insufficient levels of 25(OH)D. Normal levels of 25(OH)D were found in 26.1% of the subjects of which 21% were males and 30.5% were females (total study population). Severely deficient levels of 25(OH)D were found in 7.98% of the total study population. Low levels of 25(OH)D were positively associated with IgG2 (P = 0.01) and with C4 (P = 0.02), yet were inversely related to levels of IgG1 and IgA (P < 0.05) and C3 (P = 0.01). Serum levels of total IgA, IgG, IgG2 and IgG4 peaked together with 25(OH)D during late summer. CONCLUSIONS: Approximately two-thirds of the healthy, older Swiss population presented with Vitamin D insufficiency. The incremental shift in IgA and C3 levels might not necessarily reflect a deranged humoral immune defense; however, given the high prevalence of vitamin D deficiency, the importance of this condition in humoral immunity will be worth looking at more closely. This study supports the role of vitamin D in the competent immune system.

Factors other than the glomerular filtration rate that determine the serum beta-2-microglobulin level.

BACKGROUND: ß2-microglobulin has been increasingly investigated as a diagnostic marker of kidney function and a prognostic marker of adverse outcomes. To date, non-renal determinants of ß2-microglobulin levels have not been well described. Non-renal determinants are important for the interpretation and appraisal of the diagnostic and prognostic value of any endogenous kidney function marker. METHODS: This cross-sectional analysis was performed within the framework of the www.seniorlabor.ch study, which includes subjectively healthy individuals aged ≥ 60 years. Factors known or suspected to have a non-renal association with kidney function markers were investigated for a non-renal association with serum ß2-microglobulin. As a marker of kidney function, the Berlin Initiative Study equation 2 for the estimation of the estimated glomerular filtration rate (eGFR(BIS2)) in the elderly was employed. RESULTS: A total of 1302 participants (714 females and 588 males) were enrolled in the study. The use of a multivariate regression model adjusting for age, gender and kidney function (eGFR(BIS2)) revealed age, male gender, and C-reactive protein level to be positively associated with ß2-microglobulin levels. In addition, there was an inverse non-renal relationship between systolic blood pressure, total cholesterol and current smoking status. No association with markers of diabetes mellitus, body stature, nutritional risk, thyroid function or calcium and phosphate levels was observed. CONCLUSIONS: Serum ß2-microglobulin levels in elderly subjects are related to several non-renal factors. These non-renal factors are not congruent to those known from other markers (i.e. cystatin C and creatinine) and remind of classical cardiovascular risk factors.

Selected topics of the 4th International Cooperative Study Group meeting on immune thrombocytopenia revisited.

The Intercontinental Cooperative immune thrombocytopenia (ITP) Study Group (ICIS) held its 4th Expert Meeting in September 2012 in Montreux, Switzerland. The program reunited researchers and clinicians from all over the globe and was organized with lectures and seminars for real-time exchange of latest information. Platelets target victims of autoimmune disease on their own, participating under physiological conditions in the immune network; these small cells are more immunologically savvy than previously thought. Currently, researchers focus their attention on regulatory T and regulatory B cells, ie, cells that might have a decisive impact on how ITP spontaneously resolves or evolves into chronic disease. Diagnostic criteria and prognosis are increasingly benefiting from molecular biological tests, and therapy has evolved with the availability of biosimilar agents and recombinant hormones or blockers of their receptors.

Benefits and risks of IgA in immunoglobulin preparations.

The case of Immunoglobulin A (IgA) in transfusion medicine is unsettled: on one hand IgA is an important component of adaptive immunity and its deficiency may cause disease, on the other its presence in blood products might induce, in rare instances, allergy-like symptoms if not anaphylaxis. The practice with i.v. immunoglobulins currently changes as up to 10% concentrated preparations are given at fast rates hence even trace amounts of IgA contained in these IgG preparations can cause unexpected (side-) effects. Fortunately, the spectrum of sensitive IgA assays, along with anti-IgA screening assays now permits laboratories to narrow down IgA-dependent transfusion reactions to the real cases, in which IgA was the decisive trigger of anaphylaxis, proven or not by the presence of anti-IgA of the IgG or even IgE class. Tolerance to allogenic IgA has recently been reported. The known association of HLA with IgA deficiency (IgAD) has now been completed with an association to the nonsynonymous variant in IFHI1, allowing physicians to more precisely spot recipients at risk for an IgA-dependent transfusion reaction. Our review, along with our own experience here in Switzerland, allows us to conclude that IgA is a beneficial antibody rather than an allergen to be placed at the end of the list of non-infectious transfusion complications such as TRALI, febrile non-hemolytic reactions, purpura or volume overload.