scholarly journals Abundance and nuclear antigen reactivity of intestinal and fecal Immunoglobulin A in lupus-prone mice at younger ages correlate with the onset of eventual systemic autoimmunity

2020 ◽  
Author(s):  
Wei Sun ◽  
Radhika Gudi ◽  
Benjamin M. Johnson ◽  
Chenthamarakshan Vasu

AbstractOur recent studies, using (SWRxNZB)F1 (SNF1) mice, showed a potential contribution of the gut microbiota and pro-inflammatory immune responses of the gut mucosa to systemic autoimmunity in lupus. Here, using this mouse model, we determined the abundance and the nAg reactivity of IgA antibody produced in the intestine under lupus susceptibility. Intestinal lymphoid tissues from SNF1 mice, females particularly, showed significantly higher frequencies of nAg (dsDNA and nucleohistone) reactive IgA producing B cells compared to B6 females. Most importantly, younger age fecal IgA -abundance and - nAg reactivity of lupus-prone mice showed a positive correlation with eventual systemic autoimmunity and proteinuria onset. Depletion of gut microbiota in SNF1 mice resulted in the diminished production of IgA in the intestine and the nAg reactivity of these antibodies. Overall, these observations show that fecal IgA features, nuclear antigen reactivity particularly, at preclinical stages/in at-risk subjects could be predictive of autoimmune progression.

1994 ◽  
Vol 5 (6) ◽  
pp. 1400-1406
Author(s):  
F Eitner ◽  
M Schulze ◽  
R Brunkhorst ◽  
K M Koch ◽  
J Floege

Immunoglobulin A (IgA)-fibronectin complexes have been proposed as specific serologic markers of IgA nephropathy. They have been detected by the use of ELISA composed of an immobilized antifibronectin antibody (or albumin as a negative control) and an enzyme-conjugated anti-IgA antibody (antifibronectin capture assay). By the use of this type of assay, plasma samples from 32 normal controls, 38 IgA nephropathy patients, and 81 patients with other types of glomerulonephritis were analyzed. Extinction values in IgA nephropathy patients were higher (P = 0.06) than in patients with other glomerulonephritis types and significantly higher than in normals. Markedly lower values were obtained when the plates were coated with albumin. However, when the antifibronectin antibody was replaced by normal IgG or F(ab')2 fragments, almost identical extinctions were measured. The use of different antifibronectin antibodies, IgG, ELISA plates, or blocking regimens did not modify these results. Extinction values could not be suppressed by the addition of exogenous fibronectin. Similar extinctions were observed when plasma samples were replaced by physiologic concentrations of fibronectin-free IgA. Extinction values measured in the plasma samples correlated significantly with IgA concentrations in plasma as analyzed by nephelometry. A collagen binding assay, a second type of assay used to measure IgA-fibronectin complexes, also allowed the detection of fibronectin-free IgA, and again, extinctions measured in plasma could not be suppressed by exogenous fibronectin. In conclusion, both antifibronectin capture ELISA and collagen binding assays do not specifically detect only IgA-fibronectin complexes, but also total plasma IgA, which is frequently, but nonspecifically, elevated in IgA nephropathy.(ABSTRACT TRUNCATED AT 250 WORDS)


2021 ◽  
Vol 11 ◽  
Author(s):  
Jicheng Li ◽  
Yiwen Cao ◽  
Ruirui Lu ◽  
Honglian Li ◽  
Yu Pang ◽  
...  

Immunoglobulin A nephropathy (IgAN), an autoimmune renal disease with complicated pathogenesis, is one of the principal reasons for end-stage renal disease in the clinic. Evidence has linked apparent alterations in the components of the microbiome and metabolome to renal disease in rats. However, thus far, there is insufficient evidence that supports the potential relationship between gut microbiome, circulating metabolites, and IgAN. This study was designed to probe the effects of IgAN on intestinal microecology and metabolic phenotypes and to understand the possible underlying mechanisms. Fecal and serum samples were collected from IgAN rats. Composition of the gut microbiota and biochemical changes in the metabolites was analyzed using 16S rDNA sequencing and untargeted metabolomics. The IgAN rats exhibited renal insufficiency and increased concentration of 24-h urine protein, in addition to deposition of IgA and IgG immune complexes in the kidney tissues. There was a disturbance in the balance of gut microbiota in IgAN rats, which was remarkably associated with renal damage. Marked changes in microbial structure and function were accompanied by apparent alterations in 1,403 serum metabolites, associated with the disorder of energy, carbohydrate, and nucleotide metabolisms. Administration of Zhen Wu Tang ameliorated microbial dysbiosis and attenuated the renal damage. Besides, treatment with Zhen Wu Tang modulated the metabolic phenotype perturbation in case of gut microbiota dysbiosis in IgAN rats. In conclusion, these findings provided a comprehensive understanding of the potential relationship between the intestinal microbiota and metabolic phenotypes in rats with IgAN. Elucidation of the intestinal microbiota composition and metabolic signature alterations could identify predictive biomarkers for disease diagnosis and progression, which might contribute to providing therapeutic strategies for IgAN.


2005 ◽  
Vol 12 (10) ◽  
pp. 1235-1237 ◽  
Author(s):  
M. Nawa ◽  
T. Takasaki ◽  
M. Ito ◽  
S. Inoue ◽  
K. Morita ◽  
...  

ABSTRACT We determined the usefulness of an immunoglobulin A (IgA) antibody-capture enzyme-linked immunosorbent assay for serodiagnosis of dengue virus infections. The results indicate that the presence of IgA and IgM in serum samples assures recent primary dengue virus infection even with a single serum sample.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Hongwei Wu ◽  
Yong Dai ◽  
Fanna Liu ◽  
Lianghong Yin

Abstract Background and Aims Immunoglobulin A nephropathy (IgAN) is the most common form of primary glomerulonephritis. Intestinal bacteria and their metabolites have been implicated in various diseases. Improved understanding of the gut microbiota and its metabolic capabilities will facilitate development of diagnostic, therapeutic, and prognostic methods for IgAN Method We identified gut microbiota and metabolite biomarkers of IgAN by analyzing microbiomes and metabolomes of fecal and serum samples of IgAN patients and healthy controls using 16s ribosomal RNA gene sequencing and liquid chromatography-tandem mass spectrometry, respectively, and bioinformatics approaches Results We found that relative abundances of Streptococcus and Enterococcus were higher in IgAN patients, whereas Bacteroidetes and Bacteroides were lower. The changes in gut microbiota affected metabolism and absorbance of microbiota-associated metabolites of IgAN patients, in particular polyunsaturated fatty acids, free amino acids and oligopeptides, and activated the phenylalanine metabolism pathway. Also, 5-hydroxyeicosatetraenoic acid and 5-hydroxy-6E,8Z,11Z-eicosatrienoic acid were proved to be associated with the classification of segmental glomerular sclerosis but not 24h urine protein and estimated glomerular filtration rate. Conclusion Our findings demonstrate an interplay between intestinal bacteria and metabolites in IgAN. The identified metabolites may have diagnostic and therapeutic applications.


2011 ◽  
Vol 23 (1) ◽  
pp. 142-151 ◽  
Author(s):  
S.J. Challacombe ◽  
P.L. Fidel ◽  
S. Tugizov ◽  
L. Tao ◽  
S.M. Wahl

Most HIV infections are transmitted across mucosal epithelium. An area of fundamental importance is understanding the role of innate and specific mucosal immunity in susceptibility or protection against HIV infection, as well as the effect of HIV infection on mucosal immunity, which leads to increased susceptibility to bacterial, fungal, and viral infections of oral and other mucosae. This workshop attempted to address 5 basic issues—namely, HIV acquisition across mucosal surfaces, innate and adaptive immunity in HIV resistance, antiviral activity of breast milk as a model mucosal fluid, neutralizing immunoglobulin A antibodies against HIV, and progress toward a mucosal vaccine against HIV. The workshop attendants agreed that progress had been made in each area covered, with much recent information. However, these advances revealed how little work had been performed on stratified squamous epithelium compared with columnar epithelium, and the attendants identified several important biological questions that had not been addressed. It is increasingly clear that innate immunity has an important biological role, although basic understanding of the mechanisms of normal homeostasis is still being investigated. Application of the emerging knowledge was lacking with regard to homeostatic mucosal immunity to HIV and its role in changing this homeostasis. With regard to breast milk, a series of studies have demonstrated the differences between transmitters and nontransmitters, although whether these findings could be generalized to other secretions such as saliva was less clear. Important progress toward an oral mucosal HIV vaccine has been made, demonstrating proof of principle for administering vaccine candidates into oral lymphoid tissues to trigger anti-HIV local and systemic immune responses. Similarly, experimental data emphasized the central role of neutralizing antibodies to prevent HIV infection via mucosal routes.


2019 ◽  
Vol 38 (2) ◽  
pp. 55-64 ◽  
Author(s):  
Teresia Aluoch MUHOMAH ◽  
Naoki NISHINO ◽  
Emiko KATSUMATA ◽  
Wu HAOMING ◽  
Takeshi TSURUTA

1989 ◽  
Vol 98 (7) ◽  
pp. 523-529 ◽  
Author(s):  
Noritake Watanabe ◽  
Hirofumi Kato ◽  
Goro Mogi

We investigated the actual processes for activating respiratory mucosal immunity. Hartley guinea pigs were immunized with particulate antigen of dinitrophenylated ovalbumin into the duodenum (group A), trachea (group B), and nasal cavity (group C) 1 week after systemic priming with the soluble antigen. The control animals (group D) received only systemic priming. Immunoglobulin A antibody titers in nasal secretions and saliva from groups A and B significantly exceeded those of groups C and D (p<.01). Many antigen-specific IgA-forming cells were detected in the respiratory and gastrointestinal mucosae of groups A and B. Following duodenal immunization, the appearance of antigen-specific IgA-forming cells in Peyer's patches preceded those in mesenteric and hilar lymph nodes, while they simultaneously appeared in the lymphoid tissues after tracheal immunization. These findings suggest that intratracheal immunization mainly stimulates bronchus-associated lymphoid tissue as a source of IgA precursors, as intraduodenal immunization stimulates gut-associated lymphoid tissue.


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