Antigenic Substances Research Articles

Chitosan from the base of Flammulina velutipes stipe alleviates oral Candida albicans infection via modulating Th-17 cell differentiation and Streptococcus mutans

The base of Flammulina velutipes (F. velutipes) stipe are agricultural wastes generated during the cultivation of edible fungus F. velutipes with high amount of chitin. Herein, this study firstly prepared chitosan from the base of F. velutipes stipe (FVC) and its structure was identified. It was confirmed that FVC acted as an antigenic substance to activate the immune system in vivo and in vitro, drive T cells to differentiate into Th-17 cells, and establish an effective mucosal immune barrier in the oral cavity, thus inhibited C. albicans infection; On the other hand, FVC maintained the oral flora stability and significantly reduced the abundance of Streptococcus spp., which was closely related to C. albicans infection. On this basis, the inhibitory effects of FVC on oral pathogens Streptococcus mutans and Lactobacillus casei associated with C. albicans infection were further verified, and it was demonstrated that FVC effectively interfered with the growth of pathogenic bacteria by inducing the production of intracellular ROS to damage bacterial cells. Therefore, FVC may be potentially exploited as a novel approach to the prevention and treatment of oral C. albicans infection.

Nanozymes in cancer immunotherapy: metabolic disruption and therapeutic synergy.

Over the past decade, there has been a growing emphasis on investigating the role of immunotherapy in cancer treatment. However, it faces challenges such as limited efficacy, a diminished response rate, and serious adverse effects. Nanozymes, a subset of nanomaterials, demonstrate boundless potential in cancer catalytic therapy for their tunable activity, enhanced stability, and cost-effectiveness. By selectively targeting the metabolic vulnerabilities of tumors, they can effectively intensify the destruction of tumor cells and promote the release of antigenic substances, thereby eliciting immune clearance responses and impeding tumor progression. Combined with other therapies, they synergistically enhance the efficacy of immunotherapy. Hence, a large number of metabolism-regulating nanozymes with synergistic immunotherapeutic effects have been developed. This review summarizes recent advancements in cancer immunotherapy facilitated by nanozymes, focusing on engineering nanozymes to potentiate antitumor immune responses by disturbing tumor metabolism and performing synergistic treatment. The challenges and prospects in this field are outlined. We aim to provide guidance for nanozyme-mediated immunotherapy and pave the way for achieving durable tumor eradication.

Possible mechanisms of phlebitis-like abnormal reaction (PLAR) after cyanoacrylate obliteration of varicose veins

Based on their own research and a review of the literature, the authors analyze the possible cellular mechanisms of the development of an inflammatory reaction after the obliteration of varicose veins with cyanoarylate adhesive compounds (CAO), which received the name phlebitis- Like abnormal Reaction (PLAR) in foreign sources. Despite the existing opinion about the “abnormal” nature of the inflammatory reaction, it is noted that the main stages of its development are fully consistent with the currently known molecular and cellular mechanisms of the response of biological tissues to contact with a foreign antigenic substance and are of a natural nature. The cause of the development of acute alterative inflammation in the vein wall is the direct contact of the endothelium with an aggressive environment, which is cyanoacrylate. A specific feature of the development of chronic inflammation in the vein wall is its productive interdaily character, which is replaced by proliferative processes. The main role in the development of successive stages of PLAR development is played by monocytic, mast and giant cells of foreign bodies, as well as the mechanisms underlying the regulation of the functional activity of these cells. During the period of cyanoacrylate biodegradation, its cellular environment corresponds to all morphological features of a phagocytoma, whose activity decreases with the biodegradation of cyanoacrylate with simultaneous connective tissue proliferation. The development of possible chronic granulomatous inflammation is based on a local autoimmune process associated with the formation of giant multinucleated epithelioid cells (Langerhans cells). In conclusion, it is emphasized that today, when using various cyanoacrylate compounds for the purpose of adhesive obliteration of veins, taking into account the accumulated clinical data and morphological studies, the final answers to the existing reasonable objections about the complete safety of the use of cyanoacrylates in clinical practice should be given by fundamental immunohistochemical and genetic studies.

A STUDY OF ASSOCIATION OF ABO/RH BLOOD GROUPS WITH TYPE 2 DIABETES MELLITUS AND ITS MICROVASCULAR COMPLICATIONS

Diabetes mellitus (DM) is a chronic disease with an estimated 537 million people having diabetes worldwide with Type 2 Diabetes Mellitus making up about 90% of the cases. It is the fastest growing non communicable disease in the world. Its pathophysiology is linked to multiple genetic and environmental causes. Long term uncontrolled diabetes can cause many micro and macro vascular complications. Microvascular complications like neuropathy, retinopathy and nephropathy are linked more closely to control of blood sugar levels. ABO blood groups are polymorphic, inherited, antigenic substances found on the surface of red blood cells in addition to other tissues. Specic ABO blood groups are found to have predisposition for some specic diseases such as gastric and duodenal ulcer and some vascular diseases. In this study we aim to study the correlation between the incidence and various microvascular complications of diabetes with specic ABO blood groups.

A sandwich electrochemical immunosensor based on MXene@dual MOFs for detection of tumor marker CA125.

The detection signal of carbohydrate antigen 125 (CA125) can be quantitatively amplified via the dual metal-organic framework (MOF) sandwich strategy. We propose a versatile method for synthesizing uniform MXene and MIL-101(Fe)-NH2 composites that combine the advantages of both materials to build a base layer with superb performance. MXene exhibits excellent electrical conductivity and high surface area. The mesoporous MIL-101(Fe)-NH2 not only increases the loading capacity of the primary antibody but also possesses the catalytic activity of the metal center (Fe). UiO66 loaded with methylene blue (MB) was fabricated as an electrochemical immunosensor signal tag to enable the detection of CA125. The mixture of MXene and MIL-101(Fe)-NH2 prepared as the substrate was fixed by chitosan rich in amino groups. As the signal amplification sector, UiO66@MB enhanced secondary antibody loading capacity and generated a redox signal enabling the detection of antigenic substances. The proposed electrochemical immunosensor demonstrated high sensitivity with a low limit of detection (LOD) of 0.006 U/mL. Therefore, the dual MOF sandwich-based immunosensor provides a novel method for the early diagnosis of CA125.

A Novel Mathematical Model That Predicts the Protection Time of SARS-CoV-2 Antibodies.

Infectious diseases such as SARS-CoV-2 pose a considerable threat to public health. Constructing a reliable mathematical model helps us quantitatively explain the kinetic characteristics of antibody-virus interactions. A novel and robust model is developed to integrate antibody dynamics with virus dynamics based on a comprehensive understanding of immunology principles. This model explicitly formulizes the pernicious effect of the antibody, together with a positive feedback stimulation of the virus-antibody complex on the antibody regeneration. Besides providing quantitative insights into antibody and virus dynamics, it demonstrates good adaptivity in recapturing the virus-antibody interaction. It is proposed that the environmental antigenic substances help maintain the memory cell level and the corresponding neutralizing antibodies secreted by those memory cells. A broader application is also visualized in predicting the antibody protection time caused by a natural infection. Suitable binding antibodies and the presence of massive environmental antigenic substances would prolong the protection time against breakthrough infection. The model also displays excellent fitness and provides good explanations for antibody selection, antibody interference, and self-reinfection. It helps elucidate how our immune system efficiently develops neutralizing antibodies with good binding kinetics. It provides a reasonable explanation for the lower SARS-CoV-2 mortality in the population that was vaccinated with other vaccines. It is inferred that the best strategy for prolonging the vaccine protection time is not repeated inoculation but a directed induction of fast-binding antibodies. Eventually, this model will inform the future construction of an optimal mathematical model and help us fight against those infectious diseases.

THE EXPERIMENTAL DETERMINATION OF THE NUMBER OF FREEZING STAGES OF CANDIDA TROPICALIS FUNGAL CELLS FOR THEIR DESTRUCTION AND OBTAINING OF PROTEINS AND POLYSACCHARIDES

Candidiasis is a disease that occurs due to excessive growth of the Candida fungus. Several types of this pathogen are known, each of which can cause damage to various organs and systems. Recently, there have been reports of the loss of sensitivity of Candida fungi to most of antifungal drugs that have been used for more than 40 years. An alternative to antifungal drugs for candidiasis can be the use of a vaccine for the prevention and treatment of candidal infection. In our opinion, it is promising to use a candidal vaccine based on a subunit vaccine that contains fragments of a microorganism without ballast substances. Cell fragments of Candida fungi that have antigenic properties include proteins and polysaccharides. To isolate antigenic substances from Candida fungal cells, we chose freezing as the method of destruction. The aim of this work was to experimentally substantiate the number of freezing stages for the destruction of C. tropicalis АТСС 20336 fungi cells and the subsequent production of proteins and polysaccharides. To determine the optimal number of freezing stages in the temperature range from (25 ± 2)°С to (-25 ± 2)°С, in order to destroy the cells of C. tropicalis fungi, the studies were conducted with freezing stages 3, 4, 5, and 6. Centrifugation was used to separate the excess components. Then the preliminary and sterilizing filtration was performed on membrane filters with pore diameters of 0.45 μm and 0.22 μm. The content of protein, polysaccharides and monosaccharides were determined in each case. The protein content was determined according to the State Pharmacopoeia of Ukraine (SPhU). To determine polysaccharides, a reaction with phenol and sulfuric acid was performed. Chromatographic studies of monosaccharides were conducted using paper chromatography according to the SPhU. Based on the results of the research, it was found that solutions obtained at stages 5 and 6 of freezing the biomass of C. tropicalis fungi cells at a temperature from (25 ± 2) °C to (-25 ± 2) °C contained the highest amount of proteins and polysaccharides. It is likely that with these number of stages for freezing the biomass of C. tropicalis fungi cells, active substances are released from all layers of Candida fungi cells. Thus, it can be concluded that five stages of freezing are the optimal number that ensures the maximum extraction of polysaccharides and proteins quickly and economically.

BLOOD GROUP DETECTION USING DEEP LEARNING

Division and counting of platelets are considered as a critical development that helps with isolating features to dissect a few specific diseases. The manual counting of RBCs in tiny pictures is an incredibly grim, dreary, and misguided system. Modified examination will allow hematologist experts to perform faster and all the more definitively. Assessment of blood characterization plays a basic get-together in the helpful field for any treatment. Misleading bonding of blood will incite various issues. This structure gives straightforward and fast techniques for recognizing verification of blood characterizations and Rhesus factor none prominently. Our construction is taken a stab at a couple of veritable instructive assortments of various individual pictures of human fingertip pictures. Blood characterization is gathered ward on the closeness and nonappearance of specific natural substances called antibodies and moreover reliant upon the proximity or nonattendance of obtained antigenic protein substances on the surfaces of the erythrocytes in the body. Thusly by using the optical properties of the antigens and the rhesus ascertain present the blood, the blood social events can be requested.

Blood Group Typing of Students of Govt.Degree College Doda, Jammu and Kashmir: A Case Study

ABO blood group system was the 1st human blood group system to be discovered. Blood group is an integral part of clinical diagnosis using various hematological techniques to understand hematological disorders. Blood type is a classification of blood based on the presence and absence of antibodies and inherited antigenic substance on the surface of red blood cells. It is important to have clear information on blood groups in case of blood transfusion and related matters. It is also mandatory to have complete history of patient including the blood grouping and for the establishment and maintenance of blood banks.The present study was carried out among the students of Govt.Degree College Doda, Jammu and Kashmir from 10th of May to 20th of June 2022 in which 950 students participated .The collected data was statistically analysed in the form of Pie charts and bar diagrams by using Microsoft Excel software.

A Comprehensive Prognostic Analysis of Tumor-Related Blood Group Antigens in Pan-Cancers Suggests That SEMA7A as a Novel Biomarker in Kidney Renal Clear Cell Carcinoma.

Blood group antigen is a class of heritable antigenic substances present on the erythrocyte membrane. However, the role of blood group antigens in cancer prognosis is still largely unclear. In this study, we investigated the expression of 33 blood group antigen genes and their association with the prognosis of 30 types of cancers in 31,870 tumor tissue samples. Our results revealed that blood group antigens are abnormally expressed in a variety of cancers. The high expression of these antigen genes was mainly related to the activation of the epithelial-mesenchymal transition (EMT) pathway. High expression of seven antigen genes, i.e., FUT7, AQP1, P1, C4A, AQP3, KEL and DARC, were significantly associated with good OS (Overall Survival) in six types of cancers, while ten genes, i.e., AQP1, P1, C4A, AQP3, BSG, CD44, CD151, LU, FUT2, and SEMA7A, were associated with poor OS in three types of cancers. Kidney renal clear cell carcinoma (KIRC) is associated with the largest number (14 genes) of prognostic antigen genes, i.e., CD44, CD151, SEMA7A, FUT7, CR1, AQP1, GYPA, FUT3, FUT6, FUT1, SLC14A1, ERMAP, C4A, and B3GALT3. High expression of SEMA7A gene was significantly correlated with a poor prognosis of KIRC in this analysis but has not been reported previously. SEMA7A might be a putative biomarker for poor prognosis in KIRC. In conclusion, our analysis indicates that blood group antigens may play functional important roles in tumorigenesis, progression, and especially prognosis. These results provide data to support prognostic marker development and future clinical management.

The Outer Membrane Proteins and Their Synergy Triggered the Protective Effects against Pathogenic Escherichia coli.

Colibacillosis caused by pathogenic Escherichia coli (E. coli) is one of the most serious infectious diseases, causing an extensive burden on animal husbandry and the human healthcare system. Vaccination is one of the ideal ways to prevent E. coli infection. In this work, recombinant outer membrane protein A (rOmpA), outer membrane protein C (rOmpC) and BamA (rBamA) from E. coli O78 (CVCC CAU0768) were expressed in a prokaryotic expression system with the concentration of 1–2 mg/mL after purification. Considerable immune responses could be triggered in mice that were immunized with these recombinant proteins, high antibody titers, high total IgG level and various antibody isotypes were detected in antisera after booster immunizations. Moreover, mice immunized with several recombinant proteins in combination showed a higher survival rate with the challenge of homologous strain E. coli O78 and a more significant cross-protection effect against heterologous strain E. coli O157:H7 (CICC 21530) in vivo than those of immunized alone. The antisera from immunized mice showed high affinity to multiple strains of Escherichia, Shigella and Salmonella in vitro, indicating that recombinant outer membrane proteins from E. coli O78 had the potential to be developed into universal antigenic substances against not only E. coli but also a variety of Gram-negative bacteria. rOmpA was considered as the most immunogenic protein in this work and the combination of different proteins could further enhance the immune response of immunized mice, which provided the reference for the construction of novel antigens with higher efficiency.

Dynamic study of the pathogen-immune system interaction with natural delaying effects and protein therapy

<abstract> <p>This study aims to propose and analyze a mathematical model of the competitive interaction of the pathogen-immune system. Some effects of the existence of natural delays and the addition of therapeutic proteins are considered in the model. A delay arises from the indirect response of the host body when a pathogen invades. The other comes from the maturation of immune cells to produce immune memory cells since the immune system and antigenic substances responsible for provoking the production of immune memory cells. Analytical investigations suggest several sufficient conditions for the existence of a positive steady-state solution. There is a critical pair of delays at which oscillatory behavior appears around the positive steady-state solution. Numerical simulations were carried out to describe the results of the analysis and show that the proposed model can describe the speed of pathogen eradication due to the addition of therapeutic proteins as antigenic substances.</p> </abstract>

Polymer chimera of stapled oncolytic peptide coupled with anti-PD-L1 peptide boosts immunotherapy of colorectal cancer

Rationale: Scarce tumor mutation burden and neoantigens create tremendous obstacles for an effective immunotherapy of colorectal cancer (CRC). Oncolytic peptides rise as a promising therapeutic approach that boosts tumor-specific immune responses by inducing antigenic substances. However, the clinical application of oncolytic peptides has been hindered because of structural instability, proteolytic degradation, and undesired toxicity when administered systemically.Methods: Based on wasp venom peptide, an optimized stapled oncolytic peptide MP9 was developed with rigid α-helix, protease-resistance, and CRC cell cytotoxicity. By incorporating four functional motifs that include D-peptidomimetic inhibitor of PD-L1, matrix metalloproteinase-2 (MMP-2) cleavable spacer, and MP9 with 4-arm PEG, a novel peptide-polymer conjugate (PEG-MP9-aPDL1) was obtained and identified as the most promising systemic delivery vehicle with PD-L1 targeting specificity and favorable pharmacokinetic properties.Results: We demonstrated that PEG-MP9-aPDL1-driven oncolysis induces a panel of immunogenic cell death (ICD)-relevant damage-associated molecular patterns (DAMPs) both in vitro and in vivo, which are key elements for immunotherapy with PD-L1 inhibitor. Further, PEG-MP9-aPDL1 exhibited prominent immunotherapeutic efficacy in a CRC mouse model characterized by tumor infiltration of CD8+ T cells and induction of cytotoxic lymphocytes (CTLs) in the spleens.Conclusion: Our findings suggest that PEG-MP9-aPDL1 is an all-in-one platform for oncolytic immunotherapy and immune checkpoint blockade (ICB).

Analysis of allergen components and identification of bioactivity of HSP70 in pollen of Populus deltoides

BackgroundAllergies caused by pollen from Populus deltoides are common, but the allergic components are still unclear.MethodsThe total proteins in pollen of P. deltoides were analyzed by proteomics, and the potential allergens were identified via the WHO/IUIS database and the allergenOnline database retrieval. One target protein was screened by bioinformatics and expressed in Escherichia coli. The biological activity of the expressed product was verified by animal experiments.ResultsThe total of 3929 proteins in pollen of P. deltoides were identified, and 46 potential allergens belonging to 10 protein families were recognized by database retrieval. B9N9W6 protein of Hsp70 family was screened by bioinformatics analysis and expressed successfully. ELISA showed that B9N9W6 can stimulate the immune system to produce specific IgE and promote the generation of IL-4. Flow cytometry showed that B9N9W6 can significantly stimulate the proliferation of CD4+ T cells and promote the polarization of Th2 cells. The pathological sections of mice lung tissues indicated that alveolar destruction was more severe in the B9N9W6 group than that of extract group, and there were more inflammatory cells infiltration, mucus exudation and bleeding.ConclusionB9N9W6 is an important antigenic substance in the pollen of P. deltoides. Due to the conserved structure of Hsp70 family, more attention should be paid to the possibility of sensitization when Hsp70 from any pathogenic species is administered.

ABO Blood Group System and RH Factor

There are many systems which are used to classify blood group types in man, the most common types are MN, ABO and Rh blood group systems. Among the above mentioned types, ABO blood group system is most common which is used to classify blood group types. Austrian immunologist, Karl Landsteiner was the first person to give and describe the system in 1900 [1]. This system explains four types of blood groups which include A, B, AB and O [2]. These blood groups are made on the basis of presence or absence of special proteins found on erythrocytes (red blood cells) which are known as antigens. These antigens are A and B. Antigen production in the body starts before birth of a person and remains throughout life. Antigen production is under control of two genes IA and IB. People whose blood group is A have antigen A in their red blood cells. Persons which have blood group B have antigen B in their red blood cells. AB blood group has both the antigens A and B at the same time while blood group O is due to complete absence of any antigen. In emergency condition, when blood transfusion is required, the blood groups of donor and recipients are cross matched because there can be compatibility issues which can lead to deleterious consequences as red blood cells are attacked. This is due to the production of another type of protein naturally produced in a human body known as antibody. An antibody has capability to agglutinate the antigens found on red blood cells. Thus blood transfusion is a very serious process which needs to be done vigilantly. People who have blood group AB can receive blood from any other type so they are called universal donors. Similarly people with blood group O can donate blood to all types thus are called as universal donors. This blood group is also very common in entire world particularly in people of South and Central America. Blood group B is common in Asia specially North India. Blood group A is equally common in the world specially people of Australian Aboriginal origin. It has been reported that ABO blood group types are also present in Order primates of class mammalia and also in Old World Monkeys [3]. ABO antibodies are passively obtained from mother in children well before birth. Infants of three months age start making their own antibodies. Antibody formation is due to stimulus of contact with ABO like antigenic substances naturally [4].
 The second most common system to classify blood group types is Rh system [5]. This system was given by again Karl Landsteiner and A. S. Weiner in 1940. This type of system is also due to proteins present on red blood cells. Rh blood group system includes 49 defined antigens with 5 most common antigens including c, C, D and E [6]. Rh (D) is the most distinct antigen. It is main determinant of the trait. Rh positive and Rh negative are the two terms which refer only Rh (D). Antibody production due to Rh factor is a cause of hemolytic reaction in fetus and newborns. The name Rh is given due to use of blood of Rhesus monkeys to determine the presence of Rh antigen in basic test. Rh antigen can lead to deleterious effects in a person having blood group Rh negative if both the factors come in contact due to blood transfusion [7].

Advancements in the Field of Vaccines and Immunization

“Vaccines and Immunization” is a global platform to discuss and learn Vaccines and Immunization, Vaccine Preventable Diseases, Plant-Based Vaccines, Types of Immunology, Immunoresearch & Immunotechnology, Autoimmune & Inflammatory Diseases, Immune Diseases, Making a Session Plan, Giving Vaccinations, HIV Vaccines, Vaccines Production and Development, Vaccines for Immune Mediated Diseases, Vaccine Safety & Efficacy. Vaccines are antigenic substance prepared from the causative agent of a disease or a synthetic substitute, used to provide immunity against one or several diseases. Vaccine stimulates the immune system so that it can recognize the disease and protect from future infection.

Food allergies in weaned piglets in experiment and spontaneous occurrence

Food allergies in weaned piglets in experiment and spontaneous occurrence

Immunotherapy for Hepatocellular Carcinoma: Current Advances and Future Expectations.

Primary liver cancer is a common kind of digestive cancers with high malignancy, causing 745,500 deaths each year. Hepatocellular carcinoma is the major pathological type of primary liver cancer. Traditional treatment methods for patients with hepatocellular carcinoma have shown poor efficacy in killing residual cancer cells for a long time. In recent years, tumor immunotherapy has emerged as a promising method owing to its safety and efficacy with respect to delaying the progression of advanced tumors and protecting postoperative patients against tumor relapse and metastasis. Immune tolerance and suppression in tumor microenvironments are the theoretical basis of immunotherapy. Adoptive cell therapy functions by stimulating and cultivating autologous lymphocytes ex vivo and then reinfusing them into the patient to kill cancer cells. Cancer vaccination is performed using antigenic substances to activate tumor-specific immune responses. Immune checkpoint inhibitors can reactivate tumor-specific T cells and develop an antitumor effect by suppressing checkpoint-mediated signaling. Oncolytic viruses may selectively replicate in tumor cells and cause lysis without harming normal tissues. Here, we briefly introduce the mechanism of immunosuppression in hepatocellular carcinoma and summarize the rationale of the four major immunotherapeutic approaches with their current advances.

Dynamics of α-D-mannose carbohydrate-binding sites distribution in rats’ pancreatic structures during the morpho-functional formation

Recently, the pathology of pancreas in children is observed more frequently. Precursors of inflammation development in pancreas are dysfunctional disorders, which include conditions accompanied by changes in pancreatic secretion in the absence of morphological abnormalities. The pancreas is especially sensitive to irritants in the antenatal period of development and during its morpho-functional formation. Placental function insufficiency and prenatal effects of various pathogens on the fetus can cause abnormalities of morphogenesis. The above determines the relevance of the study, which allows ascertaining the features of the fetus pancreas formation in conditions of antigenic nature substances action. The aim – to study the dynamics of α-D-Mannose carbohydrate-binding sites distribution in rats’ pancreatic structures during the morpho-functional formation, using lectin histochemistry analysis. Material and м ethods. Research was conducted on pancreases of white laboratory rats from the day of birth to ninety days of postnatal development. The experimental group of rats was injected intrafetal with an antigenic solution subcutaneously in the interscapular region. Detection of carbohydrate residues of α-D-Mannose was carried out by lens culinaris agglutinin (LCA), which conjugated with horseradish peroxidase. Results. Antigenic action in the antenatal period results to decrease in density of α-D-Mannose residues in pancreatic structures from the first to the third day of postnatal life. From the seventh day and until the fourteenth day the density of LCA receptors in experimental group has increased. From the twenty first until ninetieth days of life the distribution of carbohydrate receptors to LCA in the experimental group was not differ from the control and intact group. Conclusions. The increase in density of carbohydrate residues of α-D-Mannose in pancreatic structures in early postnatal period is the sign of immaturity, which may have the direct effect on secretory activity of organ.

A Unique Triad of Ulcerative Colitis With Autoimmune Hemolytic Anemia and Primary Sclerosing Cholangitis

Inflammatory Bowel Diseases (IBD) lead to chronic intestinal inflammation along with extra-intestinal manifestations which could present prior to, subsequent with or after the diagnosis of IBD. We present a unique case of Ulcerative Colitis (UC), Autoimmune Hemolytic Anemia (AIHA) and Primary Sclerosing Cholangitis (PSC) diagnosed simultaneously in a patient. The unique triad of these diseases gives important clues to the immunological factors involved in the pathogenesis of these diseases. An 18-year-old male presented with 1 week of bloody diarrhea, abdominal cramps and nausea. Vitals were stable. Initial labs showed Hb 9.5 g/dL, MCV 102 fL, WBC 22.4 x 103/μL, total bilirubin 2.4 mg/dL, direct bilirubin 0.7 mg/dL, alkaline phosphatase 436 units/L, ALT 133 units/L and AST 83 units/L. Hepatitis panel and Clostridium difficile toxin assay were negative. Further work-up revealed reticulocyte count > 17%, LDH 529 units/L, haptoglobin < 10 mg/dl and positive direct Coomb's test. Peripheral smear showed hemolysis by a warm antibody. Hydrocortisone was started for AIHA. CT abdomen showed mild colonic wall thickening. Colonoscopy showed moderate pancolitis and biopsies showed findings consistent with UC. Mesalamine was started. MRCP showed irregular beaded appearance of intra and extrahepatic bile ducts. ERCP was performed and biopsies taken from the ducts showed chronic inflammation but no evidence of malignancy. ASMA and ANCA were positive. Liver biopsy ruled out overlap syndrome with autoimmune hepatitis. The patient clinically improved and was discharged to follow-up with a gastroenterologist. In patients with UC, extra-intestinal manifestations involving cutaneous, hepatobiliary and ocular systems are common. The concomitant presence of PSC is 2-7% and AIHA is 0.2 -1.7% in patients with UC. The extra-intestinal manifestations of UC could be due to associated autoimmune diseases or they could be immune-mediated due to damaged mucosal wall. The exact pathogenesis of PSC and AIHA is unknown. The absorption of toxins and antigenic substances from the mucosa in the circulation mediates inflammation in the biliary system leading to PSC. This also leads to warm anti-E antibody production which cross-react with intestinal microbiome and the E antigen at the surface of RBCs. In UC patients, a vigorous workup for early detection of other autoimmune diseases is important to improve the quality of life and to prevent mortality associated with them.Figure: Peripheral smear showing polychromatic RBCs and microspherocytes.Figure: Axial CT demonstrating mild wall thickening and featureless appearance of the rectosigmoid colon compatible with chronic ulcerative colitis (left). Descending colon at 4X magnification showing crypt distortion, cryptitis and crypt abscess (right).Figure: Left: Coronal thin section T2 weighted image showing a beaded appearance of the left hepatic and intrahepatic bile ducts with alternating strictures (arrows) and dilatation (arrowheads). Right: A) Fluoroscopic image from an ERCP depicting beading of the bilateral intrahepatic bile ducts due to segmental strictures (thin arrows). Guidewire in the left intrahepatic bile duct (thick arrow). B) ERCP image after biliary stent placement (arrowhead) with decompression of the biliary tree.