Investigation of immune complexes formed by mitochondrial antigens containing a new lipoylated site in sera of primary biliary cholangitis patients

2021 ◽  
Author(s):  
N. Aibara ◽  
K. Ohyama ◽  
M. Nakamura ◽  
H. Nakamura ◽  
M. Tamai ◽  
...  
Keyword(s):  
Immune Complexes ◽  
Primary Biliary Cholangitis ◽  
Mitochondrial Antigens

Bile Acids and Deregulated Cholangiocyte Autophagy in Primary Biliary Cholangitis

2017 ◽  
Vol 35 (3) ◽  
pp. 210-216 ◽  
Author(s):  
Motoko Sasaki ◽  
Yasuni Nakanuma
Keyword(s):  
Bile Duct ◽  
Er Stress ◽  
Bile Acids ◽  
Cellular Senescence ◽  
Primary Biliary Cholangitis ◽  
Biliary Cirrhosis ◽  
Chemical Chaperone ◽  
Abnormal Expression ◽  
Bile Duct Lesions ◽  
Mitochondrial Antigens

Background: Primary biliary cholangitis (PBC) is characterized by a high prevalence of serum anti-mitochondrial antibodies against the E2 subunit of the pyruvate dehydrogenase complex and bile duct lesions called chronic non-suppurative destructive cholangitis (CNSDC) in small bile ducts, eventually followed by extensive bile duct loss and biliary cirrhosis. Macroautophagy (a major type of autophagy) is a process of cellular self-digestion that plays a critical role in energy homeostasis and in the cytoprotection to various stresses. Deregulated autophagy is thought to be associated with various human diseases. Key Messages: Accumulating evidences suggest that deregulated autophagy may be a central player in the pathogenesis of PBC. Damaged cholangiocytes involved in CNSDC show vesicular expression of autophagy marker LC3 and accumulation of p62/sequestosome-1, suggesting deregulated autophagy. Deregulated autophagy may be involved in the autoimmune process via the abnormal expression of mitochondrial antigens and also in cholangiocyte senescence in bile duct lesions in PBC. In vitro study showed that hydrophobic bile acids, such as glycochenodeoxycholic acid (GCDC), as well as serum deprivation and oxidative stress, cause autophagy, deregulated autophagy and abnormal expression of mitochondrial antigens followed by cellular senescence in cholangiocytes. Although exact mechanisms of deregulated autophagy remain to be clarified, endoplasmic reticulum (ER) stress may be a plausible cause of deregulated autophagy induced by GCDC in cholangiocytes. Impaired ‘biliary bicarbonate umbrella' may further exacerbate the toxicity of GCDC to cholangiocytes. Interestingly, pretreatment with ursodeoxycholic acid (UDCA) and tauro-UDCA, which is a chemical chaperone enhancing the adaptive capacity of the ER, significantly suppressed ER stress, deregulated autophagy and cellular senescence induced by GCDC and other stresses in cholangiocytes. Conclusions: GCDC may play a role in the occurrence of deregulated autophagy and cellular senescence at least partly through the induction of ER stress in PBC. Deregulated autophagy and cellular senescence can be a promising therapeutic target in PBC.

FcRL4+ b cells are associated with inflamed bile ducts in patients with primary biliary cholangitis and locally capture IGA immune complexes

2020 ◽  
Vol 73 ◽  
pp. S205
Author(s):  
Yuxin Susan Liu ◽  
Karim Raza ◽  
Evaggelia Liaskou ◽  
Stefan G. Hübscher ◽  
Gideon Hirschfield ◽  
...  
Keyword(s):  
B Cells ◽  
Immune Complexes ◽  
Bile Ducts ◽  
Primary Biliary Cholangitis ◽  
Iga Immune Complexes

Platelets release mitochondrial antigens in systemic lupus erythematosus

2021 ◽  
Vol 13 (581) ◽  
pp. eaav5928 ◽  
Author(s):  
Imene Melki ◽  
Isabelle Allaeys ◽  
Nicolas Tessandier ◽  
Tania Lévesque ◽  
Nathalie Cloutier ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Immune Complexes ◽  
Fluorescent Protein ◽  
Red Fluorescent Protein ◽  
Systemic Lupus ◽  
Fibrinogen Receptor ◽  
Mitochondrial Antigens ◽  
Stimulation Of

The accumulation of DNA and nuclear components in blood and their recognition by autoantibodies play a central role in the pathophysiology of systemic lupus erythematosus (SLE). Despite the efforts, the sources of circulating autoantigens in SLE are still unclear. Here, we show that in SLE, platelets release mitochondrial DNA, the majority of which is associated with the extracellular mitochondrial organelle. Mitochondrial release in patients with SLE correlates with platelet degranulation. This process requires the stimulation of platelet FcγRIIA, a receptor for immune complexes. Because mice lack FcγRIIA and murine platelets are completely devoid of receptor capable of binding IgG-containing immune complexes, we used transgenic mice expressing FcγRIIA for our in vivo investigations. FcγRIIA expression in lupus-prone mice led to the recruitment of platelets in kidneys and to the release of mitochondria in vivo. Using a reporter mouse with red fluorescent protein targeted to the mitochondrion, we confirmed platelets as a source of extracellular mitochondria driven by FcγRIIA and its cosignaling by the fibrinogen receptor α2bβ3 in vivo. These findings suggest that platelets might be a key source of mitochondrial antigens in SLE and might be a therapeutic target for treating SLE.

The Pathogenesis of Primary Biliary Cholangitis: A Comprehensive Review

2019 ◽  
Vol 40 (01) ◽  
pp. 034-048 ◽  
Author(s):  
Ana Lleo ◽  
Patrick S.C. Leung ◽  
Gideon M. Hirschfield ◽  
Eric M. Gershwin
Keyword(s):  
Active Role ◽  
Medium Size ◽  
Primary Biliary Cholangitis ◽  
Cholestatic Liver Disease ◽  
Key Factors ◽  
Intrahepatic Bile Ducts ◽  
Autoimmune Destruction ◽  
Chronic Cholestasis ◽  
Immune Mediated ◽  
Mitochondrial Antigens

AbstractPrimary biliary cholangitis (PBC) is a chronic cholestatic liver disease characterized by autoimmune destruction of small to medium size intrahepatic bile ducts. The etiology of PBC remains unknown and pathogenesis features immune-mediated biliary injury, alongside the consequences of chronic cholestasis. PBC is strongly associated with the loss of immune tolerance against mitochondrial antigens and the subsequent presence of an articulated immunologic response that involves both humoral and cellular responses. Both environmental factors and genetic variants increase PBC susceptibility. Biliary epithelial cells have often been considered a passive target of the immune attack in PBC; however, cholangiocyte dedifferentiation, senescence, stress, and deoxyribonucleic acid damage have been recognized to play an active role in the pathogenesis of PBC. This review highlights and discusses the most relevant pathogenetic mechanisms in PBC, focusing on the key factors that lead to the onset of cholestasis and immune activation.

Immune complexes in primary biliary cirrhosis contain mitochondrial antigens

1982 ◽  
Vol 22 (3) ◽  
pp. 394-399 ◽  
Author(s):  
E. Penner ◽  
H. Goldenberg ◽  
B. Albini ◽  
M.M. Weiser ◽  
F. Milgrom
Keyword(s):  
Primary Biliary Cirrhosis ◽  
Immune Complexes ◽  
Biliary Cirrhosis ◽  
Mitochondrial Antigens

A Sensitive On-Grid Immunoelectron Microscopic Procedure for Diagnosis of Rotavirus Infection

1980 ◽  
Vol 38 ◽  
pp. 506-507
Author(s):  
M. F. Miller ◽  
A. R. Rubenstein
Keyword(s):  
Electron Microscopy ◽  
Specific Antibody ◽  
Immune Complexes ◽  
Acute Gastroenteritis ◽  
Plant Viruses ◽  
Aggregation Process ◽  
Microscopic Technique ◽  
Fecal Material ◽  
Present Communication ◽  
Number Of Particles

Studies of rotavirus particles in humans, monkeys and various non-primates with acute gastroenteritis have involved detection of virus in fecal material by electron microscopy. The EM techniques most commonly employed have been the conventional negative staining (Fig. 1) and immune aggregation (Fig. 2) procedures. Both methods are somewhat insensitive and can most reliably be applied to samples containing large quantities of virus either naturaLly or as a result of concentration by ultracentrifugation. The formation of immune complexes by specific antibody in the immune aggregation procedures confirms the rotavirus diagnosis, but the number of particles per given microscope field is effectively reduced by the aggregation process. In the present communication, we describe use of an on-grid immunoelectron microscopic technique in which rotavirus particles are mounted onto microscope grids that were pre-coated with specific antibody. The technique is a modification of a method originalLy introduced by Derrick (1) for studies of plant viruses.

Localization of Immune Complexes in the Basement Membrane of the Ductuli Efferentes of the Rhesus Monkey

1980 ◽  
Vol 38 ◽  
pp. 456-457
Author(s):  
D. Marsh
Keyword(s):  
Basement Membrane ◽  
Fluorescence Microscopy ◽  
Rhesus Monkey ◽  
Immune Complex ◽  
Immune Complexes ◽  
Vas Deferens ◽  
Frozen Sections ◽  
Efferent Ducts ◽  
Complex Deposition ◽  
Sperm Antibodies

As a result of vasectomy, spermatozoa are confined to the epididymis and vas deferens, where they degenerate, releasing antigens that enter the circulation or are engulfed by macrophages. Multiple antigens of the sperm can elicit production of autoantibodies; circulating anti-sperm antibodies are found in a large percentage of vasectomized men, indicating the immunogenicity of the sperm. The increased prevalence of macrophages in the liomen of the rhesus monkey testicular efferent ducts after vasectomy led to further study of this region. Frozen sections were used for evaluation of immunopathological status by fluorescence microscopy with fluorescein-conjugated antibody. Subsequent granular deposits of immune complexes were revealed by positive immunofluorescence staining for complement. The immune complex deposition in the basement membrane surrounding the efferent ducts implies that this region is involved in antigen leakage (Fig. 1).

Coagulation and Fibrinolysis Study in Systemic Lupus erythematosus: Haematological, Urinary and Tissue Parameters

1981 ◽  
Vol 46 (03) ◽  
pp. 575-580 ◽  
Author(s):  
P Stratta ◽  
C Canavese ◽  
P Valmaggia ◽  
M Rotunno ◽  
E Levi ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Immune Complexes ◽  
Acute Stage ◽  
Systemic Lupus ◽  
Immunological Activity ◽  
Coagulation Abnormalities ◽  
Coagulation And Fibrinolysis

SummaryHaematochemical, urinary and tissue parameters were examined in the elaboration of the coagulation and fibrinolysis profile in 33 cases of systemic lupus erythematosus in different stages of the disease. Coagulation abnormalities varied from hypo- to hyper-coagulabitity, these being often associated in the same patient, either simultaneously or at different stages of the disease. Activation of coagulation, closely related to the immunological activity of the disease, was present in 80% cases in the acute stage, and 36% of those in the remission stage. The lupus-like anticoagulant was not much involved, and platelets were the prime figures in the haemostatic abnormalities of lupus, those being the preferred target of direct antibody activities, or possibly of immune complexes as well. Activation of the coagulatory cascade is not uncommonly accompanied by a thrombophilic tendency coupled with signs of consumption, this being the expression of a continuously stimulated haemostatic balance.

Effect of Cyclic AMP and Cyclic GMP on Thromboplastin (Factor III) Synthesis in Human Monocytes In Vitro

1983 ◽  
Vol 50 (04) ◽  
pp. 804-809 ◽  
Author(s):  
Torstein Lyberg
Keyword(s):  
Cyclic Amp ◽  
Cyclic Gmp ◽  
Immune Complexes ◽  
Phosphodiesterase Inhibitors ◽  
Inhibitory Effect ◽  
Intracellular Camp ◽  
Human Monocytes ◽  
Purified Protein Derivative ◽  
A 23187

SummaryHuman monocytes in vitro respond to various agents (immune complexes, lectins, endotoxin, the divalent ionophore A 23187, 12-0-tetradecanoyl-phorbol 13-acetate [TPA], purified protein derivative [PPD] of Bacille Calmette-Guerin) with an increased synthesis of the protein component of thromboplastin. The effect of cyclic AMP and cyclic GMP on this response has been studied. Dibutyryl-cyclic AMP, prostaglandin E1 and the phosphodiesterase inhibitors 3-butyl-1-methyl-xanthine (MIX) and rac -4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone (Ro 201724), separately and in combination have a pronounced inhibitory effect on the response to immune complexes and PPD, and a moderate effect on the response to endotoxin and lectins. The effect on TPA response and on the response to A 23187 was slight. Dibutyryl-cyclic GMP (1 mM) gave a slight inhibition of the TPA arid IC response, but had essentially no effect on the response to other inducers. The intracellular cAMP level increased when monocytes were incubated with IC, TPA or A 23187 followed by a decrease to basal levels within 1-2 hr, whereas lectin (PHA) and PPD did not induce such changes. The cAMP response to endotoxin varied. Stimulation with IC induced an increase in monocyte cGMP levels, whereas the other stimulants did not cause such changes.

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