Increased Serum IgA Levels Research Articles

Effects of silybin supplementation on growth performance, serum indexes and liver transcriptome of Peking ducks.

As an emerging feed additive extracted from the traditional herb milk thistle, silybin has few applications and studies in Peking ducks. The aim of this study was to explore the practical significance of silymarin application in Peking ducks and to provide more theoretical support for the application of silymarin in livestock and poultry production. A total of 156 1-day-old healthy Peking ducks were randomly divided into four groups and supplemented with 0 mg/kg (control group), 400 mg/kg (S400), 800 mg/kg (S800) and 1,600 mg/kg (S1600) of silybin in the diets at day 14, to investigate the effects of silymarin on the growth, serum indexes and liver transcriptome of Peking ducks. The whole experiment lasted until day 42, and the sample collection was scheduled to take place in the morning. A substantial inprovement in average daily gain (ADG) and a decrease in feed conversion ratio (FCR) occurred in the S1600 group on days 14-28 compared to the control group (p < 0.05). The FCRs of other additive groups in the same period showed the same results. Supplementation of diets with silybin significantly increased serum IgA levels and when 1,600 mg/kg of silybin was given, levels of TNF-α and IL-6 were also significantly decreased (p < 0.05). In addition, we observed that the S1600 group had a significantly lower (p < 0.05) glutamine transaminase and an increased (p < 0.05) T-SOD level in the S400 group (p < 0.05). Liver transcriptome sequencing showed that 71 and 258 differentially expressed genes (DEGs) were identified in the S400 and S1600 groups, respectively, compared with the control group. DEGs related to cell composition and function, antigen processing and presentation were up-regulated, while DEGs related to insulin resistance and JAK-STAT were down-regulated. Conclusively, silybin can be used as a feed additive to improve the growth performance and health status of Peking ducks.

Overexpression of Transmembrane TNF Drives Development of Ectopic Lymphoid Structures in the Bone Marrow and B Cell Lineage Alterations in Experimental Spondyloarthritis.

TNF is important in immune-mediated inflammatory diseases, including spondyloarthritis (SpA). Transgenic (tg) mice overexpressing transmembrane TNF (tmTNF) develop features resembling human SpA. Furthermore, both tmTNF tg mice and SpA patients develop ectopic lymphoid aggregates, but it is unclear whether these contribute to pathology. Therefore, we characterized the lymphoid aggregates in detail and studied potential alterations in the B and T cell lineage in tmTNF tg mice. Lymphoid aggregates developed in bone marrow (BM) of vertebrae and near the ankle joints prior to the first SpA features and displayed characteristics of ectopic lymphoid structures (ELS) including presence of B cells, T cells, germinal centers, and high endothelial venules. Detailed flow cytometric analyses demonstrated more germinal center B cells with increased CD80 and CD86 expression, along with significantly more T follicular helper, T follicular regulatory, and T regulatory cells in tmTNF tg BM compared with non-tg controls. Furthermore, tmTNF tg mice exhibited increased IgA serum levels and significantly more IgA+ plasma cells in the BM, whereas IgA+ plasma cells in the gut were not significantly increased. In tmTNF tg × TNF-RI-/- mice, ELS were absent, consistent with reduced disease symptoms, whereas in tmTNF tg × TNF-RII-/- mice, ELS and clinical symptoms were still present. Collectively, these data show that tmTNF overexpression in mice results in osteitis and ELS formation in BM, which may account for the increased serum IgA levels that are also observed in human SpA. These effects are mainly dependent on TNF-RI signaling and may underlie important aspects of SpA pathology.

Evaluation of Oral Administration of Lactobacillus plantarum CAM6 Strain as an Alternative to Antibiotics in Weaned Pigs.

Simple SummaryCurrently, due to intensive production, pigs are weaned early, which generates stress due to separation from the sow, metabolic disorders, and decreased productive performance. Thus, sub-therapeutic antibiotics have been used to alleviate these detrimental effects; however, it has been shown that these practices create microbial resistance and cross-resistance to other microorganisms. Although the European Union banned antibiotic growth promoters (AGP), many countries in the world still use them widely. In the present study, oral administration of Lactobacillus plantarum CAM6 in weaned pigs improved productive performance from the second experimental week and increased total serum levels of IgA without causing adverse effects on health indicators and acid-base balance. These results suggest this probiotic bacterium can be used as an alternative to antibiotics in weaned pigs.The objective was to evaluate the effect of oral administration of Lactobacillus plantarum CAM6 strain as an alternative to antibiotics in weaned pigs on productive parameters, blood biochemical profile, and IgA serum levels. Thirty-six 21-day-old weaned piglets were randomly assigned to three groups with three replicates of four piglets each. Treatments consisted of a basal diet (BD; T0) without probiotics or antibiotics; BD + antibiotics and the same basal diet used in T0 plus oral administration of 5 mL × 109 CFU/mL of L. plantarum CAM-6 (T2). During the study (21 to 49 days of age) T2 obtained a similar live weight, weight gain, and feed conversion ratio when compared to the T1. Both treatments were better in these variables compared to T0 (p ≤ 0.05). Furthermore, T2 increased serum IgA levels (p ≤ 0.05). Additionally, hematological parameters and acid-base balance remained similar in all groups. However, significant reductions in the mean corpuscular hemoglobin concentration, platelets, and metabolic hydrogen ions were observed in T1 (p ≤ 0.05). The results of this study suggest that supplementation with L. plantarum CAM6 can be an alternative to antibiotics. Studies to evaluate its efficacy under commercial conditions and water administration require further evaluation.

Henoch-Schönlein purpura in northern Spain: clinical spectrum of the disease in 417 patients from a single center.

The severity of clinical features and the outcomes in previous series of patients reported with Henoch-Schönlein purpura (HSP) vary greatly, probably due to selection bias. To establish the actual clinical spectrum of HSP in all age groups using an unselected and wide series of patients diagnosed at a single center, we performed a retrospective review of 417 patients classified as having HSP according to the criteria proposed by Michel et al. Of 417 patients, 240 were male and 177 female, with a median age at the time of disease diagnosis of 7.5 years (interquartile range [IQR], 5.3–20.1 yr). Three-quarters of the patients were children or young people aged 20 years or younger (n = 315), and one-quarter were adults (n = 102). The most frequent precipitating events were a previous infection (38%), usually an upper respiratory tract infection, and/or drug intake (18.5%) shortly before the onset of the vasculitis. At disease onset the most common manifestations were skin lesions (55.9%), nephropathy (24%), gastrointestinal involvement (13.7%), joint symptoms (9.1%), and fever (6.2%). Cutaneous involvement occurring in all patients, mainly purpuric skin lesion, was the most common manifestation when the vasculitis was fully established, followed by gastrointestinal (64.5%), joint (63.1%), and renal involvement (41.2%). The main laboratory findings were leukocytosis (36.7%), anemia (8.9%), and increased serum IgA levels (31.7%). The most frequent therapies used were corticosteroids (35%), nonsteroidal antiinflammatory drugs (14%), and cytotoxic agents (5%). After a median follow-up of 12 months (IQR, 2–38 mo), complete recovery was observed in most cases (n = 346; 83.2%), while persistent, usually mild, nephropathy was observed in only 32 (7.7%) cases. Relapses were observed in almost a third of patients (n = 133; 31.9%).In conclusion, although HSP is a typical vasculitis affecting children and young people, it is not uncommon in adults. The prognosis is favorable in most cases, depending largely on renal involvement.

FRI0102 The significance of serum iga in rheumatoid arthritis in the era of biologic therapy

BackgroundIt is reported that patients with rheumatoid arthritis (RA) have increased IgA concentrations that are related to disease activity1). However, since the introduction of biologic therapy, few studies have been...

Serum levels of immunoglobulins (IgG, IgA, IgM) in Antarctic summer expeditioners and their relationship with seasickness

The Antarctic continent is full of environmental extremes like isolation, cold, UV exposure, and blizzards etc. The present study was conducted to analyze the effect of ship borne journey and the impact of Antarctic harsh environment on serum immunoglobulin (IgG, IgM, IgA) levels and their relationship with seasickness in Indian expeditioners. It was observed that one month onboard ship journey induced an increase in serum IgA levels and decrease in IgG levels while after being one month off board at the Indian research station Maitri, decreased levels of IgG and increased levels of IgA were found. IgM levels were not altered in comparison to the base line control. Moreover, serum IgG level showed a positive correlation while IgA level showed a negative correlation with seasickness. The stimulation of human peripheral blood mononuclear cells (PBMCs) with serum of expeditioner at different places showed that IgA at lower dose induces the release of pro-inflammatory IL-1β, and IL-6 cytokines from PBMCs while higher dose of IgA decreases proinflammatory cytokine production. The release of anti-inflammatory cytokines TGF-β1 and IL-10 was not significantly altered. Thus, the present study concluded that ship borne journey and Antarctic environment lead to increased serum IgA levels while decreased IgG levels. It also suggests that serum IgA level could be a possible biomarker for environmental stress.

IgA Nephropathy in Cirrhosis; Incidence, Pathogenesis, and Clinical Significance: Literature Review

Purpose: Increased serum IgA levels are found in the vast majority of cirrhotic patients with resulting glomerular IgA deposition in many of these patients. Many theories are available to explain this association but the clinical significance behind this glomerular deposition remains a mystery. The aim of this review is to evaluate the incidence, pathogenesis, and clinical significance of glomerular IgA deposition in cirrhosis. Methods: An extensive literature review was conducted of studies about the dysregulation of IgA immune complex (IC) clearance in cirrhotic patients and their deposition in the glomeruli with a focus on the clinical significance behind that. Results: Numerous studies described renal histology in cirrhosis (as revealed by biopsies at the time of liver transplantation or autopsies post-mortem) in addition to describing the kidney function by measuring serum creatinine whether at the time of the biopsy/autopsy or in the preceding few months. These studies reported glomerular IgA deposition rate of 50-90% making cirrhosis by far the most common cause of secondary IgA nephropathy (IgAN). There are two most accepted theories behind this high rate of glomerular deposition. The clearance theory focuses on the role of the liver in clearing IgA IC through the asialoglycoprotein receptor on the hepatocytes and the Fc receptor on Kupffer cells. The second theory in turn focuses more about the portacaval shunting that occurs with portal hypertension which shunts these IC and thus escaping the liver. Now, the clinical importance of secondary IgAN in cirrhotics remains the biggest dilemma. All studies reviewed agree that most patients are asymptomatic (>90%). If the disease becomes clinically active, hematuria is the most common presenting sign/symptom (exactly as primary IgAN) while nephrotic range proteinuria is much less common. Most studies also agree that the disease remains stable over many years with very few patients reported to progress to end stage renal disease (ESRD) over years. Nonetheless, most studies remark that the activity of urine sediments predicts glomerular and mesangial cell injury. Conclusion: Second IgAN is the most common histological renal finding observed in cirrhotic patients although this seems to represent a stable histologic diagnosis that can rarely (<10% of cases) progress to apparent clinically significant renal disease and much less likely to progress to ESRD over many years.

Genetic potential for an acute inflammatory response in IgA glomerulonephritis in mice

Mice selected on the basis of an acute inflammatory response (AIR) can provide information about the immunopathological mechanisms of glomerulonephritis. We studied the differences between mice selected for a maximal AIR (AIRmax that attract more polymorphonuclear cells to the site of injury) or a minimal AIR (AIRmin that attract more mononuclear cells) in an experimental model of IgA nephropathy in order to investigate the effect of genetic background on glomerular disease progression and the participation of the monocyte chemoattractant protein-1 (MCP-1) chemokine. IgA nephropathy was induced by intraperitoneal ovalbumin injection and bile duct ligation in AIRmax and AIRmin mice. Histological changes, urinary protein/creatinine ratio, serum IgA levels, immunofluorescence for IgA, IgG and complement C3 fraction, immunohistochemistry for macrophages and MCP-1, and MCP-1 levels in macerated kidney were determined. Mesangial IgA deposition was seen only in AIRmin mice, which presented more renal lesions. Increased serum IgA levels (1.5 +/- 0.4 vs 0.3 +/- 0.1 mg/mL, P < 0.001), high glomerular MCP-1 expression and decreased monocyte/macrophage infiltration in the interstitial area (0.3 +/- 0.3 vs 1.1 +/- 0.9 macrophages/field, P < 0.05) were detected in AIRmin mice compared to AIRmax mice. No glomerular monocyte/macrophage infiltration was detected in either strain. In spite of the absence of IgA deposition, AIRmax mice presented discrete or absent mesangial proliferation. The study showed that there are differences between mice selected for AIRmax and AIRmin with respect to serum IgA levels, histological damage and MCP-1 chemokine production after ovalbumin injection in combination with bile duct ligation.

Expression of porcine epidermal growth factor in Pichia pastoris and its biology activity in early-weaned piglets

Early-weaned piglets often have abnormalities in intestinal morphology and function. Epidermal growth factor (EGF) is critical in the development and in the repair of the gastrointestinal tract in pigs. This study investigated the effects of dietary EGF supplementation on growth performance and small intestinal morphology of early-weaned piglets. The functional domain of porcine EGF (pEGF) was cloned after RT-PCR amplification. The recombinant protein was expression by the Pichia pastoris expression system and the construct pPIC9K–pEGF was transformed into host GS115. The secretary recombinant protein in the supernatants was analyzed by SDS-PAGE. The gel indicated that the extra band at 6 kDa in the transformant, which corresponds to the standard hEGF, were both reactive to anti-pEGF antibody by Western blotting. The expression level of pEGF in the culture supernatant was 870 μg/mL. An animal feeding test was conducted to identify the effects of pEGF supplementation on growth performance and the development of digestive tracts of 14-day weaned piglets. The dietary treatment was a corn–soybean meal basal diet either with or without 1.5 mg/kg recombinant pEGF from the transformant fermentative supernatant. Dietary treatments enhanced the daily gain during 0–7 days postweaning ( p < 0.05), but did not affect the performance throughout the entire test period. Dietary supplemental pEGF significantly increased serum IgA levels on day 18 postweaning, and increased the mucosa IgA levels and crypt depth at jejunum on day 28 postweaning ( p < 0.05). The experimental results showed that the recombinant pEGF could be secreted by P. pastoris. The trophic effects of pEGF on growth performance, immune response, and small intestine development were determined by feeding recombinant pEGF to early-weaned piglets.

IgA Nephropathy

IgA Nephropathy

Erkrankungsstadium und IgA-anti-Fab/F(ab')2-Autoantikörperaktivität im Serum von Patienten mit malignen Kopf-Hals-Tumoren*

Patients with malignant tumors of the head and neck often show immune defects. Increased serum IgA levels have been reported in these groups of patients. We investigated whether IgA-anti-Fab or IgA-anti-F(ab')2 autoantibodies, which have been shown to correlate with severe dysfunction of the immune system, also appear in patients with head and neck cancer. Sera of 110 patients with squamous cell carcinoma, eight patients with adenoid cystic carcinoma, and 57 healthy controls were tested with an ELISA for IgA-anti-Fab autoantibody activity. Patients with head and neck cancer showed a higher IgA-anti-Fab activity (OD:399, n = 118) than healthy controls (OD: 84, n = 57, p < 0.0001). An association between stage of disease and IgA-anti-Fab activity could be established in patients with SCCHN. Stage IV patients had a significantly higher IgA-anti-Fab activity (OD: 538, n = 51) than stage 1 patients (OD: 283, n = 18, p < 0.05). Patients with stage II (OD: 293, n = 13) or stage III (OD: 379, n = 28) showed intermediate activity. Also a higher IgA-anti-Fab activity than in healthy controls was demonstrated in the eight patients with ACCHN (OD: 314, n = 8, p < 0.01). The highest IgA-anti-Fab activity was observed in eight patients with SCCHN who died within six months after testing (OD: 1004, n = 8). Similar results were obtained for IgA-anti-F(ab')2 autoantibodies. Our findings suggest an association between autoimmunity and final desintegration of physiological body functions. The occurrence of IgA-anti-Fab/IgA-anti-F(ab')2 autoantibodies might be interpreted as an aspect of immune deficiency in patients with malignant tumors of the head and neck.

Increased Serum IgA Levels in Subjects with Previous Myocardial Infarction or Other Major Ischemic Events

To ascertain whether the increase in serum IgA, which has been found to be associated with the presence of severe atherosclerotic disease, precedes or follows the occurrence of major ischemic events (MIE), we studied the serum levels of IgA as well as IgG and IgM in 145 subjects with acute or previous ischemic events and 34 controls. The subjects with previous myocardial infarction had higher IgA levels with respect to the controls, the patients with angina pectoris and those with acute myocardial infarction, while no significant differences concerning IgG and IgM were found. In the subjects with previous extracoronary events, immunoglobulin levels tended to be even higher. Overall, 30% of the subjects with previous MIE and only 3% of the controls had IgA levels over 4.5 g/l (p = 0.0018). This study indicates that total serum IgA is a marker of previous major ischemic events (protracted immune response to denatured proteins?), rather than a factor predisposing to atherosclerosis development.

The effect of sodium cromoglycate on the induction of experimental IgA nephropathy

Mesangial IgA nephropathy was experimentally induced in ddY mice by oral and parenteral administration of the poliomyelitis vaccine (POLIO), and we then tried to investigate if IgA deposition could be prevented by the concurrent use of sodium cromoglycate (SCG), which is known to inhibit the local mucosal immune reaction. Mucosal and systemic immunity could be induced by the administration of POLIO; proteinuria, increased serum IgA levels, mesangial cell proliferation, mesangial matrix widening, mesangial deposits of IgA, and large electron dense deposits in the mesangium were observed. Concurrent administration of SCG and POLIO resulted in a significant decrease in the serum IgA level and mesangial IgA deposits. The later addition or abstinence of SCG after the 70th day did not influence the glomerular mesangial IgA deposition. But the serum IgA level was still decreased by the continuous treatment of SCG even after the 70th day. Thus, mesangial IgA nephropathy simulating IgA nephropathy in humans could be induced in ddY mice using POLIO and its induction could largely be prevented by the concurrent use of SCG. However mesangial IgA deposits already present could not be cleared by the late administration of SCG.

Cirrhotic Glomerulonephritis: Incidence, Morphology, Clinical Features, and Pathogenesis

Glomerulonephritis is a little known manifestation of liver cirrhosis. Since the introduction of sophisticated immunologic staining methods, glomerular morphologic abnormalities have been noted in more than 50% of patients with cirrhosis at both necropsy and biopsy. The distinctive pathologic findings consist of glomerular mesangial IgA deposits usually accompanied by complement deposition. Increased serum IgA levels are found in over 90% of cirrhotic patients with glomerular IgA deposition. Cirrhotic glomerulonephritis is usually a clinically silent disease, however, the diagnosis can be suspected by finding proteinuria or abnormalities of the urine sediment. The pathogenesis may relate to defective hepatic processing and/or portacaval shunting of circulating immune complexes.

IgA-associated Inhibition of Polymorphonuclear Leukocyte Chemotaxis in Neutrophilic Dermatoses

The chemotactic activity of normal human polymorphonuclear leukocytes (PMNs) confronted with heat inactivated sera from patients with psoriasis as well as various chronic proliferative diseases was determined using modified Boyden chambers. By the addition of phorbol myristate acetate (PMA) at a concentration of 1 ng/ml the chemoattractant activities of the sera were greatly potentiated. However, the chemotactic migration of normal PMNs was strongly inhibited by sera from patients with long standing and wide spread psoriasis, pyoderma gangrenosum, severe acne conglobata, Sweet syndrome, and some patients with chronic arthritis following rheumatoid fever. In acute guttate psoriasis and atopic dermatitis increased migratory activities were seen. The inhibition of chemotaxis correlated with increased serum IgA levels as determined by radial immuno diffusion. Column chromatography (Sephacryl S-300) revealed serum fractions of strong inhibitory potency at a molecular weight near 200,000 Dalton. These inhibitory fractions were seen in patients with long standing neutrophil related diseases and could not be detected in normal control sera. It appears that inhibition of PMN chemotaxis is a secondary phenomenon and may play an autoregulatory role in PMN related inflammation.

Increased serum IgA levels in rats after portacaval shunt but not after portacaval transposition.

Groups of rats were submitted to end-to-side portacaval shunt, portacaval transposition or a control sham operation. There was an 18-fold increase of the IgA level in the serum of portacavally shunted rats (n = 7) at 3-6 weeks after surgery. Gel filtration revealed that this increase was predominantly due to dimeric and polymeric IgA. The serum IgM of these shunted rats, but not the IgG, was also significantly increased (twofold) above their control values. In rats subjected to portacaval transposition (n = 6), there was no significant increase of serum IgA, IgM or IgG when compared with their control values. These data confirm the active transfer, by the healthy rat liver, of IgA and, to a lesser extent, of IgM from the blood into bile. Impairment of this function, leading to the accumulation of polymeric IgA and IgM in the serum, in portacavally shunted but not portacavally transposed animals, may be related to impairment of hepatic flood flow and hepatic atrophy, shown earlier to occur in portacavally shunted but not transposed rats. Such reduction in liver cell mass could also explain the fall in transferrin levels in shunted rats.

Immunoglobulin A and M levels in premature infants with gastroenteritis.

Eleven premature babies with an infection of the gastrointestinal tract were followed from birth up to the first month of life in an attempt to correlate the effect of acute localized infections of the gut to IgA and IgM immunoglobulin synthesis. The results were compared to those of 17 prematures comparable in birthweight and gestational age with no clinical or bacteriological evidence of an intestinal infection. There was a significant increase of serum IgA and a slight but not significant increase of IgM level in infected babies as compared to the healthy group of prematures. It is suggested that micro-organisms causing localized infections of the gastrointestinal tract stimulate immunoglobulin A producing sites of the intestinal wall. This results in rapid production of secretory antibody. In the course of this localized infection, replication of bacteria in the lymphoid tissue of the intestinal wall stimulate immunologically competent cells in direct proximity to the alimentary tract, causing increased serum IgA levels.